Final Program Syllabus - MCJ Consulting

January 27, 2012
Dear Colleagues,
On behalf of the Santa Monica Sports Medicine Foundation and Kerlan Jobe Orthopedic
Foundation, we are pleased to welcome you to the 12 th International Sports Medicine Fellows
Conference: Comprehensive Approaches to Articular Cartilage Repair and Hip Arthroscopy, to
Carlsbad, California.
This two day meeting includes a variety of lectures on topics related to Articular Cartilage
Repair and Hip Arthroscopy. Hands-on labs will serve to enhance your educational experience.
We hope you take the time to enjoy the beautiful California coast, with its natural beauty and
variety of activities.
The 12 th Annual International Sports Medicine Fellows Conference will be successful as we
welcome fellows from around the country, hungry for information related to the practice of
sports medicine.
Best Regards,
Bert R. Mandelbaum, MD
Course Chairman
Medical Director, Santa Monica Orthopaedic and Sports Medicine Group
Ralph A. Gambardella, MD
Course Chairman
Medical Director, Kerlan Jobe Orthopaedic Clinic
ISMF Program Office: MCJ Consulting ● 2678 Bishop Drive ● Suite 250 ● San Ramon, California USA ● Tel +1 (925) 807 1190

12 th International Sports Medicine Fellows Conference:
Comprehensive Approaches to Articular Cartilage Repair and Hip Arthroscopy
January 27-29, 2012 • Carlsbad, California
The 12 th International Sports Medicine Fellows Conference gratefully
acknowledges the generous support of:
Platinum Sponsors:
Gold Sponsors:
Silver Sponsors:

12 th International Sports Medicine Fellows Conference:
Comprehensive Approaches to Articular Cartilage Repair and Hip Arthroscopy
January 27-29, 2012 • Carlsbad, California
Wayne K. Augé II, MD
Fall River, MA, USA
Robert H. Brophy, MD
Chesterfield, MO, USA
William Bugbee, MD
La Jolla, CA, USA
J.W. Thomas Byrd, MD
Nashville, TN, USA
Susan Chubinskaya, PhD
Chicago, IL, USA
Brian J. Cole, MD
Chicago, IL, USA
Jack Farr, MD
Greenwood, Indiana, USA
Wayne K. Gersoff, MD
Denver, CO, USA
Alberto Gobbi, MD
Milan, ITALY
Course Chairs:
Bert R. Mandelbaum, MD, Course Co-Chair
Santa Monica, California, USA
Ralph A. Gambardella, MD, Course Co-Chair
Los Angeles, California, USA
Michael B. Gerhardt, MD, Hip Course Chair
Manhattan Beach, California, USA
Course Faculty
William Hutchinson, MD
Santa Monica, CA, USA
Warren Kramer, MD
Newport Beach, CA, USA
David R. McAllister, MD
Los Angeles, CA, USA
Kai Mithoefer
Boston, MA, USA
Marc Safran, MD
Redwood City, CA, USA
Robert L. Sah, MD, ScD
La Jolla, CA, USA
Jason M. Scopp, MD
Salisbury, Maryland, USA
Jason Snibbe, MD
Beverley Hill, CA, USA
Jason Theodosakis, MD
Tucson, AZ, USA
C. Thomas Vangsness, MD
Los Angeles, CA, USA

Driving Directions from Hilton Garden Inn to DJO Inc.
Start: Hilton Garden Inn Carlsbad Beach
6450 Carlsbad Blvd
Carlsbad, CA 92011
(760) 476-0800
End: DJO Incorporated
1430 Decision Street
Vista, CA 92081
Directions Distance Time
Start: Drive (West) toward Carlsbad Blvd. 0.2 0:01
1: Turn RIGHT to merge onto Palomar Airport Rd [CR-S12] 6.3 0:07
2: Turn LEFT (North) onto Business Park Dr. 0.6 0:01
3: Take 2 nd RIGHT (North-East) onto Scott St 0.1 0:01
4: Take 1 st RIGHT (South) onto Decision St < 0.1 0:01
End: Arrive (DJO Inc) 1340 Decision Street is on the RIGHT < 0.1 < 1min
Total Route (approximate-driving times vary) 7.1 mi 11 mins
If you have problems getting into the lab call:
Cheresse Edwards, CERF Coordinator
760-597-3942 office
760-535-4704 cell - Best number to reach her

12 th International Sports Medicine Fellows Conference
January 27-29, 2012● Carlsbad, California
Session I
7:15 AM - 7:30 AM Basics of Articular Cartilage/Repair Robert Sah, MD, ScD USA
7:30 AM - 7:45 AM Articular Cartilage Imaging: New Horizons Robert Brophy, MD USA
7:45 AM - 8:00 AM Microfracture Kai Mithoefer, MD USA
8:00 AM - 8:15 AM Medium and Small Defects OC AutoGrafts and New Scaffolds Ralph Gambardella, MD USA
8:15 AM - 8:30 AM CAIS and Juvenile Allogenic Cells Clinical Trials Bert Mandelbaum, MD USA
8:30 AM - 8:45 AM Osteochondral Allograft: Basic Science William Bugbee, MD USA
8:45 AM - 9:00 AM Osteochondral Allograft: Clinical Experience David McAllister, MD USA
9:00 AM - 9:15 AM Discussion

Basics of Articular Cartilage & Synovial Joints
11 th Annual Articular Cartilage Repair Course
for Sports Medicine Fellows
January 15, 2011
Robert L. Sah, MD, ScD
Professor of Bioengineering &
Adjunct Professor of Orthopaedic Surgery
University of California, San Diego
La Jolla, California 92093-0412
Professor,
Howard Hughes Medical Institute
rsah@ucsd.edu

Articular Cartilage Repair Course for Sports Medicine Fellows Robert L. Sah, MD, ScD
Basics of Articular Cartilage & Synovial Joints January 16, 2011
OUTLINE
1) Principles of load-bearing, low-friction, and wear-resistant biomechanical functions of
articular cartilage in healthy synovial joints.
� Articular cartilage bears load that is >NxBW, over contact areas of ~(cm) 2 , with
corresponding stress levels of ~MPa.
� Normally, articular cartilage (synovial joints) has an apparent friction coefficient, μ, of
~0.001-0.05 that varies markedly with the method of measurement.
� Normally, articular cartilage (synovial joints) has a wear coefficient, κ, of ~0.001 (μm) 2 /N.
2) The basis of the biomechanical functions of cartilage and synovial joints.
� The load-bearing properties of articular cartilage exhibit visco(poro)-elasticity.
o Under compressive loading, normal cartilage becomes pressurized with little
compressive strain, and then slowly depressurizes as fluid exudes out and
compressive strain increases.
o The content and organization of its matrix constituents, especially proteoglycan and
collagens, contribute to high compressive modulus and low hydraulic permeability.
o In osteoarthritis, the balance between proteoglycan swelling and collagen restraint is
altered due to collagen network dysfunction, resulting in cartilage swelling.
� The low-friction properties of articular cartilage are due to pressure-dependent and pressureindependent
phenomena (intrinsic friction coefficient with normal synovial fluid is 0.025).
o In the boundary mode of lubrication, the low-friction properties of cartilage are
dependent on the lubricating effects of synovial fluid (Schmidt+, Osteoarthritis
Cartilage, 2007) and lubricant molecules, proteoglycan-4 (aka lubricin, superficial
zone protein, PRG4) and hyaluronan (Schmidt+, Arthritis Rheum, 2007).
o The “intrinsic” (boundary-mode) steady-state friction coefficient of articular cartilage,
lubricated with normal synovial fluid, is ~0.025 (Schmidt+, Osteoarthritis Cartilage,
2007).
o The boundary lubricants in synovial fluid normally serve to lower cartilage-cartilage
friction, and, consequently, shear strain of cartilage during loading.
o After injury, synovial fluid is deficient in lubricating properties (Elsaid+, Arthritis
Rheum, 2005), in association with decreased hyaluronan (Ballard+, JBJS, 2012)
and/or PRG4 (Jay+, Arthritis Rheum, 2007).
� The wear-resistance of cartilage depends on synovial fluid components, probably also
boundary lubricant molecules.
p. 2

Articular Cartilage Repair Course for Sports Medicine Fellows Robert L. Sah, MD, ScD
Basics of Articular Cartilage & Synovial Joints January 16, 2011
3) The biological and biophysical basis of articular cartilage maintenance and repair.
� Heterogeneity in the Cells and Matrix of Articular Cartilage and Synovial Tissues.
o The chondrocytes within articular cartilage are heterogeneous.
1. Cells in the superficial zones synthesize and secrete large amounts of
proteoglycan-4 lubricant (Flannery CR+, BBRC, 1999), whereas cells in the
middle and deep zones synthesize and secrete large amounts of aggrecan.
Don’t let the articular cartilage surface dry out (killing the surface chondrocytes) during
surgery.
2. Progenitor cells within cartilage and surrounding tissues may be sources for
repair.
o The matrix of articular cartilage is heterogeneous and anisotropic.
1. The tangentially-oriented collagen network of the superficial zone provides
high tensile stiffness (Temple MM+, Osteoarthritis Cartilage, 2007) and
resistance to wear.
2. The aggrecan content of the middle and deep zones provides high
compressive stiffness and low hydraulic permeability (Chen AC+, J
Biomechanics, 2001).
3. The depth-variation in aggrecan content, in association with collagen network
content and function (Han EH+, Biophys J, 2011), underlies the depth-varying
compressive modulus of articular cartilage (Schinagl RM+, J Orthop Res,
1997)
� Mechanobiological Homeostasis of Load-Bearing.
o The dynamics of load-bearing proteoglycan and collagen molecules in cartilage
extracellular matrix depends (Hascall and Sandy) on the balance between
1. synthesis and secretion by chondrocytes
2. degradation by enzymes and loss driven by fluid flow.
o Articular cartilage responds to dynamic compression (Sah RL+, J Orthop Res, 1989)
and shear (Jin M+, Arch Biochem Biophys, 2001) via chondrocyte altering synthesis
of matrix constituents, important for load-bearing.
o Excessive compression can induce lethal strains to the chondrocytes.
Be gentle with articular cartilage. Do not poke it or whack it too hard.
� Mechanobiological Homeostasis of Articulation.
o The dynamics of lubricant molecules in synovial fluid depends (Blewis ME+., Eur
Cell Mater, 2007) on the balance between
1. the cells lining the synovial joint, the chondrocytes and synoviocytes,
secreting proteoglycan-4 and hyaluronan lubricant into synovial fluid
2. degradation/loss of lubricant molecules from synovial fluid.
p. 3

Articular Cartilage Repair Course for Sports Medicine Fellows Robert L. Sah, MD, ScD
Basics of Articular Cartilage & Synovial Joints January 16, 2011
o Articular cartilage responds to dynamic shear via chondrocytes in superficial zone
altering synthesis of PRG4 lubricant into the synovial fluid (Nugent GE+, Arthritis
Rheum, 2006).
o PRG4 lubricant molecules are absorbed to the articular surface through interactions
allowing it to be depleted and then repleted (Nugent GE+, J Orthop Res, 2007).
o Continuous passive motion (of knee joints ex vivo) enhances secretion of PRG4
(Nugent-Derfus GE+, Osteoarthritis Cartilage, 2007).
p. 4

ARTHRITIS & RHEUMATISM
Vol. 58, No. 7, July 2008, pp 2065–2074
DOI 10.1002/art.23548
© 2008, American College of Rheumatology
Biomechanics of Cartilage Articulation
Effects of Lubrication and Degeneration on Shear Deformation
Benjamin L. Wong, 1 Won C. Bae, 1 June Chun, 1 Kenneth R. Gratz, 1
Martin Lotz, 2 and Robert L. Sah 1
Objective. To characterize cartilage shear strain
during articulation, and the effects of lubrication and
degeneration.
Methods. Human osteochondral cores from lateral
femoral condyles, characterized as normal or
mildly degenerated based on surface structure, were
selected. Under video microscopy, pairs of osteochondral
blocks from each core were apposed, compressed
15%, and subjected to relative lateral motion with
synovial fluid (SF) or phosphate buffered saline (PBS)
as lubricant. When cartilage surfaces began to slide
steadily, shear strain (E xz) and modulus (G) overall in
the full tissue thickness and also as a function of depth
from the surface were determined.
Results. In normal tissue with SF as lubricant, E xz
was highest (0.056) near the articular surface and
diminished monotonically with depth, with an overall
average E xz of 0.028. In degenerated cartilage with SF as
lubricant, E xz near the surface (0.28) was 5-fold that of
normal cartilage and localized there, with an overall E xz
of 0.041. With PBS as lubricant, E xz values near the
articular surface were �50% higher than those observed
with SF, and overall E xz was 0.045 and 0.062 in normal
and degenerated tissue, respectively. Near the articular
Supported by the National Science Foundation and the NIH.
Mr. Wong’s work was supported in part by the San Diego Fellowship.
Dr. Sah’s work was supported by the Howard Hughes Medical Institute
through the Professors Program Grant to the University of California,
San Diego.
1 Benjamin L. Wong, MS, Won C. Bae, PhD, June Chun, BS,
Kenneth R. Gratz, MS, Robert L. Sah, MD, ScD: University of
California, San Diego, La Jolla, California; 2 Martin Lotz, MD: Scripps
Research Institute, La Jolla, California.
Mr. Wong and Dr. Bae contributed equally to this work.
Address correspondence and reprint requests to Robert L.
Sah, MD, ScD, Department of Bioengineering, Mail Code 0412,
University of California, San Diego, 9500 Gilman Drive, La Jolla, CA
92093-0412. E-mail: rsah@ucsd.edu.
Submitted for publication September 20, 2007; accepted in
revised form March 18, 2008.
2065
surface, G was lower with degeneration (0.06 MPa,
versus 0.18 MPa in normal cartilage). In both normal
and degenerated cartilage, G increased with tissue
depth to 3–4 MPa, with an overall G of 0.26–0.32 MPa.
Conclusion. During articulation, peak cartilage
shear is highest near the articular surface and decreases
markedly with depth. With degeneration and diminished
lubrication, the markedly increased cartilage
shear near the articular surface may contribute to
progressive cartilage deterioration and osteoarthritis.
The tissue-scale mechanics of articular cartilage
during the compressive and shear loading of joints with
normal movement have not been fully characterized.
After repeated knee bending (1) and running (2), articular
cartilage is compressed by �5–20% of its overall
thickness. Within the cartilage tissue of dynamically
compressed osteochondral blocks (3), the magnitude of
compressive strain is highest near the articular surface
and minimal in deeper regions, a pattern consistent with
the depth-varying compressive modulus of cartilage (4).
Despite extensive knowledge of cartilage compressive
behavior, the overall and depth-varying shear deformation
of cartilage during joint movement remains to be
elucidated. Theoretical models of articulating joints can
be used to predict local cartilage deformation (5,6), but
are highly dependent on assumptions about boundary
conditions at articulating surfaces (e.g., frictionless or
adherent) and depth-varying mechanical properties (5).
Detailed experimental characterization of apposing cartilage
samples sliding relative to one another would
further the understanding of cartilage mechanics during
joint movement by elucidating the actual boundary
condition at the articulating cartilage surface as well as
the deformation and properties of cartilage in shear.
Lubrication of articulating cartilage by synovial
fluid (SF) facilitates low friction in the boundary mode

2066 WONG ET AL
and may therefore affect the shear deformation of
cartilage. When articulating cartilage is tested in a
configuration that reveals boundary lubrication effects,
SF and lubricant molecules in SF are shown to reduce
articular surface interaction, as indicated by decreased
friction (7,8). The replacement of SF lubricant with
phosphate buffered saline (PBS) results in an elevation
of boundary-mode friction (7). The dependence of local
and overall shear deformation on SF may be important
for maintenance of cartilage health, since acute injury or
inflammatory arthritis results in reduced lubricating
function of SF, and this may be involved in postinjury
cartilage degeneration (9).
Cartilage degeneration may also affect the way in
which the tissue deforms during joint movement. As
cartilage undergoes degeneration, for example with aging
(10), articular surfaces become fibrillated and roughened
(11). Concomitantly, cartilage mechanical properties
deteriorate under compressive, tensile, and shear
loading (12), i.e., cartilage deformation and strain magnitude
increase in response to a particular amplitude of
applied load. Such mechanical deformation of cartilage
affects chondrocyte metabolism, with moderate levels of
dynamic compressive and shear strain stimulating matrix
synthesis, but excessive levels inhibiting matrix synthesis
(13). Thus, determination of the deformation and strain
of articulating cartilage, with both normal and degenerated
surfaces, would provide insight into the local mechanical
cues that regulate chondrocyte behavior and
the consequences of degenerative changes on such cues.
One experimental approach used to elucidate the
local strain deformation and strain of cartilage is to track
displacement of fiducial markers using a video microscopy
system. Previous studies have focused on cartilage
deformation and strain when samples were subjected to
compression in the absence of applied shear (4,14,15).
The depth-dependent compressive behavior of cartilage
found in these microscale studies was consistent with
findings in macroscopic tissue explants investigated by
magnetic resonance imaging (3), and provided a resolution
sufficient to resolve small magnitudes of strain
(�1%). Thus, microscale analysis may also provide
insight into cartilage shear deformation, both locally and
overall. For studying cartilage shear deformation during
joint movement (Figure 1A), a pair of osteochondral
blocks (Figure 1B) can be compressed in apposition
(Figure 1C) and subjected to lateral shearing motion
(Figure 1D). Such a configuration can be controlled to
mimic the biomechanical behavior of articulating cartilage
at one scale (full-thickness tissue) and allow elucidation
of cartilage deformation at a finer scale (regions
Figure 1. A and B, Schematic representation of knee joint movements
at multiple scales (A), and deformation of cartilage under no load,
compression (Comp.), and compression plus shear loading (B). C,
Material points in compressed cartilage before and during shear
loading used to determine u�(x,z) (depth-dependent displacement
[Disp.] vectors), which were then used to assess intratissue deformation.
D, Schematic representation of experimental setup and loading
protocol for microscale shear testing.
of tissue measurements). Combined measurements of
strain and stress allow determination of local and overall
biomechanical properties such as shear modulus.

LUBRICATION AND DEGENERATION EFFECTS ON CARTILAGE SHEAR DURING ARTICULATION 2067
Table 1. Age of the donors, and thickness and Mankin-Shapiro
scores of the cartilage samples*
Normal
(n � 3)
The hypothesis of the present study was that
during joint articulation, the shear deformation of cartilage
is affected by both lubrication and degeneration.
To test this, we implemented a cartilage-on-cartilage
sliding test to microscopically observe and analyze cartilage
deformation during compression and shear. With
this system, we assessed the effects of lubrication (by SF
versus PBS) and degeneration (normal versus mildly
degenerated) on overall and depth-varying shear strain,
and determined the overall and depth-varying shear
modulus of normal and mildly degenerated cartilage.
MATERIALS AND METHODS
Mildly degenerated
(n � 3)
Age, years 48 � 1.7 78 � 9.2
Thickness, mm 1.86 � 0.12 2.08 � 0.15
Mankin-Shapiro score 1.89 � 0.29 9.11 � 1.24
* Values are the mean � SEM.
Sample isolation. Osteochondral cores (each with a
diameter of 10 mm) were isolated from the anterior lateral
femoral condyle of a single knee block from each of 6 fresh
human cadaveric tissue donors (Table 1). Cores were chosen
for this study based on the gross appearance of the articular
surface, i.e., normal (n � 3) or mildly degenerated (n � 3). The
surface was considered normal if the modified Outerbridge
grade (16) was 1, and mildly degenerated if the grade was 3.
Normal specimens were from donors ages 41–60 years at the
time of death, and degenerated specimens were from donors
age �60 years (Figures 2A and B). The cores were immersed
in PBS containing proteinase inhibitors (PIs) and stored at
�80°C until use.
Experimental design. On the day of testing, each core
was thawed and prepared. The core was scored vertically in the
cartilage using a razor blade and cut through the bone using a
low-speed saw with a 0.3-mm–thick diamond-edge blade
(Isomet; Buehler, Lake Bluff, IL) to yield an osteochondral
fragment for histopathologic analysis and 2 approximately
rectangular blocks for biomechanical testing. Each of the 2
blocks had a cartilage surface area of �3 � 8mm 2 and a total
thickness of �7 mm.
Histopathologic analysis. Histopathologic analysis was
performed to assess and confirm the state of degeneration.
Samples were fixed in 4% paraformaldehyde in PBS (pH 7.0)
for 24 hours, decalcified with 18% disodium EDTA in PBS for
7 days, and sectioned to 7 �m using a cryostat. Some sections
were stained with Alcian blue to localize sulfated glycosaminoglycans
(GAGs), as previously described (17), and other
sections were stained with hematoxylin and eosin to highlight
cellular detail (18). Staining of samples resulted in a gradation
of intensity (Figures 2C and D), reflecting the variation in
GAG concentration with depth; thus, the staining method was
sufficient to delineate GAG variation, such as loss due to
pathology, and allow qualitative scoring. Transmitted light
micrographs of the stained sections were obtained, and histologic
features (19) analyzed using the Mankin-Shapiro semiquantitative
scale (20). Briefly, the histopathologic characteristics
assessed included structural integrity (surface irregularity
and vertical and horizontal clefts), cellularity (cloning and
hypocellularity), and GAG loss. A relatively high score represented
more degenerated cartilage. Grades from 3 independent
observers were averaged for each sample. Interobserver
errors (SD) for normal and degenerated samples were reasonably
small (average 1.0 and 2.1, respectively).
Biomechanical testing. Samples were first tested by
microscale shear testing as described below, with PBS plus PI
as the lubricant. Then, samples were allowed to reswell for �4
hours at 4°C.
Next, samples were tested again by microscale shear
Figure 2. A and B, Photographs of cross-sections of samples of
normal and degenerated cartilage. C and D, Representative micrographs
of Alcian blue–stained sections, showing structure detail of
normal (C) and degenerated (D) cartilage. Color figure can be viewed
in the online issue, which is available at http://www.arthritisrheum.org.

2068 WONG ET AL
testing, this time with SF (pooled from adult bovine knees and
stored at �80°C) plus PI as the lubricant. The SF had been
characterized previously for boundary lubrication properties
(7) and for levels of lubricant molecules (�1 mg/ml of hyaluronan
and 0.45 mg/ml of proteoglycan 4 [21]). The same
regions of interest as used in studies with PBS were imaged.
Then, samples were allowed to reswell.
Finally, samples were tested in a macroscale shear
system to assess overall mechanical properties of cartilage in
shear, as described below.
Microscale shear testing. Each sample, consisting of
paired osteochondral blocks, was bathed for �14–18 hours in
test lubricant containing PI and propidium iodide (20 �g/ml) at
4°C to fluorescently highlight cell nuclei prior to microscale
shear testing. Each pair of osteochondral blocks (Figures 1B
and D) was then placed with cartilage in apposition in a custom
biaxial loading chamber mounted onto an epifluorescence
microscope for digital video imaging (4). The chamber secured
one block at the bone and allowed in-plane movement of the
apposing mobile block along the x-directed 8-mm lengths of
the samples (Figure 1D), with orthogonally positioned plungers
interfaced with either a micrometer (for axial displacement)
(model 262RL; Starrett, Athol, MA) or motioncontroller
(for lateral displacement) (model MFN25PP;
Newport, Irvine, CA). Fluorescence images (G-2A filter; Nikon,
Melville, NY) with a field of view of �3 � 2mm 2 were
obtained at 5 frames/second, showing a full-thickness region of
cartilage in the secured block and a partial-thickness region of
cartilage in the apposing block.
Cartilage deformation in the secured block was assessed
during axial and shear loading. First, the block was
imaged in the reference state (uncompressed). Then, axial
displacement (�40 �m/second) was applied by the micrometer
to induce 15% compression (1 �� z, where � z is the stretch
ratio [22]) of the cartilage tissue (Figure 1C), during which
time sequential images (�1.5% compression increment/frame)
were acquired. Samples were then allowed to stress-relax for 1
hour, which was calculated to be sufficient to reach an approximate
equilibrium stress based on consideration of the characteristic
time constant. Experimentally, this duration of stressrelaxation
was validated to be sufficient with load decreasing to
50% of the peak by 130 seconds, and load at 1 hour being only
3 � 1% (mean � SEM; n � 3) higher than the load at 16
hours. Subsequently, lateral motion was applied to the mobile
osteochondral block (Figure 1D). Two sets of lateral displacements
(�x), each consisting of �1 mm and then �1 mm
(returning to initial position), were applied at 100 �m/second
to the bone portion of the mobile block. The first set, followed
by a pause of 12 seconds, was for preconditioning (7), while the
second set was recorded for analysis. The sliding velocity was
chosen based on the range of velocities (0–0.1 m/second)
occurring during the loading (stance) phase of gait (23,24).
Before and during the application of lateral displacements
(Figure 1D), sequential images, with �10 �m of lateral
movement of the mobile block between frames, were obtained.
Macroscale shear testing. To assess the overall compressive
and shear biomechanical properties of the cartilage of the
secured block, following microscale shear tests, each secured
block was subjected to a macroscale test using a biaxial
mechanical tester (Mach-1 V500CS; BioSyntech, Montreal,
Quebec, Canada). Test conditions were chosen to match the
mechanical deformation observed in the microscale shear test,
but with instrumentation allowing measurement of axial and
shear loads. Each sample block was affixed, compressed 15%
at a rate of 0.03%/second using a rigid stainless steel platen
(�2 �m pore size, providing a no-slip boundary condition),
and allowed to stress-relax for 1 hour to reach equilibrium.
With increasing lateral displacement, continuous and monotonically
increasing shear load waveforms were observed,
confirming no-slip conditions; a plateau in shear load, which
would indicate slip, was not observed. Equilibrium force was
recorded and normalized to the 3 � 8mm 2 area to yield an
estimate of the equilibrium compressive stress. Next, 2 sets of
lateral displacements of the amplitude occurring at the surface
at the onset of sliding in microscale shear tests were applied at
a rate of 100 �m/second, held for 10 seconds while shear load
was being recorded, and released. A pause of �12 seconds
followed the first set of lateral displacements, during which the
cartilage sample was continuously hydrated in PBS plus PI. As
in the microscale tests, the first set was for preconditioning,
while the second set was used for analysis. The lateral displacements
were then repeated in the reverse direction following a
5-minute pause, and shear loads occurring in the last second of
the 10-second load-capture period in both directions were
averaged. This average shear load was normalized to the 3 �
8mm 2 area to yield an estimate of the shear stress (at which
sliding occurred in the microscale test).
Data collection and calculations. Digital micrographs
were analyzed to determine the depth-varying and overall
strains in cartilage. Images were analyzed with MatLab 7.0
(MathWorks, Natick, MA) using software routines similar to
those described previously (14,25,26). Briefly, an evenly distributed
set of cell nuclei (�250 cells/mm 2 ), which served as
fiducial markers, was selected and tracked by maximizing
cross-correlation of regions surrounding each marker with the
preceding, and then initial, frames. Generally, chondrocyte
nuclei in normal tissue were available, and were chosen in
regions up to the true articular surface (defined by a discontinuity
in displacement during sliding), while for degenerated
tissue, nuclei were visible up to �50–70 �m (�3%) below the
true surface, due to fibrillation. Local affine mappings of
nuclei were used to calculate the displacement (u�) of uniformly
spaced (10-pixel) mesh points in the region of interest (�1
mm � full thickness) during deformation (Figure 1D). Displacement
gradients (�u�/�z, �u�/�x) were then determined by
finite difference approximations, and in turn, used to determine
Lagrangian compressive strain (E zz) after axial compression
and shear strain (E xz) after lateral shearing, with these
Lagrangian strains being appropriate for finite strains as well
as small strains (27).
This method was validated, and interobserver variability
was assessed. Using mathematically transformed images,
the calculated strain values deviated by less than 0.005 � 0.005
(mean � SEM) from the theoretical values, with the error
being proportionately smaller in regions exhibiting lower amplitudes
of strain. Interobserver variability, assessed as the
average of the SD in calculated strain between 3 observers, was
�0.01 for a subset of data from all sample types (n � 4). Here

LUBRICATION AND DEGENERATION EFFECTS ON CARTILAGE SHEAR DURING ARTICULATION 2069
also, the variability was proportionately lower in regions of
relatively small shear magnitudes.
The calculated shear strain was interpolated, averaged
depthwise, and plotted as a function of tissue depth, normalized
to the cartilage thickness in the compressed state. Shear
strain was interpolated linearly at every 5% of the normalized
tissue thickness near the articular surface (i.e., 0–0.3) and
every 10% for remaining regions of the tissue depth (i.e.,
0.3–1) after applied compression and prior to lateral motion.
To consolidate data, strain values were averaged at the same
normalized depth (0 [surface] and 1 [tidemark]) to yield a
depth profile. Shear strain results were determined when
surfaces were sliding, at which time shear strain was at a peak
and no further changes in deformation occurred with additional
lateral displacement (i.e., sliding). The overall Lagrangian
shear strain was defined as half the lateral surface displacement
normalized to the compressed cartilage thickness. Since
the shear strain peaked near the articular surface, shear strain
occurring at the top 5% was also compared.
Overall cartilage properties were determined from
forces recorded during compression and shear. Under compression
alone, the compressive modulus of cartilage was
defined as the increment in stress divided by the increment in
applied compressive strain. The overall shear modulus (G) for
each sample was determined as the increment in shear stress
(shear load divided by surface area) divided by the increment
in shear strain.
The depth-varying shear moduli were estimated from
the overall shear modulus and local shear strain in each
sample. Since shear modulus is inversely related to shear
strain, and with shear stress assumed to be constant at all
depths, the local shear modulus was estimated as the overall
shear modulus multiplied by the overall shear strain and
divided by the local shear strain. Because these estimates
depend on shear strain in the denominator, shear modulus was
calculated at every 10% of the tissue depth near the articular
surface (up to 20% of the depth) and every 20% of the tissue
depth in the subsequent regions, to reduce noise.
Statistical analysis. Data are reported as the mean �
SEM, unless noted otherwise. Repeated-measures analysis of
variance was used to determine the effects of normalized tissue
depth (0–1 [surface–bone]), lubricant (PBS or SF), and degeneration
(normal or degenerated) on tissue shear strain, and to
determine the effects of tissue depth and degeneration on
shear modulus.
RESULTS
Histopathologic findings. The overall histopathology
scores were consistent with the gross (Figures
2A and B) and histologic (Figures 2C and D) appearance
of normal and degenerated samples. Degenerated
samples had significantly (P � 0.01) higher histopathology
scores than normal samples (Table 1). In degenerated
samples, structural (surface irregularity, vertical
clefts to transitional zone, and transverse clefts) and
cellular (cloning) features exhibited mild degeneration
and were scored �1-point higher than the corresponding
features in normal samples. In contrast, cellularity
and GAG staining scores were similarly low (i.e., normal)
in normal and degenerated samples. These results
confirmed that gross visualization resulted in an appropriate
selection of normal and mildly degenerated samples,
for articulation testing.
Compressive deformation and properties. The
axial compression of cartilage in the secured block
resulted in compressive strain that varied significantly
with depth from the articular surface (P � 0.001) but not
between normal and degenerated samples (P � 0.6). E zz
was relatively high near the articular surface (mean �
SEM 0.38 � 0.05) and relatively low in the deepest
regions (0.06 � 0.01). Transverse-oriented (E xx) and
shear (E xz) strain resulting from the applied compression
was low, averaging �0.03 in all samples. The
equilibrium compressive modulus (E) in the fullthickness
cartilage was not significantly different between
sample groups (P � 0.5) (mean � SEM 0.79 �
0.13 MPa in normal cartilage and 0.61 � 0.23 MPa in
degenerated cartilage).
Shear deformation. Qualitatively, cartilage shear
loading resulted in a sequence of 4 events: 1) At the
onset of applied lateral displacement, cartilage surfaces
initially adhered and began to move laterally in unison.
2) With increasing lateral displacement, lateral deformation
and hence E xz increased and occurred throughout
the tissue depth. 3) Next, lateral deformation and E xz of
cartilage peaked, just as the surfaces detached and slid
relative to each other. 4) With additional lateral displacement,
the cartilage deformation and E xz were
maintained at a steady-state peak.
At the steady state, tissue displacement and E xz
(Figure 3) were nonuniform and depth-varying, with
shear magnitudes that were high near the articular
surface and low (almost indistinguishable) near the
bone. The mean � SEM maximum lateral displacement
of apposing surfaces before slipping when lubricated
with SF was 115 � 14 �m and 82 � 16 �m in normal and
degenerated tissue, respectively. When lubricated with
PBS, maximum lateral displacement in normal and
degenerated tissue was 169 � 12 �m and 125 � 18 �m,
respectively, before slipping. Differences in shear deformation
between normal and degenerated samples were
also evident (Figure 3). Shear deformation in degenerated
samples (Figures 3C and D) was concentrated near
the surface, while in normal samples, deformation occurred
further into the tissue depth (Figures 3A and B).
Quantitatively, the E xz of articulating cartilage

2070 WONG ET AL
Figure 3. Micrographs obtained during shear loading of apposing
normal (A and B) and degenerated (C and D) cartilage samples
lubricated with phosphate buffered saline (PBS) (A and C) or synovial
fluid (SF) (B and D), after maximum shear strain was achieved. The
cell nuclei tracking method was used to create maps of shear strain
(magnified above each panel; boxes with dotted lines indicate magnified
areas). Dashed lines surround the analyzed regions on the
undeformed images. Schematic at the bottom depicts the sample and
testing configuration, with the dotted-line box representing the area
from which the images shown were obtained and analyzed. Bars � 100
�m.
varied with depth from the articular surface, lubricant,
and surface degeneration. In the depth profile of E xz
(Figures 4A and B), the highest values were obtained
near the articular surface, and E xz decreased monotonically
with depth (P � 0.001). The variation of E xz with
depth depended on surface degeneration (P � 0.001 for
the interaction), with E xz decreasing more with depth in
the degenerated sample. A similar trend was noted with
testing using PBS, where E xz decreased at greater rates
with depth than when tested with SF (P � 0.001 for the
interaction) in both normal and degenerated samples.
The combined effect of depth and either degeneration
or lubricant on shear strain was evidenced as varying E xz
values near the surface, but similarly low values of E xz
(�0.01) in the deep layer of cartilage.
Peak E xz at the surface (z � 0) (Figure 5A) and
overall E xz (Figure 5B) were each significantly affected
by both the lubricant used and degeneration status. The
peak surface E xz (Figure 5A) was �3–5 times higher in
Figure 4. Biomechanical measures of adult human articular cartilage
in shear. A and B, Local shear strain (E xz) versus normalized tissue
depth in normal and degenerated cartilage, as determined by microscale
shear testing. Samples were tested with phosphate buffered
saline (PBS) (A) or synovial fluid (SF) (B) as lubricant. C, Local shear
modulus (G) versus normalized tissue depth in normal and degenerated
samples, as determined by macroscale testing. Values are the
mean and SEM.

LUBRICATION AND DEGENERATION EFFECTS ON CARTILAGE SHEAR DURING ARTICULATION 2071
Figure 5. Effect of sample group (normal or degenerated cartilage)
and of lubricant (phosphate buffered saline [PBS] or synovial fluid
[SF]) on A, peak surface shear strain and B, overall shear strain. Values
are the mean and SEM.
samples with surface degeneration than in normal tissue
(P � 0.05) with both surface lubricants. With PBS, the
mean of the peak surface (Figure 5A) E xz increased
from 0.11 (normal samples) to 0.41 (degenerated samples).
With SF, E xz increased from 0.056 (normal samples)
to 0.28 (degenerated samples). In addition, peak
surface E xz values obtained when tested with PBS were
�1.5–2 times the values obtained when tested with SF
(P � 0.05). Overall E xz (Figure 5B) was not detectably
different between normal and degenerated samples (P �
0.10) when tested using the same lubricant. However,
overall E xz did vary with lubricant. The overall E xz of
normal tissue was significantly lower with SF than with
PBS (0.028 versus 0.045), and the overall E xz of degenerated
tissue was 0.041 with SF versus 0.062 with PBS (P
� 0.05 for both).
Shear properties. To replicate sample shear deformation
in microscale shear tests, lateral surface dis-
placements in macroscale shear tests ranging from 70 to
125 �m (measured from microscale shear tests) were
applied to normal samples, and 120–160 �m was applied
to degenerated samples. Overall G was not significantly
different between normal and mildly degenerated tissue
(mean � SEM 0.32 � 0.09 MPa in normal and 0.26 �
0.07 MPa in degenerated cartilage; P � 0.7). G was
lowest near the articular surface and increased significantly
with tissue depth (P � 0.01) (0.2–-0.6 times and
10–15 times the overall G near the surface and in the
deepest region, respectively) (Figure 4C). At all depths
below the surface, G was not significantly different
between normal and degenerated samples (P � 0.5).
Near the articular surface, there was a trend toward
lower G values with mild surface degeneration (P �
0.10) (surface G � 0.18 � 0.06 MPa and 0.06 � 0.02
MPa in normal and degenerated samples, respectively).
DISCUSSION
This study elucidated the shear deformation and
strain of cartilage during contact and sliding, as well as
the effects of lubrication and mild degeneration, using a
microscale cartilage-on-cartilage testing system. The
present results indicate that cartilage–cartilage articulation
results in 4 sequential events: adherence, adherence
and deformation, detachment, and sliding. Peak E xz was
highest near the surface and modulated by both the
lubricant used and the condition of the sample itself
(Figures 4A and B). Relative to the use of normal SF as
lubricant, E xz increased with the use of PBS by �100%
near the surface (Figure 5A) and �55% overall (Figure
5B). In addition, when degenerated samples were tested,
their E xz values near the surface were �3–5 times higher
than those of normal samples (Figure 5A).
Osteochondral samples used in this study were
prepared from a site that is affected by age-associated
degeneration and osteoarthritis. The samples were from
the lateral femoral condyle, a load-bearing region where
�22% of arthroscopically diagnosed chondral defects
occur (28,29). The biomechanical factors associated with
early degeneration in such load-bearing regions may
contribute to the progressive degeneration of articular
cartilage. Although the samples used had been previously
frozen, a single freeze–thaw cycle does not result in
marked changes in compressive properties of normal
(30) or degenerated (31) articular cartilage or its structure
(32), and is thus unlikely to have marked effects on
shear properties. Although the distal femoral condyle
normally apposes the tibial plateau, cartilage from the
femoral condyle was apposed against itself to create a

2072 WONG ET AL
simplified symmetric loading situation. Cartilage from
other sites could be examined in future studies.
The testing protocol used in this study provides a
mechanical environment mimicking the compression
and sliding of articular cartilage during normal joint
loading. A knee undergoes a wide range of dynamic
compression (up to 5–20%) (1,2) and sliding (up to �50
mm) during normal activities (estimated from refs. 23
and 24). The present analysis addresses certain parts of
the gait cycle (e.g., contralateral toe-off and heel rise
[23]) in which compressive loading is high and sliding
velocity is low, during which time interaction of apposing
tissue surfaces is likely to be initiated. Since samples
were allowed to stress-relax for 1 hour, the pattern of
cartilage deformation and strain is likely to be representative
of that occurring after prolonged cyclic loading
and sliding, rather than that which occurs at the onset of
cyclic loading. Cartilage gradually depressurizes and
reaches an averaged steady-state compression under
prolonged cyclic loading. During this time, interstitial
fluid pressure diminishes (33), and boundary lubrication
becomes increasingly important (7). The ratedependence
of shear deformation was not assessed;
however, shear deformation may not change markedly
with rate of lateral displacement since kinetic friction
remains fairly constant with sliding velocity (7). Additional
studies might elucidate the time course of cartilage
shear after the onset of loading, as well as effects of
sliding velocity on shear deformation.
Although edge effects may occur in this shear
testing protocol, such effects are likely minimal in the
central area of tissue that was analyzed. Boundaries of
the analyzed region were �2 mm away from both the
leading and the trailing edges of the samples. Recent
studies have shown that intratissue deformation (Gratz
KR, et al: unpublished observations) and stiffness (34)
are affected only �1–2 mm from vertical boundaries of
cartilage. Thus, the results are likely to be representative
of the major areas of cartilage contact.
The reduction in E xz with SF as lubricant is
consistent with predictions derived from a variety of past
studies on cartilage friction. The friction coefficient
decreases with the use of SF as lubricant compared with
saline, both in cartilage-on-cartilage in the boundary
mode (7,35) and in whole joint (36–38) friction tests.
Assuming cartilage material properties (i.e., compressive
and shear modulus) are maintained with the use of
SF and PBS, the friction-reducing property of SF would
be predicted to result in a reduction of tissue E xz.
The overall E xz values obtained in this study are
consistent with values estimated during physiologic joint
articulation based on previously reported material properties
of cartilage, as follows. To provide a first-order
estimate of tissue properties, cartilage can be modeled
as a linear, homogeneous, isotropic, and elastic tissue.
With such assumptions and under small strain conditions,
the overall stiffness of cartilage in shear (G) can be
related to the shear stress (� xz) and the resulting overall
E xz (27) as follows: G � � xz/2E xz (equation 1). In
addition, � xz acting on cartilage can be related to the
friction coefficient (�) and normal contact stress (� n)as
follows: � xz � �� n (equation 2). Substituting equation 2
into equation 1 and rearranging terms, cartilage E xz can
be expressed as E xz � �� n/G (equation 3).
Using reported values of � (�0.01) (39) and � n
(�2 Mpa) (40) and the overall G values of �0.2–0.4
MPa found in this study, the estimated overall E xz is
0.02–0.05. The estimate of E xz is consistent with the
range of overall E xz determined in this study (Figure
5B). This suggests that an overall E xz ranging from 0.01
to 0.1 may be suitable for biomimetic in vitro simulation
of physiologic shear loading, for example during mechanical
evaluation and mechanical stimulation for tissue
engineering of cartilage.
The increased E xz with degeneration, particularly
near the surface with SF as lubricant (Figure 5A),
appears to be due to both increased friction between
sliding surfaces and a reduction in tissue shear modulus.
Roughened surfaces have local asperities that can cause
increased interaction and adherence between tissue surfaces,
enhancing friction during sliding. Since boundary
lubricants modulate friction, higher E xz in degenerated
cartilage when tested in PBS (Figure 5A) indicates that
friction between degenerated surfaces is higher than that
between normal surfaces. Additionally, with degeneration,
cartilage mechanical properties, such as G, become
impaired (12). Diminished G would result in increased
cartilage E xz at the same magnitude of � xz (equation 3),
even if friction coefficient were similar. Since surface E xz
increased with degeneration with the use of SF as
lubricant, and G near the surface tended to diminish
with degeneration, the elevated E xz at the surface in
mildly degenerated tissue is likely a result of both
increased � and reduced G (equation 3 and Figure 5A).
Depth variations in E xz and G in the cartilage
samples used in the present study provide additional
information on the depth-varying biomechanical properties
of articular cartilage. Compressive strain is depthvarying
in both statically (4) and dynamically (3) compressed
cartilage, decreasing monotonically with depth
from the articular surface. E xz observed in this study was
similarly depth-varying, being highest near the surface

LUBRICATION AND DEGENERATION EFFECTS ON CARTILAGE SHEAR DURING ARTICULATION 2073
and lowest near the tidemark (Figures 4A and B).
Compressive modulus, deduced from the overall compressive
stress and local strain, was reflective of the
depth-varying strain magnitudes, with cartilage increasing
in stiffness with increasing depth (4). Similarly, G
was lowest near the articular surface and increased
monotonically to a maximum (20%) in the deepest
region (Figure 4C). While G near the surface only
tended to decrease with degeneration, the lack of statistical
significance was likely due to the calculation from 2
measurements, shear stress and strain (each having
variability), as well as donor variability.
The overall unconfined compressive modulus at
equilibrium found in this study (E � 0.79 MPa) is
consistent with previously reported values in human
cartilage (0.58 MPa) (41). The overall shear properties
of human cartilage have yet to be reported; however,
overall G can be estimated from Poisson’s ratio (�) and
the aggregate modulus (H A) demonstrated in indentation
tests, using the relationship
G � H A�1 � ���1 � 2��
2�1 � ���1 � ��
(27,42). The overall G found in this study (0.32 MPa) is
consistent with that estimated from indentation tests
(0.2–0.4 MPa) (43). Thus, for cartilage in compression,
the deformation and mechanical properties we observed
are consistent with findings of previous studies, and for
cartilage in shear, the newly described depth-varying
strain and shear properties are within values predicted
for full-thickness human cartilage.
With cartilage degeneration, tissue structure and
low cellularity may affect the analysis and interpretation
of deformation and strain. Degenerated cartilage contains
clefts and areas of erosion (20), both of which
result in material discontinuities within cartilage. Thus,
continuum assumptions are not strictly valid. Also, compatibility
conditions (27) are not maintained when fibrillated
tissues overlap during deformation. Nevertheless,
the present samples were only mildly degenerated and
relatively intact except at the surface, and, whereas there
were few visible cells at the surface of the degenerated
samples, cells near the surface (3–5% depth) could be
tracked. From a linear extrapolation, this may have
resulted in a slight (�15%) underestimation of the
absolute magnitude of superficial shear strain.
The present results suggest that changes in E xz
magnitudes and shear behavior may contribute to cartilage
degeneration and pathogenesis. While samples
were tested with a common overall compressive strain in
this study, marked differences in E xz between groups
occurred even with this conservative testing protocol.
Under similar loads instead of overall strain, softer
tissues (i.e., degenerated cartilage) would exhibit larger
compressive and shear strain, excessive levels of which
can contribute to cartilage degeneration. Excessive magnitudes
of compressive strain result in mechanical injury
to cells (44,45) and matrix (45,46), leading to reduced
cartilage remodeling, maintenance, and repair. Likewise,
high E xz that results from degenerated matrix,
along with deficient lubrication, may lead to additional
degeneration. Cell death and matrix damage may spread
with continued exposure to high E xz, diminishing local
mechanical properties of cartilage in both compression
and shear. Cartilage E xz may then further increase and
further the changes in tissue structure, resulting in a
self-propagating cycle of degeneration. Such mechanical
effects may also induce changes in surrounding joint
tissues and the biochemical environment, which could
supplement cartilage deterioration.
ACKNOWLEDGMENTS
We thank the many residents and staff at Dr. Lotz’s
Laboratory at the Scripps Research Institute for harvesting
and providing the human tissue used in this study, and Barbara
Schumacher for guidance on histopathologic processing.
AUTHOR CONTRIBUTIONS
Dr. Sah had full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the data
analysis.
Study design. Wong, Bae, Sah.
Acquisition of data. Wong, Chun, Lotz.
Analysis and interpretation of data. Wong, Bae, Gratz, Sah.
Manuscript preparation. Wong, Bae, Sah.
Statistical analysis. Wong, Bae, Sah.
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Effect of a Focal Articular Defect on Cartilage Deformation during
Patello-Femoral Articulation
Benjamin L. Wong, Robert L. Sah
Department of Bioengineering, University of California—San Diego, 9500 Gilman Drive, La Jolla, California
Received 3 August 2009; accepted 22 April 2009
Published online 2 July 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jor.21187
ABSTRACT: The objective of this study was to determine cartilage strains near, and in apposition to, a focal defect during patello-femoral
articulation. Bovine osteochondral blocks from the trochlea (TRO) and patella (PAT) were apposed, compressed 12%, and subjected to
sliding under video microscopy. Samples, lubricated with synovial fluid, were tested intact and then with a full-thickness defect in PAT
cartilage. Shear (Exz), axial (Ezz), and lateral (Exx) strains were determined locally for TRO and PAT cartilage. For articulation with a
focal defect, the strain amplitudes of PAT cartilage near the surface were ∼2–8× lower in Exz and ∼1.4× higher in −Ezz than intact PAT
cartilage. At 20% depth, Exz and Exx for PAT cartilage with a focal defect were ∼2× and ∼10–25× higher than intact PAT, respectively.
For TRO articulating against a focal defect, Exz and −Ezz near the surface and at 20% depth were ∼2–4× lower than that for articulation
against intact cartilage. The results elucidate dramatic region-specific changes in strain due to lateral motion. In these regions, such
altered cartilage mechanics during knee movement may cause focal defects to extend by induction of damaging levels of strain to bordering
regions of cartilage. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop. Res. 28: 1554–1561, 2010
Keywords: focal defect; articulation; biomechanics; deformation; cartilage strains
Focal articular defects are prevalent in symptomatic
knees and are associated with progressive cartilage
degeneration. In patients evaluated arthroscopically,
focal defects were found in 20–60% of all symptomatic
knees, occurring most frequently in the medial condyle
and patella, both of which are load-bearing regions (Fig.
1). 1–4 Such, focal defects typically ranged from 0.5 to
4cm 2 in area with an average area of 2.1 cm 2 , and
extended beyond half the cartilage thickness in depth
in 50% of all visualized articular defects. 1 With continued
joint loading and time, untreated defects enlarge, 5
are associated with cartilage volume loss, 6 and exhibit
histopathological signs of cartilage degeneration adjacent
to the focal defect. 7,8 While such findings suggest
that the presence of a focal defect predisposes joints
to secondary osteoarthritis, the mechanism by which it
causes cartilage to degenerate within the proximity of a
focal defect remains to be elucidated.
The effect of a focal defect on cartilage deformation
has been examined during axially directed loading.
Under axial compression alone, contact stress and
stress gradients are elevated in areas of cartilage near
the edges of a focal defect. 9,10 As a result, macroscopic
tissue deformation 11 and local strains 12 are
increased markedly in these regions. Elevated strains
may reach levels that induce cell death 13 and matrix
damage, 14 and thus, the elevated strains resulting from
a focal defect may become injurious to cartilage and
induce degeneration. Such tissue deformation may be
altered by or accentuated by the addition of lateral
motion superimposed on compression, as both occur
Additional Supporting Information may be found in the online
version of this article.
Correspondence to: Robert L. Sah (T: 858-534-0821;
F: 858-822-1614.; E-mail: rsah@ucsd.edu)
© 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
1554 JOURNAL OF ORTHOPAEDIC RESEARCH DECEMBER 2010
in load-bearing regions of cartilage during joint movement.
During knee movement, articular surfaces contact,
compress, and articulate against each other. Within the
patellofemoral groove of the knee, patellar cartilage
contacts and slides against trochlear cartilage during
normal joint movement and loading (Fig. 2A). Under
applied compressive loads of ∼1.5× the body weight,
patellofemoral cartilage compresses ∼10% of its overall
thickness in vitro following 14 min of static loading, 15
and following knee bending, patellar cartilage alone
compresses about ∼5–10% overall in vivo. 16 Collectively,
such results provide physiologic mechanical parameters
for the in vitro testing of patello-femoral articulation.
Recently, local and overall deformation of cartilage
during compression and cartilage articulation 17 were
determined using video microscopy 18 and image correlation
to track the displacement of fiducial markers. 19,20
Such a test configuration can be applied to study contact
of patellar and trochlear cartilage surfaces, 21,22 to
examine the effects of a focal articular defect on the
deformation of cartilage near, and in apposition to, the
proximal defect edge that experiences oncoming forward
motion of the apposing surface during compression and
lateral displacement (Fig. 2). Effects of a focal defect on
cartilage deformation may be distinctly and markedly
different during compression than during shear.
Therefore, the hypothesis of this study was that during
patellofemoral cartilage articulation, the cartilage
deformation of the patella and trochlea are markedly
altered with the presence of a focal articular defect.
The specific objective of this study was to determine the
effects of a focal articular defect, created in the patellar
tissue, on the local and overall strains of the patellar
and trochlear cartilage during compression and sliding
motion.

Figure 1. Anatomical distribution of focal articular defects averaged
from four previous arthroscopy studies on the prevalence of
cartilage defects in symptomatic knees. 1–4
Figure 2. Schematic of (A) knee joint movements at multiple
scales, (B) experimental setup and loading protocol for micro-shear
testing, (C) and locations of sub-regions (EDGE, MID, FAR) used
for statistical analysis of strains in patella and trochlear cartilage.
EFFECT OF A FOCAL DEFECT ON CARTILAGE DEFORMATION 1555
MATERIALS AND METHODS
Sample Isolation and Preparation
Osteochondral cores with macroscopically normal cartilage
were harvested from the trochlea (TRO) and patella (PAT)
of four adult bovine animals (1–2 years). Using a low speed
drill press with custom stainless steel coring bits, a 10 mm
diameter osteochondral core was isolated from both the TRO
and PAT of each joint in a manner similar to that described
previously. 23 The TRO and PAT cores were then trimmed to
each yield one approximately rectangular block for biomechanical
testing. 17 Each rectangular block had a cartilage surface
area of ∼3 × 10 mm 2 and a total thickness of ∼1 cm (Fig. 2A).
Each sample consisted of one TRO and one PAT block from the
same knee, and was stored in phosphate buffered saline (PBS)
containing proteinase inhibitors (PI) until testing.
Prior to mechanical testing, samples were stained for
∼2–4 h at 4 ◦ C in PBS + PI and propidium iodide (20 �g/mL) to
fluorescently highlight cell nuclei. Blocks were then bathed in
normal bovine synovial fluid (SF) containing PI and propidium
iodide (20 �g/mL) at 4 ◦ C for 12–16 h to lubricate surfaces. The
SF was pooled from adult bovine knees, previously characterized
for boundary lubrication properties and lubricant levels
and stored at −80 ◦ C, and characterized previously for boundary
lubrication properties and lubricant molecules levels. 23
Experimental Design
To characterize the effect of a focal defect on cartilage deformation
during articulation, samples were mechanically tested,
first intact and then with a focal defect. In between tests, samples
were rinsed, allowed to reswell, and incubated for ∼2–4 h
in PBS + PI and then in SF + PI for an additional 12–16 h at
4 ◦ C. Following the mechanical testing of intact samples and
reincubation, a full thickness (∼2 mm in depth), 3 mm wide
focal articular defect was created in the center of the PAT cartilage
(Fig. 2A) as described previously. 12 The width of the focal
defect was chosen so to be wide relative to the articulation distance
(described below) in order to focus on the initial stages
of articulation.
Micro-Scale Shear Testing
Samples were shear tested under video microscopy essentially
as described previously. 17 Briefly, each TRO and PAT pair
was secured in a custom bi-axial loading chamber mounted
onto an epi-fluorescence microscope for digital video imaging
(Fig. 2B). 18 The chamber secured the PAT block at the bone
and allowed in-plane movement of the apposing mobile TRO
block with orthogonally positioned plungers. 17 Subsequently,
an axial displacement was applied (∼40 �m/s) to induce 12%
compression (1 − �z, where �z is the stretch ratio 24 ) of the overall
cartilage thickness (Fig. 2B). Samples were then allowed
to stress relax for 1 h, determined to be sufficient to reach
an approximate equilibrium stress for the current sample
geometries. 17 Cartilage deformation was then captured during
lateral motion separately in the TRO and PAT cartilage
following axial compression. Three sets of applied lateral displacements
(�x), each consisting of +1 mm and then −1mm
(returning to initial position) were applied at 100 �m/s to the
bone portion of the TRO block (Fig. 2B). The first set, was for
preconditioning, 23 while the second and third set were recorded
for the PAT and TRO blocks for analysis, respectively. Deformation
during patello-femoral cartilage articulation was captured
with sequential fluorescence images taken at ∼25 �m increments
of lateral displacement.
JOURNAL OF ORTHOPAEDIC RESEARCH DECEMBER 2010

1556 WONG AND SAH
Data Collection and Calculations
Acquired images were analyzed as described previously 17,20
to determine the depth-varying and overall deformation
and strain in cartilage. Evenly distributed cell nuclei
(∼250 cells/mm 2 ) were tracked during lateral motion to determine
the displacements of uniformly spaced (10 pixel) mesh
points in local regions. Subsequently, Lagrangian shear (Exz),
axial (Ezz), and lateral (Exx) strains were determined relative
to the unloaded state, 24 when articular surfaces were sliding
(�x = 0.8 mm) and strains had become steady. Local strains
were determined by averaging both depth-wise and at various
lateral distances from the defect edge. First, sample thickness
was normalized and divided into 8 intervals, with 4 intervals
being 0.083 times the normalized thickness near the articular
surface (i.e., 0–0.333) and 0.167 times for the remaining tissue
depth (i.e., 0.333–1). To reduce noise and consolidate data, PAT
cartilage strains near the proximal defect edge, which experiences
forward lateral motion, were averaged depth-wise for
lateral regions (∼0.2 mm × full cartilage thickness) at (EDGE),
∼0.4 mm (MID) and ∼0.8 mm (FAR) away from the defect edge
to yield a depth-profile at varying lateral distances (Fig. 2C).
For TRO cartilage in direct apposition to the focal defect prior
to lateral motion, strains following lateral articulation were
averaged depth-wise in lateral regions (∼0.15 mm × full cartilage
thickness) at (EDGE), ∼0.3 mm (MID), and ∼0.5 mm
(FAR) away from the defect edge. For intact tissue, strains
in corresponding lateral regions were determined similarly.
Overall strain values were determined as the mean of all local
values.
Statistical Analysis
Data are reported as mean ± standard error of the mean
(SEM). Repeated measures ANOVA was used to determine the
effects of a focal defect (intact vs. defect), tissue depth, and lateral
location from the defect edge (EDGE, MID, FAR) on local
and overall strains. Differences between defect and intact samples
at the various lateral locations were assessed by planned
pair-wise comparisons.
Figure 3. Representative micrographs of patellar cartilage as (A,D,G) intact or (B,E,H) with a focal defect with superimposed colormaps
of (A,B) shear (Exz), (D,E) axial (−Ezz), and (G,H) lateral (Exx) strain maps when articulating against trochlear samples after articular
surfaces have slid. Strain map boundaries encompass the corresponding deformed states. Local (C) shear (Exz), (F) axial (−Ezz), and (I)
lateral (Exx) strain averaged depth-wise versus normalized tissue depth for patella cartilage as intact or with a focal defect. For samples
with a focal defect, strains were also determined as a function of lateral distance from the defect edge (EDGE, MID, FAR).
JOURNAL OF ORTHOPAEDIC RESEARCH DECEMBER 2010

RESULTS
Qualitatively, the deformations of intact PAT and TRO
cartilage were similar, being depth-varying during axial
compression as well as during lateral motion. Cartilage
thickness was similar between intact samples, being
1.97 ± 0.13 mm and 1.93 ± 0.14 mm for PAT and TRO
tissue, respectively. Under compression, axial deformation
of intact PAT and TRO cartilage were similarly
depth-varying, being highest near the surface and lowest
near the tidemark. Also during compression, shear
and lateral deformation were low (

1558 WONG AND SAH
Figure 5. Representative micrographs of trochlear cartilage with superimposed colormaps of (A,B) shear (Exz), (D,E) axial (−Ezz), and
(G,H) lateral (Exx) strain when in apposition with patellar cartilage as (A,D,G) intact or (B,E,H) with a focal defect during lateral motion.
Dashed lines (– –) encompass the analyzed regions prior to lateral motion, while boundaries of strain maps encompass the corresponding
deformed states. Local (C) shear (Exz), (F) axial (−Ezz), and (I) lateral (Exx) strain averaged depth-wise versus normalized tissue depth
for trochlear cartilage, intact or with a focal defect. For samples apposing a focal defect, strains were also determined as a function of
lateral distance from the defect edge (EDGE, MID, FAR).
a defect decreased with increasing lateral distance from
the defect edge (p < 0.01). Thus, when TRO cartilage filling
the focal defect slides over the proximal defect edge,
PAT cartilage near a focal defect compresses more than
intact cartilage near the surface and overall.
Lateral Strain (Exx)
With articulation, the resultant Exx for intact cartilage
did not vary significantly with tissue depth (p = 0.2) and
lateral location (p = 1.0) (Fig. 3G), while for cartilage
with a defect, Exx varied with tissue depth (p < 0.001)
and lateral region (p < 0.01) (Fig. 3H). For all lateral
regions, Exx remained negligible (≤0.01) for intact cartilage
throughout tissue depth and peaked at ∼20% depth
for defect samples (Fig. 3I). Near the articular surface,
Exx for cartilage with a defect were statistically indifferent
(p = 0.4) from that for intact cartilage and did not
JOURNAL OF ORTHOPAEDIC RESEARCH DECEMBER 2010
significantly (p = 0.6) vary with lateral distance (Fig.
4G). At 20% tissue depth (Fig. 4H) and overall (Fig.
4I), cartilage Exx peaked at a value of ∼0.08 and ∼0.03,
respectively, in the MID region for cartilage with a defect
(p < 0.01) and were significantly higher than Exx for
intact cartilage (p < 0.01). Thus, PAT cartilage expands
laterally at 20% tissue depth as it becomes further compressed
when TRO cartilage filling the focal defect slides
over the defect edge.
Trochlear Cartilage Deformation
During patello-femoral articulation, the depth-variation
in strains of TRO cartilage in articulation with an intact
and defect-containing PAT surface were similar to that
of PAT cartilage (Fig. 5), and the effect of a focal defect
on TRO cartilage strains were also marked (Fig. 6).
For TRO cartilage in articulation with an intact PAT

Figure 6. Effect of a focal defect (intact (I) vs. defect (D)) on (A–C)
shear, (D–F) axial, and (G–I) lateral strain (A,D,G) near the articular
surface, (B,E,H) at 20% tissue depth, and (C,F,I) overall of
trochlear cartilage during articulation.
surface, Exz and −Ezz were highest near the surface and
decreased with increasing depth (p < 0.001), while Exx
remained negligible throughout tissue depth (p = 0.6).
All strains did not vary with lateral region for TRO
articulation with intact PAT cartilage (p = 0.15–0.6). For
TRO cartilage in articulation with a focal defect, Exz
and −Ezz were ∼2–3× (p < 0.05, Fig. 6A) and ∼2–4×
(p < 0.01, Fig. 6D), respectively, less near the surface
than when in articulation with an intact surface. Furthermore,
TRO cartilage compressed laterally in the
EDGE region near the surface, and Exx near the surface
markedly increased with lateral distance (p < 0.05),
transitioning into lateral tension in the MID and FAR
regions (Fig. 6G). The effects of tissue depth, lateral
region, and a focal defect on TRO strains during lateral
articulation are described in further detail in the
supplementary data.
DISCUSSION
This study elucidated the deformation of cartilage
within the proximity of, and directly in apposition to,
EFFECT OF A FOCAL DEFECT ON CARTILAGE DEFORMATION 1559
a focal articular defect during patello-femoral cartilage
articulation. As the TRO surface displaced laterally, the
tissue partially filling the focal defect pushed and then
plowed over the proximal defect edge. As a result, PAT
cartilage proximal to the defect sheared markedly less
(∼70–700%) near the surface and more (∼50–60%) at
20% tissue depth than intact cartilage during lateral
motion (Fig. 7). PAT cartilage near the focal defect also
compressed more (30–40%) than intact cartilage, and
expanded laterally ∼10–25× more at 20% tissue depth
than intact cartilage as TRO cartilage translated laterally
over the proximal defect edge. For regions directly in
apposition to the focal defect, TRO cartilage sheared and
compressed less (∼50–70%) than when it slid over intact
cartilage. As the TRO surface plowed over the proximal
defect edge, TRO cartilage near the surface also compressed
laterally at the EDGE region, and expanded
laterally at MID and FAR regions. Collectively, the current
results indicate that with articulation, the tissue
deformation of both the cartilage adjacent to, and in
apposition to, a focal defect are altered drastically by
the presence of a focal defect, extending the findings of
strain analysis of cartilage when compressed. 12
To replicate the physiologic articulation and lubrication
of cartilage surfaces, osteochondral samples were
isolated from the trochlear and patella and tested in
apposition with normal bovine synovial fluid. While
efforts were not taken to ensure trochlear and patellar
samples were in exact apposition and registration
in the native anatomical joint, patellar cartilage translates
a distance of ∼2.7 cm over the trochlear surface
(estimated from Refs. 25,26 ). Since samples were isolated
from matching anatomical aspects (i.e., lateral or
medial), samples likely apposed and slid against one
another during anatomic articulation. Since the medial
femoral condyle is the site of greatest incidence of focal
lesions, 1–4 condylar cartilage are of interest. However, it
has a greater curvature in the saggital plane and articulates
against both tibial and meniscal cartilage during
knee movement. Thus, effects of a focal defect on condylar
cartilage are likely to be somewhat more complex and
remain to be investigated. A relative sliding distance of
1 mm was sufficient to result in deformations reaching
a steady-state for both intact and defect samples (data
not shown). Thus, deformations described in the present
study would likely be representative of greater, more
physiologic, sliding distances.
The defect geometry for the present samples was
a full thickness slot with sharp edges in a rectangular
osteochondral block and is a simple model of focal
articular defects. Such a configuration would be most
representative of a partially apposed and loaded defect,
since completely covered defects would have a significant
hoop stress around the defect rim that would help
resistance deformation during articulation. Additional
analyses to address complex three-dimensional issues
would be useful in future studies. Furthermore, defect
edges that are rounded, smoothed, or blunted may also
occur, which may minimize tissue strains near focal
JOURNAL OF ORTHOPAEDIC RESEARCH DECEMBER 2010

1560 WONG AND SAH
Figure 7. (A) Schematic depicting the effect of a focal defect on tissue deformation of trochlear and patellar cartilage when unloaded,
compressed, and compressed and sheared in apposition. (B) Table of relative changes in shear (Exz), axial (−Ezz), and lateral (Exx)
strains compared to normal intact cartilage (i.e., without a focal defect) for both trochlear and patellar cartilage when they are unloaded,
compressed, and compressed and sheared in apposition.
defects. While the present study provides analysis for
a particular set of defect geometries, others remain to
be investigated.
While patellar cartilage was analyzed up to the articular
surface, the region very close to the trochlear
surface (∼10% of tissue depth), which partially filled the
defect, was not analyzed because during lateral motion,
tissue compression was so extensive in that region that
cell nuclei coalesced and could not be discriminated and
tracked. However, regions directly in apposition of the
defect edge (EDGE) prior to lateral motion were tracked
appropriately near the surface. Thus, strains in other
lateral regions (MID, FAR) of the trochlear cartilage may
be somewhat (∼10–15%) underestimated and may be
more similar to the values of the EDGE lateral region.
The dramatic elevation in cartilage strains near a
focal defect during lateral articulation may be related
and possibly contribute to, the progressive tissue degeneration
associated with focal defects. With joint loading
and time, increased fibrillation and decreased matrix
staining were noted in regions adjacent to a focal defect
in animal models. 7,8 Also, untreated defects in human
knee joints have been shown to enlarge 5 and be associated
with cartilage volume loss. 6 Markedly elevated
strains likely make cartilage susceptible to damage in
these regions, via cell death 13 and matrix damage, 14
which can be induced by high magnitudes of compression.
With repeated loading during joint movement, the
increased Exz and Exx at 20% tissue depth, as well as
the elevated −Ezz near the surface, may all contribute
to inducing the indicators of tissue degeneration characterized
previously near the focal defect edge. Thus, focal
JOURNAL OF ORTHOPAEDIC RESEARCH DECEMBER 2010
defects may enlarge due to articulation-induced strain,
and damage the bordering regions of cartilage.
For cartilage in direct apposition to focal defects, the
reduction in localized strains during lateral articulation
may be related to the low incidences of two focal defects
being in direct apposition (i.e., “kissing lesions”). Focal
defects found on both apposing cartilage surfaces were
found in only ∼2% of the symptomatic knees arthroscopically
diagnosed with focal defects. 3 The low frequency
of kissing lesions may be attributed the reduction in
Exz and −Ezz of cartilage when in articulation with
a focal defect. Since strain magnitudes are lowered, a
chondral defect may be unlikely to develop from a preexisting
focal defect on the opposing surface. Instead,
kissing lesions may form with the defects being initiated
concurrently at the time of injury or with one lesion
enlarging big enough to become full-thickness in depth
and cause the apposing chondral surface to be in articulation
against the subchondral bone, inducing abrasive
wear.
The present study suggests that focal articular
defects drastically alter cartilage deformation of both
apposing cartilage surfaces not only during axial loading,
but also distinctly during lateral articulation. Focal
defects, of which a majority (∼61%) has been associated
with acute injury or trauma, 1 markedly alter the
mechanical environment of cartilage, and the resulting
abnormal strains may be injurious to cells and
matrix. Mechanically induced cell death and tissue loss
reduce cell population and likely compromise the overall
biosynthetic response of the tissue. 27 The metabolic
activities of the remaining cells that may continue

to experience injurious levels of strain, are markedly
altered. 13,14 As a result, tissue repair and remodeling
responses are likely compromised, facilitating changes
in cartilage structure by degeneration and wear. Thus,
rehabilitation protocols, such as a period of non-weight
bearing following acute injury, may be beneficial for
allowing repair as well as limiting damage to the
remaining native cartilage following surgical procedures
such as debridement. Thus with normal loading,
the changes in cartilage deformation associated with
focal effects during both axial loading and lateral articulation
may contribute to the enlargement of focal defects
and predispose joints to secondary osteoarthritis.
ACKNOWLEDGMENTS
This work was supported by NIH and the Howard Hughes
Medical Institute through the Professors Program to UCSD (to
R.L.S.). We thank Chris Kim and Alexander Cigan for assistance
with the sample preparations.
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doi:10.2106/JBJS.K.00046
Effect of Tibial Plateau Fracture on Lubrication
Function and Composition of Synovial Fluid
Brooke L. Ballard, MD*, Jennifer M. Antonacci, PhD*, Michele M. Temple-Wong, PhD, Alexander Y.
Hui, BS, Barbara L. Schumacher, BS, William D. Bugbee, MD, Alexandra K. Schwartz, MD, Paul J.
Girard, MD, and Robert L. Sah, MD, ScD
Investigation performed at the Department of Orthopaedic Surgery, University of California, San Diego, San
Diego, and Department of Bioengineering, University of California, San Diego, La Jolla, California

Effect of Tibial Plateau Fracture on Page 3 of 25
Lubrication Function and Composition of Synovial Fluid 8/22/2011
Effect of Tibial Plateau Fracture on Page 2 of 25
Lubrication Function and Composition of Synovial Fluid 8/22/2011
regression analysis indicated that kinetic friction coefficient increased as hyaluronan
1
Abstract
1
concentration decreased.
2
Background: Intra-articular fractures may hasten post-traumatic arthritis in patients who are
2
Conclusions: Joints afflicted with a tibial plateau fracture have synovial fluid with decreased
3
typically too active and young for joint replacement. Current orthopaedic treatment principles,
3
lubrication properties in association with a decreased concentration of hyaluronan.
4
including recreating anatomic alignment and establishing articular congruity, have not eliminated
4
Clinical Relevance: Tibial plateau fractures result in a post-traumatic deficiency in synovial fluid
5
post-traumatic arthritis. Additional biomechanical and biological factors may contribute to the
5
lubrication function.
6
development of arthritis. The objective of the present study was to evaluate human synovial fluid
6
7
following tibial plateau fractures for friction-lowering function and the concentrations of putative
7
lubricant molecules.
8
Methods: Synovial fluid specimens were obtained from the knees of eight patients (25-57 years
9
old) with a tibial plateau fracture, with five specimens from the injured knee as injury
10
synovial fluid and six specimens from contralateral knees as control synovial fluid. Each
11
specimen was centrifuged to obtain a fluid sample, separated from a cell pellet, for further
12
analysis. For each fluid sample, the start-up (static) and steady-state (kinetic) friction coefficients
13
in the boundary mode of lubrication were determined from a cartilage-on-cartilage
14
biomechanical test of friction. Also, concentrations of the putative lubricants, hyaluronan and
15
proteoglycan-4, as well as total protein, were determined for fluid samples.
16
Results: The injury group of experimental samples was from patients 45±13 years old
17
(mean±SD), after a post-injury period of 11±9 days. Start-up and kinetic friction coefficient
18
demonstrated similar trends and dependencies. The kinetic friction coefficients for human
19
plateau fracture synovial fluid were ~100% higher than that of control human synovial fluid.
20
Hyaluronan concentrations were 9-fold lower for plateau fracture synovial fluid compared with
21
the control synovial fluid, whereas proteoglycan-4 concentrations were >2-fold higher in plateau
22
fracture synovial fluid compared with the control synovial fluid. Univariate and multivariate
23

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cellular components from damaged tissues and bone marrow infiltrate the joint space 13,19-22 .
1
Introduction
1
Such alteration of synovial fluid may disrupt its lubrication functions.
2
Traumatic intra-articular fractures, such as those of the tibial plateau, are at risk of joint
2
Alteration in the lubricating function and lubricant composition of synovial fluid appears to
3
degeneration and post-traumatic arthritis even when treated according to traditional orthopaedic
3
be involved in cartilage deterioration after anterior cruciate ligament (ACL) injury, as well as
4
principles to restore articular congruency and anatomic alignment 1-7 . The consequences of poor
4
other injuries of the knee joint. After ACL injury of human knees, the level of proteoglycan-4 in
5
results can be life-changing–painful weight-bearing, restricted activity and lost time in the work
5
synovial fluid was reduced, while levels of degradative enzymes, cartilage matrix degradation
6
force 1,8-10 . The costs of post-traumatic arthritis are a component of the estimated >$100 billion
6
products, and inflammatory markers were increased for up to 6-18 months after injury 15,23 .
7
annual burden of osteoarthritis on the U.S. economy, with 9.8% of knee osteoarthritis estimated
7
Deficient lubrication after an injury has similarly been detected in the synovial fluid from acutely
8
to be of post-trauma etiology; furthermore, patients with post-traumatic arthritis and its chronic
8
injured equine joints, in association with a decreased concentration of hyaluronan 24 . In guinea
9
consequences tend to be younger with an additional impact on employment 9 . Compared to
9
pig 25 and rat 26,27 models of knee joint injury, synovial fluid lubrication function and lubricant
10
patients without post-traumatic arthritis, patients with post-traumatic arthritis have worse clinical
10
levels are also diminished. These studies suggest that human knee trauma, and specifically intra-
11
outcomes after arthrodesis or arthroplasty 11,12 . Post-traumatic arthritis and its consequences have
11
articular tibial plateau fracture, may lead to a deficiency in synovial fluid lubrication.
12
not been eliminated by employing traditional orthopedic principles, suggesting a possible role for
12
The hypothesis tested in the present study was that tibial plateau fractures impair the friction-
13
additional biological and biomechanical factors.
13
lowering lubrication function of human synovial fluid in association with changes in the
14
The pathogenesis of post-traumatic arthritis is complex and multifactorial. Recent studies
14
concentrations of proteoglycan-4 and hyaluronan lubricant molecules. The objectives of this
15
have focused on articular chondrocyte death and cartilage damage due to direct trauma, enzyme-
15
study were to compare the trauma synovial fluid from joints afflicted with acute tibial plateau
16
mediated cartilage degradation, and the role of reactive oxygen species 13-16 . Deficient lubrication
16
fractures with normal synovial fluid in terms of 1) friction-lowering boundary lubrication
17
may also contribute to cartilage deterioration after trauma. Lubrication typically allows articular
17
function and 2) biochemical composition, including hyaluronan and proteoglycan-4
18
cartilage to bear load and slide with low friction and low wear 17 , and is mediated by high levels
18
concentrations. In addition, the possible biomechanical basis for impaired lubricant function was
19
of proteoglycan-4 and hyaluronan in synovial fluid 18 . Synovial fluid lubricant molecules are
19
assessed by correlating friction coefficient and lubricant concentration.
20
secreted by chondrocytes and synoviocytes lining the joint, and are concentrated through
20
21
selective retention by synovium. However, after an intra-articular fracture, soft tissues that
21
Materials and Methods
22
normally produce and retain synovial fluid lubricants are damaged, and in addition, blood and
22

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but Ctrl-hSF were not of sufficient volume. Thus, three other Ctrl-hSF samples were used from
1
Materials. Materials for lubrication testing were obtained as previously described 28 . The
1
other patients. Radiographs of the contralateral knee were evaluated by radiologists and
2
antibody to proteoglycan-4 was that to Lubricin from AbCam (Cambridge, MA); Streptomyces
2
orthopaedists and confirmed to not have an acute injury. To obtain fluid, following sterilization
3
hyaluronidase was from Seikagaku (Tokyo, Japan); SeaKem gold agaraose (Lonza) was from
3
of skin overlying each joint, a standard 18 gauge hollow bore spinal needle from Becton-
4
Fisher Scientific (Pittsburg, PA) and SDS-horizontal agarose gel electrophoresis and Western
4
Dickinson attached to a 60cc syringe barrel from Becton-Dickinson (Laguna Hills, CA) was
5
blot materials were from Life Technologies (Carlsbad, CA). EDTA-treated adult human blood
5
introduced into the joint space and SF was aspirated. The site of needle introduction into the
6
was purchased from Golden West Biologicals (Temecula, CA). EDTA-treated bovine blood was
6
knee joint was at the level of the joint line, 1 cm medial or lateral to the patellar ligament on the
7
from Animal Technologies (Tyler, TX).
7
anterior aspect of the knee 30 .
8
Patient Samples and Fracture Classification. Samples of human synovial fluid (hSF) were
8
Experimental Design. Gross Analysis of hSF Samples. Samples were initially studied by
9
aspirated from consented patients at a level one trauma center under the auspices of an IRB-
9
gross examination for color and clarity. Samples were noted to be straw-colored or bloody.
10
approved research plan. Patients 21 years and older, scheduled for surgery after sustaining a
10
Clarity was described by the degree of opacity as clear or opaque based on the ability to read
11
closed tibial plateau fracture, were asked to be included in the research study prior to the
11
markings through a ~1cm distance through the tube. Samples were then centrifuged (3,000g for
12
procedure by an orthopaedic surgeon, and consented. A particular age range was not sought.
12
30 minutes at 4°C) to obtain discrete fractions. The relative volume of fractions was then
13
Exclusion criteria consisted of open fractures, and vulnerable groups including minors, known
13
estimated directly from the centrifuged tubes. Fluid samples were photographed before and
14
cognitively impaired or institutionalized individuals, patients with known HIV or HCV or HBV
14
after centrifugation. Following centrifugation, the supernatant and pellet were separated and
15
infections, and patients unable to provide consent.
15
stored in aliquots at -80°C. Light microscopy analysis of selected supernatants and pellets
16
Radiographs, and CT scans if available based on routine clinical care, were graded by an
16
indicated that the processing was sufficient to separate cells such that they were present in the
17
attending orthopaedic surgeon using the Schatzker classification system for tibial plateau
17
pellet and absent from the supernatant (data not shown). Samples with adequate volume (1 ml)
18
fractures 29 .
18
after processing were selected for use in the study.
19
A total of 11 synovial fluid (SF) samples collected from 8 patients were used in the present
19
Assay Validation for Biochemical Analysis of In Vitro Mixtures of SF and Blood. Due to the
20
study. Attempts were made in all consented patients for aspiration from both the injured joint and
20
blood present in the synovial fluid aspirated from patients with a tibial plateau fracture, it
21
contralateral knee. Synovial fluid samples of sufficient volume (see below) were successfully
21
was necessary to ensure that the presence of blood components in the synovial fluid did not
22
withdrawn from both the injured knee (Plat-hSF) and contralateral control knee (Ctrl-hSF) of
22
interfere with the accuracy of the biochemical assays used. Therefore, prior to biochemical
23
three donors with an acute tibial plateau fracture. For two other patients, Plat-hSF was obtained,
23

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subsequent test lubricant supplemented with PIs with the cartilage completely immersed for 16-
1
analysis of the clinical human synovial fluid samples, an in vitro model of mixtures of fresh
1
24 hours at 4°C prior to lubrication testing at room temperature. The lubricant sample and
2
EDTA-treated adult human blood (Golden West Biologicals) and human synovial fluid
2
cartilage were then tested at room temperature by preconditioning, compressing to 18% of the
3
collected during routine arthroscopic surgery was developed, in order to mimic the Plat-
3
total cartilage thickness, and allowing 30 minutes for stress relaxation and interstitial fluid
4
hSF, and used to validate the assays for protein, proteoglycan-4, and hyaluronan. First, the
4
depressurization. Then samples were rotated at an effective velocity of 0.3 mm/second with pre-
5
macroscopic appearance of in vitro mixtures of human synovial fluid and blood of varying
5
sliding durations (Tps; the duration the sample is stationary prior to rotation) of 120, 12, and 1.2
6
proportions were examined to identify variations after mixing and separation by centrifugation
6
seconds. Friction coefficients (μ) were calculated from the expression μ = ���Reff X�Neq), where
7
(3,000g for 30 minutes at 4°C). Portions of in vitro human mixtures prior to centrifugation
7
��is torque, Neq�is the equilibrium axial load after 30 minutes of stress relaxation, and Reff is the
8
(Mixture), and supernatant and pellet portions of in vitro mixtures after centrifugation were then
8
effective radius of the cartilage, as described previously 28,31 . Briefly, a static friction coefficient
9
assayed for the concentrations of total protein, hyaluronan and proteoglycan-4, relative to the
9
(μstatic) was calculated using the peak | τ |, measured immediately after (within 10° of) the start of
10
initial mixture volume. To demonstrate the visual appearance of in vitro mixtures, analogous
10
rotation, and Neq. A kinetic friction coefficient (μkinetic) was calculated using both the | τ |
11
but larger volumes (~5 ml) of bovine blood and bovine synovial fluid (Animal Technologies)
11
averaged during the second complete revolution of the test sample and also Neq.
12
were generated and photographed.
12
Consistent with previous results 31 comparing friction coefficients with increasing Tps, all test
13
Biomechanical and Biochemical Analyses of Ctrl- and Plat-hSF Samples. Portions of Ctrl-
13
lubricants demonstrated little variation in kinetic friction coefficients with values at Tps = 1.2
14
and Plat-hSF samples were analyzed by biomechanical lubrication tests for friction lowering
14
seconds remaining within 11% of values at Tps = 120 seconds; therefore, for brevity and clarity
15
properties, in addition to analysis by biochemical assays for the concentrations of total protein,
15
μkinetic data are presented as the average at all pre-sliding durations. As expected, the mean static
16
hyaluronan, and proteoglycan-4.
16
and kinetic friction coefficients measured for PBS were greater than 0.20 for all Tps, consistent
17
Analytical Methods. Lubrication Test. Portions of individual Ctrl- and Plat-hSF samples
17
with previous results 31 , so PBS data were not analyzed further.
18
were analyzed for static and kinetic friction coefficients in the boundary lubrication mode on
18
Biochemical Analyses. Portions of synovial fluid samples were analyzed biochemically for
19
articulating cartilage surfaces (one friction test per synovial fluid specimen) as described
19
absolute concentrations of lubricant molecules hyaluronan and proteoglycan-4, as well as for
20
previously 28,31 . Intact articular surfaces were in the form of osteochondral cores and annuli from
20
total protein. A minimum number of two replicate samples per specimen were used for
21
adult bovine knees, and stored in phosphate buffered saline (PBS) supplemented with protease
21
concentration measurements. Hyaluronan. The concentration of hyaluronan in SF samples was
22
inhibitors (PIs; 2 mM Na-EDTA, 1 mM PMSF, 5 mM Benz-HCL, and 10 mM NEM) at –80°C.
22
determined by an ELISA-like assay using hyaluronan binding protein (Corgenix). Proteoglycan-
23
For lubrication testing, cartilage samples were thawed at 4°C, and then bathed in ~0.5 ml of the
23

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RESULTS
1
4 (PRG4). The concentration of PRG4 in hSF samples was quantified by Western Blot using
1
Patient Demographics. A total of eleven synovial fluid samples from eight patients were
2
antibody to Lubricin after SDS-horizontal agarose gel electrophoresis on 2% 3mm thick agarose
2
used in the present study (Table I). For these patients, the tibial plateau fracture types ranged
3
gels and transfer to PVDF membrane (100mA, overnight). The immunoreactive proteins were
3
from Schatzker type II to type VI and from OTA class 41B2.2 to 41C3.3. The control group of
4
visualized by ECL-Plus detection and digital scanning with a STORM 840 Imaging System
4
normal samples (n=6) was from patients 42±16 years old (mean±SD), with a post-injury period
5
(Molecular Dynamics, Fairfield, CT). ImageQuant (Molecular Dynamics) was used to generate
5
before synovial fluid acquisition of 11±7 days. The injury group of experimental samples (n=5)
6
densitometric scans. The PRG4 in hSF was quantified using standards of PRG4 that were
6
was from patients 45±13 years old, with a post-injury period of 11±9 days. Of the eight patients,
7
purified 32 from conditioned medium of human cartilage explants and run on the same gels.
7
six were male, and two were female; both control and experimental synovial fluid samples were
8
Statistical Analysis. The data of continuous variables are presented as mean±SEM. The
8
successfully obtained from the two female patients.
9
effects of joint injury (trauma versus control) on SF properties (μkinetic and the concentration of
9
Gross Appearance of Control and Plateau Fracture Human Synovial Fluid Samples.
10
lubricants) were assessed by ANOVA. The effects of joint injury (trauma versus control, as a
10
The synovial fluid samples from the control and injured joints appeared markedly different.
11
fixed factor) and Tps (1.2, 12, and 120s, as a repeated factor) on synovial fluid static friction
11
Before centrifugation, the control synovial fluid showed only traces of blood (Fig. 1-A-i),
12
coefficient (μstatic) were assessed by two-level ANOVA. Planned comparisons for μstatic were
12
whereas the injury synovial fluid was grossly bloody (Fig. 1-A-ii). After centrifugation, the
13
performed between trauma and control groups at each Tps value. The dependencies of friction
13
supernatant of control synovial fluid samples was clarified and appeared clear or straw-colored
14
coefficients on the concentrations of putative lubricants (hyaluronan and proteoglycan-4) were
14
(Fig. 1-B-i). In contrast, the injury synovial fluid samples separated into a yellow supernatant
15
analyzed by univariate and also multivariate regression, with both the absolute and log10 value
15
and a dark red pellet of varying relative volumes (Fig. 1-B-ii).
16
of hyaluronan concentrations (since it varied by several orders of magnitude). Statistical analysis
16
Biochemical Assay Validation with in vitro Mixtures of SF and Blood. The in vitro
17
was performed using Systat 10.2 (Systat; Richmond, CA).
17
mixtures of bovine synovial fluid and bovine blood appeared similar to the range of control and
18
18
injury human synovial fluid samples. Before centrifugation, mixtures with increasing proportion
19
Source of Funding
19
of blood were of an increasingly darker shade of red (Fig. 1-C). After centrifugation, samples
20
Supported by a grant from the Orthopaedic Trauma Association, NIH R01AR051565, an
20
separated into a supernatant that was increasingly yellow and a pellet that was increasing in size
21
NSF Graduate Research Fellowship, NIH 5T35HL007491, and an award under the Howard
21
as the proportion of blood increased (Fig. 1-D). The in vitro mixtures of human synovial fluid
22
Hughes Medical Institute Professors Program.
22
23

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values were 49-120% higher for fracture synovial fluid than control synovial fluid, with the
1
and human blood appeared to separate similarly, although they were more difficult to visualize
1
percentage difference increasing as the pre-spin duration decreased from 120s to 1.2s. At the
2
due to the small volumes available.
2
short pre-spin duration of 1.2s, the μstatic values approached the μkinetic values (Fig. 3-A and B).
3
Biochemical analysis of the in vitro mixtures of human synovial fluid and blood, as well as
3
The average μkinetic value for fracture synovial fluid was double that of control synovial fluid
4
the supernatants and pellets, revealed that the hyaluronan and proteoglycan-4 constituents, when
4
(0.044 versus 0.022, p

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fluid properties were not determined. Additionally, the number of samples was limited due to
1
friction coefficients (data not shown). Multivariate regression yielded similar results (elimination
1
the relatively small number of patients meeting the inclusion criteria and consenting to the
2
of variation due to proteoglycan-4, leaving only correlation with hyaluronan concentration).
2
study. Furthermore, the control samples were not only from contralateral knees due to the
3
3
difficulty in obtaining such fluid.
4
Discussion
4
The present study expands upon previous research on the effects of human knee injuries on
5
The present study identifies marked alterations in the lubrication function and lubricant
5
synovial fluid lubricant properties by focusing on synovial fluid after tibial plateau fracture. In a
6
composition of SF from patients with intra-articular tibial plateau fractures in the initial stages of
6
previous study, synovial fluid aspirated from Emergency Department patients presenting with
7
treatment. Compared with control human synovial fluid, synovial fluid from knees with intra-
7
mono-articular knee effusions and no radiographic abnormalities (e.g., without intra-articular
8
articular fractures had markedly decreased lubrication ability (+100% increase in μkinetic, 0.022
8
fracture) also exhibited poor lubrication relative to saline (Δμ= –0.045) compared with human
9
versus 0.044) in the acute post-injury time period that was studied. Concomitantly, tibial plateau
9
control synovial fluid relative to saline (Δμ = –0.095) 33 . Though the lubrication test methods
10
fractures led to changes in the concentration of putative lubricant molecules, with a decrease in
10
were different, with the former study using a glass-on-latex arthrotripsometer versus articulating
11
hyaluronan (–87%, 2.53 mg/ml to 0.27 mg/ml) and an increase in proteoglycan-4 (+156%, 139
11
cartilage in the present study, the synovial fluid from intra-articular tibial plateau fractures also
12
μg/ml to 356 μg/ml). Regression analysis indicated that poorly lubricating synovial fluid was
12
resulted in a kinetic coefficient of friction approximately double that of the controls (Fig. 3).
13
associated with diminished hyaluronan concentration.
13
With attention to sample preparation and a previously validated boundary-mode friction
14
The experimental approach of the present study involved a number of considerations.
14
test protocol 28 , subsequent characterization of friction properties of synovial fluid at a
15
Lubrication testing of the human synovial fluid samples was performed with normal adult bovine
15
cartilage-cartilage interface can be obtained with low variability in measured friction
16
cartilage surfaces, minimizing effects of variation in cartilage surface properties. The test
16
coefficient with a coefficient of variation (CV) of 12 – 28%. However, the amount of
17
configuration facilitates boundary lubrication by apposed articular cartilage surfaces, maintaining
17
variability in the composition of the injury fluid may be due to a number of factors,
18
possible interactions between synovial fluid and the articular surfaces, and also minimizing
18
including donor age, severity of injury, days post injury that the sample was collected and
19
confounding factors such as ploughing 28 . Adult bovine cartilage appears to be lubricated
19
assay sensitivity. Thus, the lubrication properties of human knee synovial fluid may be disrupted
20
similarly by normal bovine synovial fluid (μkinetic=0.025) 31 and by control human synovial fluid
20
in a variety of scenarios of acute injury or inflammation.
21
(μkinetic=0.022, Fig. 3). Also, human synovial fluid was obtained only during surgical procedures
21
The present study is also consistent with and adds to information on the concentration of
22
under general anesthesia. These procedures occurred at various time points up to 30 days after
22
lubricant molecules in joint synovial fluid from humans and animals. The decreased
23
the injury, so the long-term and time-dependent effects of tibial plateau fracture on synovial
23

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and were present in the samples analyzed for both chemical constituents and lubrication
1
concentration of hyaluronan is consistent with effects of disease and injury of human knees 34,35 .
1
properties.
2
At the time of total knee arthroplasty, the hyaluronan concentration of synovial fluid from
2
Further studies on the components of the injury synovial fluid samples would be useful
3
osteoarthritic knees was 1.3 mg/ml 36 . Compared to these values and the control value of 2.53
3
to clarify the mechanism of altered lubrication. The structure of hyaluronan and
4
mg/ml in the present study, hyaluronan concentrations in synovial fluid from knees with tibial
4
proteoglycan-4 in intra-articular fracture conditions may affect their roles in the boundary
5
plateau fractures was markedly lower at 0.27 mg/ml. In horses, joint injury was also associated
5
lubrication of articular cartilage after joint injury. Although proteoglycan-4 levels were
6
with a decreased concentration of hyaluronan 24,37 . Studies of SF lubrication in experimental
6
higher in the plat-hSF, this elevated concentration may not have been sufficient to
7
animal injury models have focused on proteoglycan-4 25,27 but not hyaluronan. The correlation
7
compensate for the alterations in lubrication function after joint injury. Concurrently, the
8
between decreased lubrication properties and decreased HA concentration in the present study
8
structural quality of hyaluronan and proteoglycan-4 may have been compromised during
9
suggests the importance of diminished HA concentration in post-traumatic human synovial fluid.
9
injury, such as a reduction in the concentration of high molecular weight hyaluronan
10
The reported effects of injury and osteoarthritis on PRG4 concentration in humans and
10
present in the injury synovial fluid. Blood-derived components may also have contributed
11
animal models are quite varied, with some studies indicating an injury-associated decrease in
11
to deficient lubrication in plat-hSF.
12
concentration of PRG4 15,23,33 and others indicating an increase 24,38 . In osteoarthritic knees,
12
The consequences of increased friction coefficient, in the context of intra-articular
13
increasing PRG4 concentration correlated with worsening lubrication and OA severity 38 .
13
fracture and other joint injuries, remain to be fully elucidated. Increased friction and wear
14
Differences in the concentration of PRG4 in synovial fluid of human osteoarthritis (151 μg/ml)
14
appear to be related. It is possible that even a short period of deficient synovial fluid
15
and human trauma (356 μg/ml), may be due a difference in analysis methods including
15
lubrication, in the setting of soft-tissue or weight-bearing loads are sufficient to initiate
16
standards, or a difference in patient populations. Total protein levels were also markedly
16
damage that can have longer-term consequences. Studying early time points is the first step
17
different with 27 mg/ml for synovial fluid from end-stage osteoarthritic knees at the time of total
17
to studying and identifying a longer-term effect.
18
knee arthroplasty 36 , compared to 38 mg/ml in trauma knees and 22 mg/ml in control knees in the
18
The collective results here indicate that lubricant molecules in synovial fluid after a tibial
19
present study. This may be due to differences in the pathologic processes, since after trauma the
19
plateau fracture are acutely altered with diminished hyaluronan concentration, and elevated
20
joint space is compromised and SF may be diluted by extra-articular contents and infiltrated by
20
concentrations of proteoglycan-4 and total protein compared with controls. The correlation of
21
protein in blood. Although the specimens were processed to remove red blood cells, it is
21
impaired lubrication of trauma SF with diminished hyaluronan and elevated proteoglycan-4
22
likely that a considerable amount of blood components, such as serum proteins, remained
22
remains to be evaluated further. The proteoglycan-4 that is elevated may not be functional alone,
23

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1
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2
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9. Buckwalter JA, Saltzman C, Brown T. The impact of osteoarthritis: implications for
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11. Weiss NG, Parvizi J, Trousdale RT, Bryce RD, Lewallen DG. Total knee arthroplasty in
Articular fractures. J Am Acad Orthop Surg. 2004; 12:416-23.
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21. Repo RU, Finlay JB. Survival of articular cartilage after controlled impact. J Bone Joint
21.
Surg Am. 1977; 59:1068-76.
12. Civinini R, Carulli C, Matassi F, Villano M, Innocenti M. Total knee arthroplasty after
22. Hooiveld M, Roosendaal G, Vianen M, van den Berg M, Bijlsma J, Lafeber F. Blood-
complex tibial plateau fractures. Musculoskelet Surg. 2009; 93:143-7.
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13. Furman BD, Olson SA, Guilak F. The development of posttraumatic arthritis after
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23. Elsaid KA, Fleming BC, Oksendahl HL, Machan JT, Fadale PD, Hulstyn MJ, Shalvoy R,
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24. Antonacci JM, Schmidt TA, Serventi LA, Shu YL, Gastelum NS, Schumacher BL,
after injury to the cruciate ligament or meniscus. J Orthop Res. 1994; 12:21-28.
McIlwraith CW, Sah RL. Effects of joint injury on synovial fluid and boundary
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25. Teeple E, Elsaid KA, Fleming BC, Jay GD, Aslani K, Crisco JJ, Mechrefe AP.
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diarthrodial joints, in Basic Orthopaedic Biomechanics and Mechano-Biology, Mow VC,
deficient guinea pig knee. J Orthop Res. 2008; 26:231-7.
Huiskes R, Editors. 2005, Lippincott Williams & Wilkins: Philadelphia. p. 447-494.
26. Flannery CR, Zollner R, Corcoran C, Jones AR, Root A, Rivera-Bermudez MA, Blanchet
18. Swanson SAV, Friction, wear, and lubrication, in Adult Articular Cartilage, Freeman
T, Gleghorn JP, Bonassar LJ, Bendele AM, Morris EA, Glasson SS. Prevention of
MAR, Editor. 1979, Pitman Medical: Tunbridge Wells, England. p. 415-460.
cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with
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JB. The role of biomechanics and inflammation in cartilage injury and repair. Clin
27. Jay GD, Fleming BC, Watkins BA, McHugh KA, Anderson SC, Zhang LX, Teeple E,
Orthop Relat Res. 2004; 423:17-26.
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36. Mazzucco D, Scott R, Spector M. Composition of joint fluid in patients undergoing total
chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate
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Biomaterials. 2004; 25:4433-45.
28. Schmidt TA, Sah RL. Effect of synovial fluid on boundary lubrication of articular
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cartilage. Osteoarthritis Cartilage. 2007; 15:35-47.
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29. Schatzker J, McBroom R, Bruce D. The tibial plateau fracture: the Toronto experience
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1968-1975. Clin Orthop Rel Res. 1979; 138:94-104.
38. Neu CP, Reddi AH, Komvopoulos K, Schmid TM, DiCesare PE. Increased friction
30. Pascual E, Doherty M. Aspiration of normal or asymptomatic pathological joints for
coefficient and superficial zone protein expression in patients with advanced
diagnosis and research: indications, technique and success rate. Ann Rheum Dis. 2009;
osteoarthritis. Arthritis Rheum. 2010; 62:2680-7.
68:3-7.
39. Hooiveld M, Roosendaal G, Wenting M, van den Berg M, Bijlsma J, Lafeber F. Short-
31. Schmidt TA, Gastelum NS, Nguyen QT, Schumacher BL, Sah RL. Boundary lubrication
term exposure of cartilage to blood results in chondrocyte apoptosis. Am J Pathol. 2003;
of articular cartilage: role of synovial fluid constituents. Arthritis Rheum. 2007; 56:882-
162:943-51.
91.
40. Jansen NW, Roosendaal G, Wenting MJ, Bijlsma JW, Theobald M, Hazewinkel HA,
32. Schumacher BL, Block JA, Schmid TM, Aydelotte MB, Kuettner KE. A novel
Lafeber FP. Very rapid clearance after a joint bleed in the canine knee cannot prevent
proteoglycan synthesized and secreted by chondrocytes of the superficial zone of
adverse effects on cartilage and synovial tissue. Osteoarthritis Cartilage. 2009; 17:433-
articular cartilage. Arch Biochem Biophys. 1994; 311:144-52.
40.
33. Jay GD, Elsaid KA, Zack J, Robinson K, Trespalacios F, Cha CJ, Chichester CO.
Lubricating ability of aspirated synovial fluid from emergency department patients with
knee joint synovitis. J Rheumatol. 2004; 31:557-564.
34. Asari A, Miyauchi S, Sekiguchi T, Machida A, Kuriyama S, Miyazaki K, Namiki O.
Hyaluronan, cartilage destruction and hydrarthrosis in traumatic arthritis. Osteoarthritis
Cartilage. 1994; 2:79-89.
35. Praest BM, Greiling H, Kock R. Assay of synovial fluid parameters: hyaluronan
concentration as a potential marker for joint diseases. Clin Chim Acta. 1997; 266:117-28.

Effect of Tibial Plateau Fracture on Page 25 of 25
Lubrication Function and Composition of Synovial Fluid 8/22/2011
Effect of Tibial Plateau Fracture on Page 24 of 25
Lubrication Function and Composition of Synovial Fluid 8/22/2011
Figure 4. Effect of tibial plateau fracture on (A) hyaluronan, (B,C) proteoglycan-4, and (D)
TABLE LEGENDS
protein. (A,C,D) Concentrations were determined for synovial fluid from control (Ctrl-hSF, n=6)
Table I. Summary of donor demographics. Tibial plateau fractures are categorized according
or fractured (Plat-hSF, n=5) knees. Data are Mean±SEM. * indicates p

CME Question(s) Provisionally Accepted Manuscripts Only
Acknowledgement
CME Questions
Acknowledgments
1. Proposed mechanisms of post-traumatic arthritis do NOT include
a. enzyme-mediated cartilage degradation
b. articular chondrocyte death and cartilage damage due to direct trauma
c. reactive oxygen species
d. synovial fluid electrolyte abnormalities
e. impaired lubrication
Vedant Kulkarni, MD, Jonah Hulst, MD, Hugo Sanchez, MD, Suzanne Steinman, MD, UCSD
orthopaedics residents, graciously contributed to clinical sample acquisition for this study. This
work was supported by a grant from the Orthopaedic Trauma Association (BLB), NIH
R01AR051565 (RLS), an NSF Graduate Research Fellowship (JMA), NIH 5T35HL007491 (for
Page 4, lines 14-17: “Recent studies have focused on articular chondrocyte death and
cartilage damage due to direct trauma, enzyme-mediated cartilage degradation, and the
role of reactive oxygen species 13-16 . Deficient lubrication may also contribute to cartilage
deterioration after trauma.”
AYH), and an award to the University of California, San Diego under the Howard Hughes
Medical Institute Professors Program (for RLS).
2. In the early (day 1-30) period after tibial plateau fracture, synovial fluid exhibits a
a. decrease in lubrication properties
b. decrease in hyaluronan concentration
c. decrease in PRG4 (lubricin) concentration
d. decrease in total protein concentration
e. decrease in RBC count
Page 13, lines 2-9: “The concentration of hyaluronan was markedly lower in fracture
synovial fluid than control synovial fluid (0.27 mg/ml versus 2.53 mg/ml, –87%,
p460 kDa in synovial fluid samples (Fig. 4-B), the concentration
of proteoglycan-4 was markedly higher in fracture synovial fluid than control synovial
fluid (356 versus 139 μg/ml, +156%, p

Figure 1
Click here to download high resolution image
1 1 1 III 41B2.2 7 1 of 1 ORIF 25 F pedestrian v. auto
2 2 2 V 41C3.3 8 1 of 2 ex fix 55 M fall from fence
3 3 3 II 41B3.1 11 2 of 2 ORIF 57 F motor vehicle accident
4 4 V 41C3.3 20 2 of 2 ORIF 57 M loading dock box crush
5 5 VI 41C3.3 10 2 of 2 ORIF 25 M altercation
6 6 II 41B3.3 8 1 of 1 ORIF 31 M fall from telephone pole
7 4 V 41C3.3 27 1 of 1 ORIF 44 M soccer
8 5 II 41B3.1 3 1 of 1 ORIF 42 M ATV acccident
Gender Trauma Mechanism
Age
Procedure
Type
Procedures
Procedure #
of Total # of
Day
Postinjury
Schatzker OTA
Classification
#
Trauma
Sample
#
Control
Sample
Donor
#
Table I

Figure 3
Click here to download high resolution image
Figure 2
Click here to download high resolution image

Figure 5
Click here to download high resolution image
Figure 4
Click here to download high resolution image

OSTEOCHONDRAL
GRAFTING
WHO,WHEN,WHERE,WHY,& HOW
12/17/2010
Ralph A. Gambardella, MD
Kerlan-Jobe Orthopaedic Clinic
Los Angeles, California
Treatment Options
Presentation Goals
• Review of Clinical History
• Review of Bioengineering History
• Review of Surgical Technique
Surgical Options
• Lavage, debridement
• Drilling, abrasion, microfracture
• Osteochondral autograft g
• Chondrocyte Implantation
• Osteochondral allograft
12/17/2010
1

WHO ?
• NO age limit
• Generally under the age of 50 years
• Focal Focal, full thickness articular cartilage
defects
WHEN ?
• Defect size variable in the literature
–One cm
– Five cm
• Literature supports best results in young
• Femoral Condyle> Trochlea> Patella
WHEN ?
• Most often after failed debridement and or
microfracture
• Appropriate as the initial surgical treatment
of focal full thickness lesions
WHEN ?
• Osteochondritis Dissecans
• More Controversial
– Osteonecrosis
– Osteoarthritis
2

WHERE ?
ANYWHERE
• Knee
• Ankle
• Shoulder
•Hip
WHERE ?
WHY ? Osteochondral Autografts
• Non-inflammatory healing response
• Fill defects with osteochondral bone graft
• Favorable results at 7-10 years
• Immediate access to graft
• Minimally-invasive procedure
12/17/2010
3

WHY ?
CLINICAL STUDIES
Bobic (1995)
• Condyle lesion with ACL injury
• Arthroscopic technique with ACL
reconstruction
• 29 patients with >1cm lesion
• 19/22 excellent results @ 2-3 year followup
• Hyaline cartilage biopsy specimens
Autograft Development
• Open mosaicplasty
– Hangody
• Open/arthroscopic OATS
– Bobic
• Open/arthroscopic COR
– Barber-Chow
Hangody (1997)
• Preliminary report
• 44 patients
• Open technique with autograft
• Open technique with autograft
• HSS score
–Pre: 62
– Post: 94
4

Hangody Results
• Multicenter prospective study
• 417 patients
• 1992 to 1996
• Arthroscopic technique
• Femoral condyle lesions
Hangody 2004 JBJS
• 831 Patients
• Up to 10 year follow-up
• Good to excellent results:
– 92% Femoral
– 87% Tibial
– 79% Trochlear and Patellar
– 94% Talar Dome
Post-op Improvement
Modified Cincinnati Knee Score
1 year 3 year 5 year
Abrasion 58 % 28 % 0 %
Microfracture 57 % 33 % 34 %
Drilling 21 % 33 % 34 %
Mosaicplasty 89 % 88 % 87 %
Hangody 2004 JBJS
• 3% morbidity
• 69 of 83 second look
arthroscopy with
congruent surface and
viable chondrocytes
with histology
5

Hangody 2004 JBJS
• Histologic evidence of
long term graft
survival
• Fibrocartilage filling
of donor sites
Marcacci 2005 Arthoscopy
• 37 patients in a prospective study
• 2 year f/u
• 78 % good to excellent using ICRS Score
• Young patients and LFC lesions did the best
Hangody 2004 JBJS
• Recommendations
– Defects 1-4 square cms. in size
– Attention to detail in technique
– Upper limit age of 50 yrs
WHY ?
BASIC SCIENCE
STUDIES
6

Bioengineering Concerns
• Proud Plug
– Sees increased joint load
– Progressive loss of surface
– Damage to opposing surface
• Recessed Plug
– Sees decreased joint load
– Integration of soft fibrous tissue
– Decreased nutrition (fluid – bone)
Topographic Considerations
Osteochondral Grafting
Ahmad et al AOSSM March 2001
• Donor Sites
– Medial trochlea, lateral trochlea, intercondylar notch
• Small nonloading region
• Si Similar il cartilage il thickness hi k (2.1mm (2 1 ave.) )
• Recipient Sites
– Lateral and medial trochlea curvature best match for
femoral condyles
– Intercondylar notch curvature best match for central
trochlea
– Cartilage thickness (2.5mm ave.)
Topographic Matching for
Osteochondral Grafting
Bartz et al AOSSM March 2001
• Loadbearing condylar recipient sites
– MMost tmedial di l or lateral l t lpatellar t ll groove donors d are bbest t
– Most inferior groove donor site provides best match
• Intercondylar notch donor sites
– Accurate surface restoration for 4-6mm defects
– Inadequate surface restoration for >8mm defects
Cole 2002 AOSSM
• Contact pressure at donor site of
patellofemoral joint
• Pressure is not uniform
Pressure is not uniform
• Pressure is higher on the lateral condyle
• Harvest grafts from medial condyle
7

Koh 2002 AOSSM
• Graft height mismatch
• Small incongruities lead to significantly
elevated contact pressures
– 0.5mm proud worse than 0.5mm sunk
Bioengineering Concerns
Evans 2004 Arthroscopy
• Manual versus Power Punch for Harvest
• Chondrocyte viability better with the use of
a manual punch
Burks 2002 AOSSM
• Pressure changes from defects in femoral
condyle dl
• 15mm diameter leads to 150% increase in
pressure transference to normal cartilage
Bioengineering Concerns
Lane 2004 AJSM
• Goat 6 Month Study
• Cleft between host and transferred region
remains
8

Bioengineering Concerns
Huntley 2005 JBJS
• Chondrocyte Death From Graft Harvesting
– Fresh human tissue
– Confocal microscopy
• Central 99 % viable
• 382 micron margin of cell death
• No change in 2 hours
Autograft Systems
•COR
• OATS
• Mosaicplasty
• DBCS
HOW ?
Cartilage Repair System
NEW GENERATION IN OSTEOCHONDRAL TRANSPLANTATION
Improved Accuracy
Reproducible and focused graft harvest and
drilling with a first-of-kind perpendicularity device
Protecting Chondrocyte Viability
“No impact transfer” & “Low impact delivery”
Ease of Use
Intuitive handling and efficiency
combined in a completely disposable system
9

Improved Accuracy
Harvester and Drill Guide w/ Perpendicularity
Rod
Cutting
Tooth
Underscores
Graft
Ensures
complete
uniform plug
Ease of Use
Improved Drill Bits 5mm-20mm
depth
Spade Cutting Tip
• Single Use guarantees
sharp tip
• Minimizes tip wandering
and cartilage damage
Fluted Channels
• Reduces drilling force
by removing bone
• Reduces friction and heat
that may cause cell damage
COR Precision Targeting… Easy to Use System
INTUITIVE HANDLING – Easily identified components – labeled and color coded
EFFICIENCY – Complete disposable system always available, no missing parts, no
sterilization
Protects Chondrocyte Viability
Protecting Chondrocyte Viability with “No Impact
Transfer”
Harvester/Delivery Guide Cutter
Interface
• Preloaded System
• Cutter protects and stores plug outside the
guide tube until ready for transfer
• No contact with cartilage surface at any time
Technique Keys
• Perpendicular graft insertion
• Joint congruity restoration
8
5
Graft Loader
• No impact on cartilage surface
• Single step
• Loads plug with minimal
force on cancellous bone
10

Indications
• Contained lesion
• 1cm to 3cm defects
• Normal mechanical alignment
• No kissing lesions
THE
FUTURE
Contraindications
• Osteoarthritis
• Instability
• Patellar maltracking
• Mechanical malalignment
Ideal Cartilage Scaffold
• Synthetic and biodegradable
• Designed to match the physical and mechanical
properties of the recipient tissue
• Integrates to reproduce the native properties of
articular cartilage
– Biomechanical
– Histological
– Biochemical
• Safe, effective and durable results
– IKDC, Cincinnati, KOOS or other validated measures
– MRI and/or similar quantitative assessments
– Minimal adverse events, reoperations and failures
11

Synthetic Osteochondral
Grafting
OBI
SMITH &
NEPHEW
OBI Implant Design
• OBI's multilayered product
addresses the three critical
portions of osteochondral
healing:
– articular cartilage
– tidemark
– subchondral bone
• Each layer is designed to match
the physical and mechanical
properties of the adjacent tissue
articular cartilage
tidemark
subchondral bone
Patent 5,607,474 plus others issued and pending
TruFit Surgical Technique
12

Defect
Preparation of Recipient Site
BGS Plug - Case Study
Plug Implantation
9.0 mm
�� ~ 88 % of treatment site had filled with cartilage
�� Excellent integration with surrounding
�� Normal thickness, homogeneous neocartilage
2 nd Look - 8 months
2.0 mm
Presented by David Caborn, M.D.
Original implant margin
Original implant margin
BGS Plug - Case Study
2nd Look Arthroscopy at 8 months
57-76
51-80
�� Indentation Stiffness measured
with ACTAEON ACTAEON Probe
�� Normal stiffness over 65 65-70% 70% of
original defect area
�� Stiffness above 55 shown to be hyaline (Bae Bae et al, Arth & Rheum 2003 2003)
�� Directly comparable to animal study at same timeframe
Presented by David Caborn, M.D.
13

BGS Plug - Case Study
3 rd Look - 21 months
Original implant margin
�� Entire site had filled with cartilage with
smooth integration
�� Cartilage stiffness of repair and
surrounding tissue within normal range of
hyaline cartilage
�� Area of fibrillation caused by meniscal tear
Presented by David Caborn, M.D.
2007 ICRS WARSAW
Cartilage Repair with TruFit CB
Plug
Spaulding, et.al.
• 8 patients
• Failed debridement or microfracture
• IKDC from 44.6 to 79
• 8 month f/u
Biopsy:
anterior area of
treated site
near center
Saf O/Fast Green shows normal
hyaline like cartilage and
complete subchondral bone fill
BGS Plug - Case Study
3 rd Look - 21 months
Original implant margin
Presented by David Caborn, M.D.
2007 ICRS WARSAW
TruFit Early Results
Sciarretta, et.al.
• 15 patients
15 patients
• 11 mm plugs
• Early improvemrnt with IKDC scoring
14

Point-of-Care Cell Therapy:
Autologous Tissue Repair and
RRegeneration ti
Regenerative Medicine at Johnson & Johnson
CAIS Point-of-Care Cell Therapy
1: BIOPSY
Harvest/Mince Small Tissue Sample
Tissue Loaded
Scaffold
Holding Ring
2: AUTOGRAFT PREPARATION
Fibrin Glue
(Crosseal)
3: SURGICAL IMPLANTATION
Minced tissue
loaded scaffold
+
Disposable Patient Kit:
• Harvesting tool
• Loading Device
• Proprietary Scaffold
• Fixation Staples
Staple
J&J’s Intraoperative, Point-of-Care,
Cell Therapy Paradigm (CAIS)*
Harvest
Same day
Implantation
CAIS DEVICE KIT
Minces tissue
Prepares Implant
*(Cartilage Autograft Implantation System)
CAIS Preclinical Evidence
(Goats and Horses)
• Surgically created, clinically relevant cartilage defects
– Goat: 7 mm diameter, one staple fixation
– Horse: 15 mm diameter, three staple fixation
Implant
Goat
Horse
15

Controlled Rehabilitation in Horses:
Progressive Treadmill Exercise
30 mph Gallop at 6 Months
Histological Analysis of Repair Tissue
Goats (6-mos)
Empty
untreated
Scaffold
alone
CAIS
Horses (12-mos)
Repair Site Appearance
CAIS: one stage procedure
(Horse) at 12 Months
0 5 10 15 mm
Two stage procedure Empty
• CAIS provides excellent fill, uniformity and
integration of repair tissue with the host
CONCLUSIONS
16

Indications
• Contained lesion
• 1cm to 3cm defects
• Normal mechanical alignment
• No kissing lesions
FUTURE NEEDS
• More clinical studies
• Long term
• MRI evaluations
• Bone scan evaluations
• Ultrasound evaluations
• Computerized mapping techniques
Contraindications
• Osteoarthritis
• Instability
• Patellar maltracking
• Mechanical malalignment
FUTURE NEEDS
• More basic science studies
–Stiffness and biomechanical
studies
–Edge integration studies
–Plug depth and Press-fit stability
–Pulsed Electromagnetic field
studies
17

THANK YOU
18

� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety
� Human Clinical Trials
Efficacy
� Future
CAIS and Allogeneic
Transplantion: Clinical
trials
Bert R. Mandelbaum MD DHL
(hon)
FIFA Medical Committee
F-MARC Member
Team Physician US Soccer, LA Galaxy,
Chivas USA, Pepperdine University
CAIS
Overview
Historical Overview
Evolving Concepts/Technology 2009
Autologous Chondrocye Implantation
� 1982-Grande, Peterson Rabbit
study
�� 1987 1987- Clinical Application in
Gothenburg Sweden
� 1996- Carticel Registry
� 2000 -Multiple Labs, new scaffolds
� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety and Efficacy
� Rehabilitation and postoperative
care
� Future
1st Surgery: Su ge y
Harvest
Day 1 Transport
& Process Tissue
CAIS
Overview
ACI Generation l Paradigm:
Complex Two-Stage Procedure
Day 28+:
2 nd Surgery:
Implantation
� 2002-07
Day 28
Transport Day 24
Cell Isolation Expansion
Day 2
Day 23
Formulation
Historical Overview
Evolving Concepts/Technology 2012
Autologous Chondrocye Implantation
� RCT microfracture equivalence
JBJS 2004 /2007
Packaging
ChondroCelect vs MFX
� 2007-2011 Landmark StudiesKOOS
Clinical benefit at 36m
30
� Trochlear, Patella, youth, athletes
20
� 10-20 year outcomes
� RCT superiority over MFX
10
0
BL 6M 12M 18M 24M 30M 36M
1

Generation l
Conclusions
Favorable factors for ACI:
1. Younger patient
2. High pre-op. clinical score
3. Duration

� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety and Efficacy
� Rehabilitation and postoperative
care
� Future
1: BIOPSY
Harvest/Mince Small Tissue Sample
Tissue Loaded
Scaffold
Holding Ring
2: AUTOGRAFT PREPARATION
Cartilage Alone
CAIS
Overview
CAIS
Technique
Fibrin Glue
(Crosseal)
3: SURGICAL IMPLANTATION
Minced tissue
loaded scaffold Staple
+
Disposable Patient Kit:
• Harvesting tool
• Loading Device
• Proprietary Scaffold
• Fixation Staples
Tissue Specific Response
SCID Mouse
Bone/cartilage Paste
In Vitro
H/E
IIn Vi Vivo
Saf-O
In Vivo
MMAB
Cartilage Alone
Bone/cartilage Paste
Cartilage Autograft Implantation
System (CAIS) DePuy Mitek J & J
Harvest
Same day
Implantation
CAIS DEVICE KIT
� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety and Efficacy
� Rehabilitation and postoperative
care
� Future
CAIS
Overview
Minces tissue
Prepares Implant
Cole, Farr, Hosea, Richmond,
Gambardella Mandelbaum
Clinical Trial 2006-07
30 pateints complete March
31,2007
CAIS Preclinical Evidence (Goats
and Horses)
�Surgically created, clinically relevant cartilage
defects
�Goat: 7 mm diameter, one staple fixation
�Horse: 15 mm diameter, three staple fixation
Goat
Implant
Horse
3

Controlled Rehabilitation in
Horses:
Progressive Treadmill Exercise
30 mph Gallop at 6 Months
CAIS
Histological Analysis of Repair Tissue
Goats (6-mos)
Horses (12-mos)
Empty
untreated
Scaffold
alone
CAIS
Summary of Goat and Horse
Study
Efficacy
� Good integration with adjacent
cartilage and bone
� Cartilage loaded implant performed
better than scaffold alone and empty
ddefect f t
� Long term under strenuous
mechanical challenge in horses at
12 months
� More consistent fill
� More uniform saffranin-O staining
� More hyaline-like appearance
� phenotypic expression of cartilage
markers: Type II vs Type I collagen
CAIS
Morphologic Repair (Horse) 12m
CAIS: one stage procedure
0 5 10 15 mm
Two stage procedure Empty
�excellent fill, uniformity and lateral and basal
integration of repair tissue
CAIS
Immunostaining (goats) 6 months
Tissue
+
Scaffold
Scaffold
alone
Summary of Goat and Horse
Study
Safety
� No adverse events
� graft preparation,
� surgical implantation,
� post-implantation rehab
� clinical examinations
� final necropsy analysis
� Biocompatible
Type I
Type yp II
Type I
Type II
4

� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety and Efficacy
� Rehabilitation and postoperative
care
� Future
CAIS
Overview
Articular Cartilage lesions (Grade lll-IV +OCD
full thickness)
1-8 cm2
Repair Options
� Cellular/Biologic
Transplantation (ACI)
� Periosteum
� scaffolds (HA, collagen MACI,
PLA/PGA fleece) with
chondrocytes
X-rays
Key Milestone: Clinical Trial
Initiation
� Internal development program at
DePuy Mitek and JNJ
Regenerative Therapeutics
� Ongoing g g IDE Clinical study y
� Randomized Controlled Multi-center
� 6 sites
� Ongoing EU clinical study
� Randomized Controlled Multi-center
� 6 countries
CAIS
Case History
Before After
Large focal defect before and after
implant placement using CAIS
�44 y/o male
�Twisted R knee getting out of bed 1-05. He
developed R knee pain, locking and mechanical
symptoms. t
�MRI R knee revealed OCD lesion of MFC
�6-05 underwent arthroscopic debridement and
chondral biopsy followed by ACI 9-05.
�R knee has done well
MRI
5

� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety and Efficacy
� Rehabilitation and postoperative
care
� Future
� Weeks 6-12
CAIS
Overview
CAIS Post Operative and
Rehabilitation Program
� Advance to FWB as tolerated
�Discard crutch when pain free and gait pattern
normalizes
�� Discontinue brace when quad control achieved
� Gain full A/PROM
� Begin with open chain isometrics, progress to
closed chain through pain free arc of motion;
resistance less than patient’s body weight.
Balance, proprioception, PRE hamstrings, calves,
hips, upper quadrant.
AJSM 2012
Summary Cole, Farr, Mandelbaum of Goat et and al Horse
Study
Safety
� No adverse events
� graft preparation,
� surgical implantation,
� post-implantation rehab
� clinical examinations
� final necropsy analysis
� Biocompatible
Change from Baseline
60
40
20
0
CAIS Post Operative and
Rehabilitation Program
�Weeks 0-2
�TDWB, brace locked in full extension
�Begin CPM post-op
�6-8 hours/day, 0-45� advance to 90� as tolerated
�Weeks �Weeks 22-6 6
�TDWB, brace unlocked
�Continue CPM through week 3
�Increase PROM as tolerated
�Weeks 0-6
�Isometric quad strengthening, SLR, Hip abd/add,
hamstring isometrics, stationary bike for PROM
CAIS Post Operative and Rehabilitation
Program
� 12 weeks and beyond
� FWB with normalized gait pattern
� No brace
� Full pain-free AROM
� 3-6 months
� Treadmill walking, g, bilateral closed chain exercises as tolerated, ,
progression of stationary bike resistance, Stairmaster

� Overview
� Previous experience
�� Rationale for CAIS
� Animal study
� Human Clinical Trials
Safety and Efficacy
� Rehabilitation and postoperative
care
� Future
CAIS
Overview
Autologous vs Allogeneic Cells
• Autologous Cell-based Technologies
- Advantages
o No disease transmission concern
o No immuno-rejection j concern
o No donor tissue/cell shortage issue
- Disadvantages
o Repair efficacy with autologous tissue or cell grafts is
effected by the age of the patient
o Donor site morbidity concern
o Limited availability of autologous donor tissue/cells
o Two surgeries are required in the case of autologous
cultured chondrocyte implantation
Clinical Literature Related to
Immunological Properties of Cartilage Allograft
� Cartilage is immune privileged
– Gibson et al. Brit J Plast Surg 1958; 11:177
� Three decades of success with fresh osteochondral allograft
transplantation – immune suppressive agents g not required
– Gross (Clin Orthop Relat Res. 2005 435:79-87)
– Bugbee (J Knee Surg. 2002 Summer;15(3):191-5)
– Convery (Clin Orthop Relat Res. 1991:(273):139-45)
� Osseous component occasionally could give rise to moderate
immunologic reaction
– Elves & Zervas Br J Exp Pathol 1974; 55:344-351
� Pivotal study
CAIS
Future
� Profiling and stratification of patients,
timing and other cohort details
� Arthroscopic techniques
� Other technologies in conjunction
…growth factors
Autologous vs Allogeneic Cells
• Allogeneic Cell-based Technologies
- Advantages
o No donor site morbidity issue
o Si Single l surgery
o Possible to obtain tissues/cells younger than patients’ own
tissues/cells
- Disadvantages
o Disease transmission concern (actual risk is very low)
o Immuno-rejection concern (actual risk is very low)
o Donor joint supply limitation
Immune-privilege of Juvenile Chondrocytes
H. Nochi, P.R. Streeter, C. Milliman C, K.A. Hruska and H.D. Adkisson (2004),
Transaction of the 50 th Annual Meeting of Orthopaedic Research Society
San Francisco, CA. p.594
Mixed lymphocyte reaction (MLR) assay was conducted to determine the proliferation of human
peripheral blood lymphocytes when co-cultured with allogeneic human juvenile chondrocytes.
Key y findings g from the study y are:
• Juvenile chondrocytes do not elicit an allogeneic immune response.
• Juvenile chondrocytes lack the expression of specific co-stimulatory molecules required for
alloreactivity.
• Juvenile chondrocytes express cell surface proteins that suppress lymphocytes proliferation.
7

Adult vs Juvenile Cells
Juvenile cartilage cell density ≈ 10 x Adult cartilage cell density
Juvenile Cartilage Adult Cartilage
Tissue Engineered Cartilage Grafts with Allogeneic
Juvenile Chondrocytes
(DeNovo ® ET)
Developed by Zimmer, Inc. and ISTO Technologies, Inc.
(under clinical investigation in the US; not approved for sale in US or European
Union)
Cell Morphology and collagen fibrillar structure
Native Juvenile cartilage
Juvenile Adult DeNovo Neocartilage ET
Native Tissue Engineered Tissue DeNovo ET
Adult vs Juvenile Cells
Juvenile cells have better biosynthetic activities
S-GAGG/DNA/Day
3
2
1
0
0 10 20 30 40 50 60 70 80
Age (years)
J. Feder, H.D. Adkisson, N. Kizer, K.A. Hruska, R. Cheung, A. Grodzinsky, Y. Lu, J. Bogdanske and M. Markel (2004)
In: Tissue Engineering in Musculoskeletal Clinical Practice (eds. L. Sandell & A. Grodzinsky),
American Academy of Orthopaedic Surgeons, Rosemont, IL, pp.219-226
DeNovo ET Implant: What is it?
� Cartilage allograft grown with juvenile human chondrocytes
(NO FETAL OR STILL-BORN INFANT TISSUES/CELLS ARE USED)
� Secured Juvenile Donor into cartilage Minced defects with a fibrin adhesive
Tissue
Tissue
Digestion
Primary Cells
Thaw and Seed
Released Cells
Expansion
Culture
Expanded Cells
Implant
Culture
No scaffold
Cryo-Preserve
NC lot # 1
NC lot # 2
NC lot # 3
NC lot # 4
Donor “Cell Bank”
DeNovo ET graft characteristics
• intense staining for GAG indicating the abundance
of proteoglycans in the extracellular matrix
• Biochemical composition indicative of hyaline cartilage
� Type II, VI, IX and XI collagens deposited in the ECM
� No measurable Type I or X collagen in the ECM)
DeNovo ET
8

Allogeneic Particulated Cartilage Graft
(DeNovo ® NT)
Processed by ISTO Technologies, Inc.
Marketed by Zimmer, Inc.
(only available to surgeons in US currently in a limited release)
(not approved for sale in the European Union)
DeNovo NT Allograft Cartilage
THANK YOU
Bert R. Mandelbaum MD DHL
What is it?
� Cartilage tissue allograft composed of juvenile donor hyaline cartilage
pieces
� Mechanically minced with a high cell viability
� Secured into cartilage defects with a fibrin adhesive
Juvenile Donor Joint Minced
DeNovo NT Implant
Tissue
Frisbie et. al. (2006)
(a) DeNovo NT human cartilage graft
(b) Implanted in chondral defects of the horse knee
(c) Good qualities of both cartilage repair tissue and subchondral bone
6-month horse study
9

Osteochondral Allograft
Transplantation:
Basic Science
William Bugbee, MD
Att Attending di Ph Physician, i i Scripps S i Clinic Cli i
Associate Professor
Department of Orthopaedics
University of California, San Diego
Governing Principles for
Osteochondral Allografting
• Whole tissue or organ transplant
• Viable chondrocytes
• Mature hyaline cartilage matrix
• Chondrocytes survive
transplantation and maintain
matrix
• Cells within matrix are
immunopriveleged
How Do We Establish These
“Governing Principles”?
Basic Science Collaboration
David Amiel, PhD
Connective Tissue Biochemistry Lab
Department of Orthopedics, UCSD
Robert Sah, MD, ScD
Cartilage Tissue Engineering Lab
Department of Bioengineering, UCSD
Basic Science
• Historical Context
• Surgical technique
• Immunology
• Disease transmission
• Retrieval analysis
• Allograft recovery and processing
• Allograft storage
• Fresh vs Frozen
• Tissue engineering with allografts
Governing Principles for
Osteochondral Allografting
• Osseous portion is a nonliving
osteoconductive scaffold
• Interface for attachment and
integration
• Transplant p minimal bone volume
necessary for restoration or fixation
• Graft incorporates by creeping
substitution
• Potential site for immunologic
response
• Behavior of osseous component is
most important factor in clinical
outcome
Fresh Allograft
Recovery and Processing
• Before 2002
– Institution associated tissue banks
– “Exceptional release criteria”
– IRB, independently developed recovery,
processing and release protocols
– Recovery y to implantation p less than 7 days y
– Less than 100 per year
• After 2002
– Commercial distribution by national tissue
banks
– Standardized protocols, AATB and FDA
oversight (CFR 1271)
– Recovery to implantation 7-42 days
– More than 2000 per year
1/23/2012
1

“Logistics” of Osteochondral
Allograft Transplantation
Donor
Patient
• Donor recovery
• Evaluation and indication
• Donor suitability
• Consent and counseling
evaluation
• Communication with
• Processing and testing tissue bank
• Graft storage
• Anatomic sizing
• Donor and recipient • Insurance approval
matching
• Patient notification of
• Final graft release
potential donor
• Shipping
• Graft release
• 28 day window to implant • Surgical scheduling
Fresh Osteochondral Allografts are
More Effective than Frozen
Osteochondral Allografts in Repair
of Cartilage Defects in the Goat
*Andrea L Pallante, ‡Simon Görtz, +Won C Bae,
*Albert C Chen, ‡Derek Chase, ‡Scott T Ball,
+Christine B Chung, +Graeme M Bydder, ‡David Amiel, *Robert L Sah, ‡°William D
Bugbee
University of California-San Diego,
Departments of *Bioengineering, +Radiology, ‡Orthopaedic Surgery, La Jolla, CA
°Scripps Clinic, Division of Orthopaedic Surgery, La Jolla, CA
Department of
Bioengineering
skeletally,
mature goat, n = 8
Non-OPERATED OPERATED
O = 8 mm
h = 5 mm
Experimental Design
MFC
Treatment Storage
Time [d]
MFC
n
LT
n
Non-OP ── 8 8
FROZEN ── 4 4
FRESH 3 4 4
LT
harvest donor cores
+
mark k & ddrill ill recipient i i t sites it grafted ft d knee k
LT
1 cm
MFC
=
Chondrocyte Viability
• Living chondrocytes are the fundamental basis
for fresh allografting
• Maintenance of intact hyaline cartilage matrix
(fresh vs. frozen)
• Long term graft function
Allograft Efficacy May Be Dependent on
Viable Chondrocytes & Mechanical Stability
• retrieved fresh grafts
– patients required revision/TKA � bias
– contain viable cells up to 29 yrs after implant 1
– failures demonstrate: 2
low # chondrocytes ↑ surface f roughness necrotic ti bbone
articular surface
articular surface
cartilage
tidemark
• pannus-like covering, subchondral irregularities3 H & E
Saf-O bone H & E
1Jamali+ 2007. 2Gross 2008. 3Williams+ 2007.
Goat Knee Analysis (6 months)
STRUCTURE: MRI
• en bloc knee samples
• clinical sequences
– T1w: T1-weighted w/o fat saturation
– T2w FS: T2-weighted w/ fat saturation
STRUCTURE: Gross Grade
1 cm
Non-OPERATED OPERATED
LT
Harvest Plugs LT
MFC
MFC
HOST GRAFT HOST
T1w T2w FS
Loadd
1 cm
TISSUE MATRIX:
Indentation Stiffness
Time
CHONDROCYTE
VIABILITY &
CELLULARITY
• LIVE/DEAD: vertical & en face
TISSUE MATRIX:
mCT
• w/ Hexabrix
contrast
Histology
•H & E
•Saf-O
1/23/2012
2

LIVE
DEAD
LIVE+DEAD
Viability in Grafts @
t=0 (implant)
100 μm
FROZEN
FRESH
LIVE
DEAD
LIVE+DEAD
Reflects Cell Content @
t = 6 months
Non-OP
250 μm
FROZEN
FRESH
Media Optimization for the Storage
of Fresh Osteochondral Allografts
• Ongoing translational research project
• Collaborative, interdisciplinary
• NIH supported t d
• Now part of standardized tissue bank recovery
and processing protocols
• Partially solved graft availability problem
• Facilitated osteochondral transplantation surgery
outside of specialized centers
% Viability V
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
FBS versus SFM: Viability by Layer
superficial
middle
deep
Day 1 Control Day 28 SFM Day 28 FBS
MFC
LT
Frozen Grafts Exhibit ↓
Matrix Content
Non-OP FROZEN
FRESH
Allograft Storage Studies
2002-2010
• Williams SK, Amiel D, Ball ST, Allen RT, Wong VW, Chen AC, Sah RL, Bugbee WD: Prolonged
Storage Effects on the Articular Cartilage of Fresh Human Osteochondral Allografts. J Bone Joint
Surg Am 85-A(11):2111–20, November 2003.
• Ball ST, Amiel D, Williams SK, Tontz W Jr., Chen A, Sah RL, Bugbee WD: The Effects of Storage
on Fresh Human Osteochondral Allografts. Clin Orthop Relat Res (418): 246–56, January 2004.
• Allen RT, Robertson CM, Pennock AT, Bugbee WD, Harwood FL, Wong VW, Chen AC, Sah RL,
Amiel D: Analysis of Stored Osteochondral Allografts at the Time of Surgical Implantation. Am J
Sports p Med 33(10):1479–94. ( ) October 2005.
• Pennock AT, Robertson CM, Wagner F, Harwood FL, Bugbee WD, Amiel D: Does Subchondral
Bone Affect the Fate of Osteochondral Allografts During Storage? Am J Sports Med 34(4):586–
91, April 2006.
• Robertson CM, Allen TR, Bugbee WD, Harwood FL, Healey RM, Amiel D: Upregulation of
Apoptotic and Matrix-related Gene Expression During Fresh Osteochondral Allograft Storage.
Clin Orthop Relat Res 442:260–66, January 2006.
• Pennock AT, Wagner F, Harwood FL, Bugbee WD, Amiel D: Prolonged Storage of
Osteochondral Allografts: Does the Addition of Fetal Bovine Serum Improve Chondrocyte
Viability? J Knee Surg 19(4):265–72, October 2006.
• Pallante AL, Bae WC, Chen AC, Görtz S, Bugbee WD, Sah RL: Chondrocyte Viability is Higher
after Prolonged Storage at 37°C than at 4°C for Osteochondral Grafts. Am J Sports Med., October
2009
Superficial
Middle
Deep
Day 1 Day 28 SFM Day 28 FBS
1/23/2012
3

CPM/mg Carrtilage
80.0
70.0
60.0
50.0
40 40.00
30.0
20.0
10.0
0.0
600
500
400
300
200
100
0
Proteoglycan Synthesis
35 SO4 Uptake
Day 1 Day 7 Day 14 Day 28
Williams et al., JBJS Am 2003
Biomechanics Results:
Indentation Stiffness [IRHI]
57.2 ±
10.9
Not significant
61.0 ±
10.2
7 Day 28 Day
Gene Expression in
Stored Allografts
Day 1
Day 21
4.5%
4.0%
3.5%
3.0%
2.5%
2.0%
1.5%
1.0%
0.5%
0.0%
Results:
GAG Content [% hexosamine/dry wt]
Not significant
Not significant
Not significant
4.2 ± 0.7 4.1± 1.3 4.0 ± 0.5 4.2 ± 0.5
1 Day 7 Day 14 Day 28 day
Gene Expression in
Stored Allografts
Microarray Technology Microarray Technology
• RNA �DNA, labeled
with fluorescent dyes, and
then washed over a glass
slide bearing a grid
spotted with DNA
sequences from known
genes.
140
120
100
80
60
40
20
0
Affymetrix
• By analyzing the location
and intensity of the
fluorescent signals, you
can determine the level of
activity for each gene
Affymetrix
Gene Array Results
Up Regulated Apoptosis Genes
Baseline
Day 21
Day 35
Casp6 Casp7 CD30 CD30L Fas FasL TNFa
Robertson, et al. CORR 2006
1/23/2012
4

Mechanism of Cell Death
Apoptosis Pathway
Storage Studies:
Conclusions
• Storage does not affect cartilage matrix or
biomechanical properties.
• Cell viability, y, cell density y and cell metabolism
decreased with increasing storage time.
• Optimum storage conditions not yet defined
– DMEM with FBS
• Euthermic storage vs. refrigerated
– Other potential anabolic/ anti-catabolic substances
• Anti TNF agents (Etanercept)
• In vivo studies are needed to define the
parameters of acceptable graft tissue quality.
Goat Allografts Stored in Media at 4°C
Role of Etanercept
Baseline With Etanercept Without Etanercept
4 Weeks
10%
Superficial
50% Middle
40% Deep
Future Allograft Innovations:
The Next 100 Years
• Changes in tissue banking paradigm
– universal donation, testing/ processing
• Storage or cryopreservation technology
• Molecular modulation of graft
– bone and cartilage growth factors
– Immunoreactivity
• Allografts as scaffolds for cell based technologies
– mature matrix
• Allograft cartilage as a cell source for tissue
engineered repair
• Joint fabrication
1/23/2012
5

Thank You
Summary
• Fresh grafts perform better than frozen
grafts
• Storage necessary for processing but
decreases chondrocyte viability
• If you use osteochondral allografts,
understand what happens before the graft
is delivered to your OR and after it is
implanted.
1/23/2012
6

Osteochondral Allograft: Clinical Experience
David R. McAllister, MD
Professor
Chief, Sports Medicine Service
Department of Orthopaedic Surgery
David Geffen School of Medicine at UCLA
Indications
• Focal articular cartilage lesions of the femoral condyles of the knee
• Large with full-thickness articular cartilage loss (with or without subchondral bone
loss-i.e. OCD)
• Failed previous articular cartilage treatment
Rationale
• Replacing damaged articular cartilage with size-matched LIVE articular cartilage
• Large single plug minimizes fibrocartilage formation (i.e. “grout”)
• Allograft source alleviates donor site morbidity concerns seen with autogenous
cartilage transplantation
• Only articular cartilage procedure which results in hyaline cartilage
Results
• Improved with good fit, unipolar surface, and young graft donor
• Survivorship:
5 years-95%
10 years-71%
20 years-66%
Shasha, et al: Cell and Tissue Banking, 2002
Results
• 73% G/E results after 10 years
• 76 % G/E, overall
• 84% G/E for unipolar lesions
• 50% G/E for bipolar lesions
Chu,et al, CORR, 1999
Factors Affecting Success
• Size
• Fit
• Match
• Alignment
• Fresh/Frozen

Drawbacks
• Can be difficult to obtain fresh non-irradiated grafts
• Risk of disease transmission and infection
• Logistically challenging
Osteochondral Allograft Transplantation
• Allografts are most effective when transplanted fresh. When kept in tissue culture
medium at 4°C, articular graft chondrocytes remain alive although viability decreases
with time.
• Avoid use of use fresh frozen grafts
ACT Instruments Overview
Lesion Gauge
• Sized to Cover entire Lesion
• Tripod Base
– 12, 4, and 8 o’clock Positions
– Best Stability on a Curved Surface
• Cannulated to Accept Guide Pin
• Color Coded Plastic
Guide Pin
• 2.4mm
• Drill Tip
• 30cm in Length
• Calibrated from 0mm to 50mm
– 1.0 cm Increments
– Read from the Proximal End of Lesion Gauge
Guide Pin
Lesion Reamer
• Dual-Cutting Surface
– Outer Edge
• Large Channels to Expel Debris
• Calibrated in 5mm Increments
• Cannulated
• Color Code Banding
Depth Gauge
• Cylinder – One per Size
• Calibrated Circumferentially in 1mm Increments
– Numbers Appear at 12, 4, & 8 O’Clock
• Use Skin Pen to Mark Three Spots
• Transfer Readings to Graft
• Stainless Steel
• Color Code Banding

GraftStation
• Holds Allograft for Graft Preparation
• Guide Arm Adjusts
• Insert Lesion Gauge
• Lock Arm
• Insert GraftMaker
• Create Graft
• Pads on Base Fine-Tune Depth and Chamfer Edges to Aid Insertion
GraftMaker
• Two-Piece Instrument
– Cutting Section
– Driving Section
• Creates Cartilage Graft (core)
• Windows in Cutting Section
– 5mm Increments
– Depth Reading
GraftMaker
• Cutting Section Detaches
– Push Graft Out w/o Touching Cartilage
• Cannulated
• Color Code Banding
Sizing Forceps
• Capture Graft Circumferentially
• Cartilage Not Touched
• Act as a Cutting Guide
– Final Depth Cut Made Here
• Ratchet Handle Clamps and Holds Position
Dilator
• Use to Dilate Graft Site, If Needed
• Optional Use to Push Graft Out of GraftMaker, If Using This Technique
• Color Code Banding
Tamp
• Plastic, High-Concave Cut-out
– Protects Cartilage
– Impacts Only on Edge
• Color-Coded Plastic
Retrieval Pin
• Threaded Tip
• 30cm Length
• Attach to Drill to Advance into Graft
• Pull Graft Out of Misaligned Position
• Reposition Graft

Mallet
• Used for Tamping and Dilating
• Slotted for Cannulated Option
• Special Fitting Acts as Wrench
• Used to Tighten GraftStation Clamp
– Wrench Also Included
Two Instrument Cases
• Common Instruments
– Guide Pins
– Retrieval Pin
– Hudson Adaptor
– Pusher Rod
– GraftStation
– Mallet
– Wrench
• Size-Specific Instruments
– Lesion Gauge
– Lesion Reamer
– GraftMaker
– Depth Gauge
– Sizing Forceps
– Dilator
– Tamp
• 12 Steps to OC Tx Success!
Step 1: Size Defect
Step 2: Place Guidepin
Step 3: Ream Lesion
Step 4: Size Lesion and Measure Depth
Step 5: Place donor in Workstation
Step 6: Cut Graft
Step 7: Make Crosscut
Step 8: Remove Graft
Step 9: Mark depth
Step 10: Cut to proper depth
Step 11: Place into defect
Step 12: Tamp into place

12 th International Sports Medicine Fellows Conference
January 27-29, 2012● Carlsbad, California
Session II
9:30 AM - 9:45 AM Autologous Chondrocyte Implantation from Bench to Present Jason Scopp, MD USA
9:45 AM - 10:15 AM
Complex Reconstruction and Osteotomy: Pre-Operative Planning
and Technique (Presentation via Live Video Stream)
Brian Cole, MD USA
10:15 AM - 10:30 AM Patellofemoral Joint Algorithm and Osteotomy to Arthroplasty Jack Farr, MD USA
10:30 AM - 10:45 AM Meniscus Allografts and Meniscal Implants Wayne Gersoff, MD USA
10:45 AM - 11:00 AM
Next Generation Experience BMAC Other Scaffolds: Europe and
Beyond
Alberto Gobbi, MD ITALY
11:00 AM - 11:15 AM Stem Cells: Fact or Fiction and Opportunity C. Thomas Vangsness, MD USA
11:15 AM - 11:30 AM Post Fellowship Award Presentation Christopher Kreulen, MD USA

Autologous Chondrocyte
Implantation
Jason M. Scopp, M.D.
Director, Joint Preservation Center
Peninsula Orthopaedic Associates, PA
Salisbury, Maryland
Functional Unit
The Macroenvironment
• Limb alignment
• Meniscus status
• Ligamentous status
• Cartilage status
• Any change in one factor can affect the
others via Chondral Overload Syndrome
Be a cartilage doctor
An intact surface is an important
thing
Decision Making
• Small lesions ≠ large lesions
• Articular cartilage defect ≠ osteoarthritis
2 Stage Technique
1/4/12
1

Indications
• Symptomatic ICRS Grade III and IV
lesions
• High demand patients age 15-55 with
motivation and potential for compliance
and realistic expectations
• Size >2cm² and < 12cm² (???)
• Continued pain after primary treatment
Arthroscopic Evaluation
• Manage concomitant
pathology
• Size defect
• Initiate primary
treatment
• Biopsy
• Policy
Insurance Policy
Autologous chondrocyte implantation for the treatment of cartilage
defects is considered medically necessary for patients with cartilage
defects of the femoral condyle (medial, lateral or trochlear) when the
case meets the criteria set forth in the Policy Guidelines.
• Patients for treatment with autologous chondrocyte implantation will
present with the following:
– a cartilage defect within a range of 1.5 cm to 3.0 cm in largest
diameter, and
– for whom more conservative treatment has failed, or is likely to fail
to relieve the symptoms.
– The Medical Director may consider patients with variations in
lesion size or location, or those patients with more than one lesion
No mention of ACI as secondary treatment option for this size
The Biopsy
Implant Day The Tools
• Superomedial or
superolateral trochlea
• Lateral intercondylar
notch
• 200-300 mg (2 tic
tacs)
• Cartilage and bone
• 200Kcells à� 12
million
1/4/12
2

Retractors Position
Exposure
• Consider concomitant procedures
• Epi soaked pledgettes
• Thrombin spray
• Gel foam
• Sponge
• Fibrin glue
• Needle-tip bovie
• NO tourniquet
Hemostasis
Defect Preparation
• Debride to normal
cartilage margins
• 15 blade and ring
curette
• Maintain calcified
cartilage layer
• Hemostasis
• Make template for
periosteum
Periosteum Harvest
• Oversize by 2 -3mm
• 3-5 fb below pes
– Thin to win
• Remove fascia and
fat with wet sponge or
fine scissors
– Be careful
• Femoral metaphysis
– Thicker--hypertrophy
– Adhesions (Seprafilm)
1/4/12
3

Don’t forget to mark Graft fixation
Tips for uncontained
• Anchors
– Mitek Microfix
• Drill keith needles
• OATS plug
• 6-O vicryl DYED
• 4 corners of compass
– Trochlea and patella
– Avoid manhole cover
• Leave open region to
implant
• Seal with fibrin glue
• Test for watertight
– epi
Sandwich Technique Lesions
>8mm Deep
Periosteal Replacement Post-op
• Nerve blocks à� Outpatient
• CPM 6-8 hours a day
• PWB 6-8 weeks
• Proliferation Phase: 0-6wà� Soft
• Transition Phase: 7w-6mà� Putty
• Remondeling Phase: 6m-36mà� Stiffens
1/4/12
4

Results
• ACI can be used for defects

Profiling the Optimal Patient
• Fewer surgeries

Brian J. Cole, MD, MBA Office: 312-243-4244 1
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Notes:
Cartilage Repair: Complex Reconstruction with Pre-Operative
Planning and Techniques
1) Presentation
a) Pain
b) Instability
c) Deformity
d) Varus/Lateral Thrust
e) Prior Meniscectomy
2) Treatment Goals
a) Reduced pain
b) Protect cartilage repair
c) Eliminate instability
d) Improve function
3) Cartilage Resurfacing
a) Patient Evaluation
i) Hx
ii) PE
iii) Ancillary Testing
(1) Rosenberg
(2) Long-leg alignment
(3) MRI
iv) Prior arthroscopic hx/records/photos
b) Decision Variables
i) Defect-Specific
(1) Location
(2) Size/Depth
(3) Geometry
(4) Containment
ii) Patient-Specific
(1) Age
(2) Demand-Match
(3) Response to prior tx
(4) Comorbidities
(a) OCD
(b) Alignment
(i) T-F
(ii) P-F
(c) Stability
(d) Meniscal Deficiency
c) General Rules

Brian J. Cole, MD, MBA Office: 312-243-4244 2
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Notes:
i) Avoid thinking linearly
ii) Repair when possible
iii) Re-establish subchondral bone
iv) Do not correct alignment with grafts
v) Avoid burning bridges to future treatment options
d) Options
i) Palliative
(1) Debridement/Lavage
ii) Reparative
(1) Microfracture
(2) Abrasion
(3) Drilling
iii) Restorative
(1) ACI
(2) OC Grafting
(a) Autografts
(b) Allografts

Brian J. Cole, MD, MBA Office: 312-243-4244 3
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Notes:
e) General Algorithm

Brian J. Cole, MD, MBA Office: 312-243-4244 4
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
4) Osteotomy
a) Osteotomy Goals (Mechanical Axis)
i) Pain/Arthrosis � Overcorrect (62% across plateau)
ii) Cartilage Restoration � Correct (50% across plateau minimum)
iii) Instability � Sagittal Slope Correction
Notes:
b) Opening Wedge Advantages
i) Avoid TF Joint/Peroneal Nerve
ii) Maintains Proximal Tibial Shape
iii) Avoids medial tibial displacement
iv) Reduced Infera (less complicated arthroplasty)
v) Intraoperative Correction
vi) Biplane Osteotomy (Sagittal/Coronal)
vii) Simplicity
viii) Lower Morbidity
(1) Single cut
(2) No anterolateral dissection
c) Disadvantages
i) Bone Graft
ii) Non-Union
iii) Large Corrections Difficult
d) Clinical Indications
i) Malalignment + Arthrosis
ii) Malalgnment + Instability
iii) Malalignment + Arthrosis + Instability
iv) Malalgnment + Cartilage Restoration (Meniscus/Articular)
e) Contraindications
i) Contralateral compartment arthrosis/prior lateral meniscectomy
ii) Motion loss (< 0-75 o )
iii) Inability to tolerate postoperative restrictions
iv) Joint subluxation
f) Patient Assessment
i) History/PE
ii) Operative Record Review
iii) Instability Assessment
iv) Short-Leg Cast/Brace Trial
(1) Gait-Analysis
g) Radiographic Assessment
i) Bilateral Standing Hip to Ankle
(1) Single-Leg Standing Hip to Ankle
h) Alignment Assessment
i) Tibiofemoral Angle (5-7 o Valgus): Single-Leg Standing Hip to Ankle

Brian J. Cole, MD, MBA Office: 312-243-4244 5
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Notes:
ii) Mechanical Axis (Neutral): Deviation of weight-bearing line (preferred)
iii) Sagittal Plane: Tibial Slope (1-10 o )
(1) Increased slope = Increased Anterior Translation = Worsens ACL = Helps PCL
(2) Decreased slope = Increases Posterior Translation = Helps ACL = Worsens ACL
i) Surgical Technique
i) Incision: Medial, 5 cm, start 1 cm below joint line extend to bottom of pes anserinus
(similar to ACL incision for tibial tunnel centered b/w TT and posteromedial tibia)
ii) Incise pes anserinus longitudinally and elevate and protect MCL
iii) Elevate superficial MCL
iv) Expose junction b/w fat pad and patellar tendon insertion
v) Right angle under patellar tendon
vi) Guide pin placement
(1) Fluoroscopy
(2) Perpendicular to tibia (coronal)
(3) Start just below beginning of TT (4 cm below joint line)
(4) Cross tibia obliquely at patellar tendon insertion
(5) End at proximal fibula head (1 cm below joint line)
(6) Place 2 nd pin more posterior/attach cutting guide
(7) Cut below guide under fluoroscopic guidance leave lateral 1 cm
(8) Finish with osteotomes
(9) Gradual opening
(10) Plate placement
(a) 2-6.5 mm cancellous screws proximally
(b) 2-4.5 mm cortical screws distally
(11) Bone Graft
(a) ICBG
(b) Cortical ring allograft
(c) DBM supplement
j) Pearls and Pitfalls
i) Expose patellar tendon insertion at tibial tubercle
ii) Flouroscopic guidance
iii) More horizontal cut for larger corrections to improve fixation stability
iv) Osteotomy parallel to sagittal slope joint line
v) Osteotomy below guide pin to avoid fx
vi) Thin flexible osteotomes
k) Rehabilitation
i) Hinged knee brace
ii) Immediate ROM
iii) NWB/HTWB 4-6 Weeks
iv) Gradual WB at 5-6 Weeks (Radiographic healing??)
v) CPM with intraarticular work
vi) 6-12 weeks: functional program strengthening
vii) > 12 weeks: muscular endurance
l) Complications
i) Intraoperative
(1) Fracture

Brian J. Cole, MD, MBA Office: 312-243-4244 6
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Notes:
(2) Intraarticular screw
(3) Medial cortex violation
ii) Early Postoperative
(1) Hematoma
(2) Compartment syndrome
iii) Late Postoperative
(1) Delayed union
(2) Non union
(3) Hardware failure
m) Special Situations
i) ACL & Varus
(a) ACL Alone (Shelbourne)
(b) HTO Alone
(i) Pain
(ii) Open wedge posteriorly (decrease slope)
(c) ACL & HTO
(i) Pain & Instability
(ii) Order
1. Intra-articular preparation
2. Shorter tibial tunnel
3. Femoral tunnel
4. Osteotomy (oblique and start low)
5. Fix osteotomy
6. Pass graft
7. Recess femoral plug to handle graft mismatch
8. Cut tibial plug after fixation
(2) PCL & Varus
(a) Opening wedge anterior (increased tibial slope)
(3) Meniscus Transplant
(a) Young: combine
(b) Old: Osteotomy first, then transplant prn
(4) Articular Cartilage
(a) Young: combine
(b) Old: Osteotomy first, then transplant prn
5) Ligament Reconstruction
a) Cartilage Resurfacing: ACL Always reconstruct
i) Revision common
ii) Avoid tunnel communication (meniscus transplantation)
iii) Bone graft tunnel enlargement first and return
iv) Timing
(1) ACL & Meniscus transplant : Simultaneous
(2) ACL & Malalignment & Cartilage
(a) ACL first
(b) Alighment and Cartilage Resurfacing
(c) May try osteotomy first and then return prn
(d) May try ligament first and then return prn

Brian J. Cole, MD, MBA Office: 312-243-4244 7
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Questions
1. When performing marrow stimulation of the femoral condyle, it is important to:
A. Create vertical walls at the transition zone
B. Violate the calcified layer
C. Initially protect the defect from weigthbearing
D. Implement immediate post operative range of motion
E. All of the above
2. All of the following are true regarding osteochondral allograft transplantation except:
A. The graft should be initially maintained at 37 o C for no more than 28 days
B. A minimal amount of subchondral bone should be transplanted with the graft
C. It is acceptable to utilize a contralateral femoral condyle for a donor graft
D. The graft should be gently impacted
E. Bipolar grafts are associated with a guarded prognosis
3. Classic indications for autologous chondrocyte implantation assume all of the
following except:
A. The defect is associated with a minimal amount of bone loss
B. The defect must be contained
C. Sclerotic areas can be debrided even if bleeding occurs
D. Patellar alignment can be corrected simultaneously or in a staged fashion when
treating trochlear defects
E. A meniscus deficient knee should undergo allograft meniscus transplantation at
the same time the femoral condyle is treated.
4. In a patient with ACL deficiency who is in varus, a high tibial osteotomy can help by:
A. Increasing the posterior slope of the tibia in the sagital plane
B. Decreasing the posterior slope of the tibia in the sagital plane
C. Increasing contact pressures in the lateral compartment
D. Protecting an ACL reconstruction by reducing stress on the ligament
E. Both A and D
Answers
Question 1: E, All of the above
Question 2: B, The graft should be initially maintained at 37 o C for no more than 28 days
Question 3: B, The defect must be contained
Question 4: E, Decreases the posterior slope of the tibia and protects the ACL reconstruction
Notes:

Brian J. Cole, MD, MBA Office: 312-243-4244 8
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
CPT Codes
Meniscus Transplant 29868
Microfracture 29879
Osteochondral Allograft 27415
Osteochondral Autograft 29866
HTO 27457
DFO 27450
Notes:

Brian J. Cole, MD, MBA Office: 312-243-4244 9
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
REFERENCES
Cartilage Restoration
Garretson RB, Katolik LI, Bach BR, Verma N, Cole BJ: Dynamic contact pressure in the
patellofemoral joint. In Press: Am J Sports Med, 2004
Cole BJ, Lee SJ: Complex knee reconstruction: Articular cartilage treatment options.
Arthroscopy, (19) Supplement 1, 1-10, 2003.
Freedman K, Nho S, Cole B: Marrow stimulating techniques to augment meniscus repair,
Arthroscopy, 19(7):794-798, 2003.
Fox JA, Kalsi RS, Cole BJ. Update on Articular Cartilage Restoration, Tech in Knee Surg
2(1):2-17, 2003.
Farr J, Meneghini RM, Cole BJ: Allograft interference screw fixation in meniscus transplantation.
Arthroscopy, In press, March, 2004.
Cole BJ, Rodeo S, Carter T: Allograft Meniscus Transplantation: Indications, Techniques,
Results, J Bone Joint Surg, 84A:1236-1250, 2002.
Fox J, Cole BJ. Management of Articular Cartilage Injuries. Orthopedic Knowledge Update in
Sports Medicine, Volume #3, American Academy of Orthopedic Surgeons, 2003.
Cole BJ, Fox JA, Lee SJ, Farr, J. Bone bridge in slot technique for meniscal transplantation. Op
Tech Sports Med, 11:2, 144-155, April, 2003.
Fox JA, Lee SJ, Cole BJ. Bone plug technique for meniscal transplantation. Op Tech Sports
Med, 11:2, 161-169, April, 2003.
Farr J, Cole BJ: Meniscus transplantation: Bone Bridge in slot technique. Op Tech Sports Med,
10(3):150-156, 2002.
Fox JA, Freedman KB, Lee SJ, Cole BJ. Fresh osteochondral allograft transplantation for
articular cartilage defects. Op Tech Sports Med, 10(3): 168-173, 2002.
Freedman JB, Coleman SH, Olenac C, Cole BJ: The biology of articular cartilage injury and the
microfracture technique for the treatment of articular cartilage lesions. Seminar in Arthroplasty,
13(3): 202-209, 2002.
D’Amato M, Cole BJ: Autologous Chondrocyte Implantation, Orthopedic Techniques, 11:115-
131, 2001.
Cole BJ, Farr J: Putting it all together, Orthopedic Techniques, 11:151-154, 2001.
Miller M, Cole BJ: Atlas on chondral injury, Orthopedic Techniques, 11:145-150:2001.
Notes:

Brian J. Cole, MD, MBA Office: 312-243-4244 10
Section Head, Rush Cartilage Restoration Center` Fax: 312-942-1517
Section of Sports Medicine EM: bcole@rushortho.com
Rush University Medical Center
Chicago, IL
Website: WWW.cartilagedoc.org
Cole BJ, DiMasi M: Single-stage autologous chondrocyte implantation and lateral meniscus
allograft reconstruction. Orthoped Tech Rev. 2:3, 44-59, 2000.
Cole BJ (Section Ed.): Cartilage Restoration: Alternative techniques for the management of
articular cartilage disease. In: The Arthritic Knee, Rosenberg, A.G., Mabrey, J.D., and Woolson,
S.T. (Eds.). Rosemont, Illinois, American Academy of Orthopaedic Surgeons, 2000.
Osteotomy
Brown G, Amendola A: Radiographic evaluation and pre-operative planning for high tibial
osteotomy. Op Tech Sports Med, 8:1, January 2000.
Cole BJ, Freedman KB, Takasali S, Hingtgen B, DiMasi M, Bach Jr. BR, Hurwitz DE: Use of a
lateral offset short-leg walking cast before high tibial osteotomy. Clin Ortho Rel Res, 408:209-
217, 2003.
Puddu G, Cipolla M, Franco V. A plate for open wedge tibial and femoral osteotomies.
Presented at The Congress of the International Society of Arthroscopy, Knee Surgery and
Orthopaedic Sports Medicine; 1999; Washington, DC.
Hernigou P, Medevill D, Debeyre J, et al. Proximal tibial osteotomy with varus deformity: a ten- to
thirteen-year follow-up study. J Bone Joint Surg Am, 69:332, 1987.
Koshino T, Murase T, Saito T. Medial Opening-Wedge High Tibial Osteotomy with Use of Porous
Hydroxyapatite to Treat Medial Compartment Osteoarthritis of the Knee. J Bone and Joint Surg
Am, 85:78-85, January 2003.
Koshino T, Morii T, Wada J, et al. High Tibial Osteotomy with Fixation by a Blade Plate for
Medial Compartment Osteoarthritis of the Knee. Orthopedic Clinics of North America, 20:227-
243, April 1989.
Notes:

12 th Annual International Sports Medicine Fellows Conference
Patellofemoral Joint Algorithm and Osteotomy to Arthroplasty
January 28, 2012 10:15-10:30am
Jack Farr, M.D.
OrthoIndy Knee Care Institute
1260 Innovation Parkway #100
Greenwood, IN 46143
Ph: 317-884-5200
Fax: 317-884-5365
E-mail: indyknee@hotmail.com
Patellofemoral Compartment: AMZ and PFA
Osteotomy Planning
1. Step One: Define the Pathology
a. Classifications to aid in Treatment
i. Morphology
ii. Traumatic vs. Atraumatic (Primary DJD)
iii. Fulkerson Alignment Classification
1. Fulkerson Alignment Classification: Alignment & TT-TG
a. Correlate Patellar position with contribution of TT-TG
b. Mean of Asymptomatic patients: 13 mm
c. Outlier symptomatic group: >20 mm
iv. Regional Chondrosis Mapping
1. Normalization of PF stress without Cartilage Restoration: AMZ
(Pidoriano and Fulkerson, 1997)
a. Inferior Pole and Lateral Facet: 87% G/E
b. Medial Facet: 55% G/E
c. Proximal Pole and Diffuse: 20% GE
d. Concomitant Central Trochlear Involvement: All Poor
v. Soft Tissue Envelope
1. Medial Patellofemoral Ligament Status
2. Lateral Retinaculum Status
2. Step Two: Identify Why There Is Pain
a. Chondrosis ≠ pain
Diagnosis of Exclusion
i. Articular cartilage is aneural
ii. Pain therefore originates from:
1. Soft tissue (Synovium, Capsule, Tendons and Ligaments)
2. Nerves (Local or Remote, e.g., saphenous, neuroma)
3. Bone (Local or Remote, subchondral, referred hip)
4. Need to identify those patients with pain on the basis of the
mechanically identifiable factors and associated chondral defects;

exclude CRPS and dehabilitation (exceeding Dye Envelope of
Function)
3. Step Three: Right Surgery for the Right Patient - Patient Specific Demand Matching
a. Treat both Mechanical and Chondral Pathologies
4. Step Four: Applying the Specific Surgery
a. Tibial Tuberosity Medialization
i. TT-TG distance > 20mm
ii. If suspected Femoral/Tibial rotational abnormalities (e.g., Increased
femoral anteversion): CT assess hip/knee/ankle rotation (Teitge)
b. Deciding on Tuberosity Transfer
i. Degree of Anterization:
1. Ferrandez 10 mm Clin Ortho 1989
2. Ferguson 12.5 JBJS 1979
3. Fulkerson 15 mm AJSM 1990
ii. Medialization
1. Do NOT over-medialize—Andrish 2005
2. Goal to normalize in range of TT-TG 10-15 mm
iii. FEA Patient-Specific Models for Tuberosity Transfer: AMZ
20% mean decrease in stress
c. Planning Tuberosity Transfer
i. Preop Planning: Knee Specific
ii. Steepest slope approx. 60 degrees
iii. Applying Trigonometry to a constant elevation of 15mm:
1. 60 degree slope & elevation 15 = 8.7 mm medialization
2. 50 degree slope & elevation 15 = 12.5 mm medialization
3. 45 degree slope & elevation 15 = 15 mm medialization
4. Example of Typical Excessive TT-TG of 25 treated with
a. 60 degree slope or 8.7 = 16.3 post op TT-TG
b. 50 degree slope or 12.5 = 12.5 post op TT-TG
d. AMZ-Indications
i. TT-TG - abnormally elevated and distal lateral chondrosis of the patella
without trochlear involvement
ii. Very steep AMZ in severe lateral PF compartment overload (excessive
lateral compression/ tilt)
iii. Straight anterization when TT-TG is within normal limits and the goal is
to decrease PF forces (Fulkerson osteotomy modified for straight
anterization).
e. AMZ-Contraindications
i. Proximal pole, medial, panpatellar chondrosis or concomitant chondrosis
of the trochlea
ii. TT-TG within normal limits (Straight anterization is an option in this
setting)
iii. Pain is not directly related to a biomechanical abnormality that will be
reversed by
f. TTO-Indications
i. Highly controversial

ii. Lyon France school of thought: Patellar alta and trochlear dysplasia are
the main problems to be addressed for patellar instability
1. Distalization of the tuberosity only
iii. US surgeons are divided: patellar instability is treated with good reported
results by:
1. TTO alone (medialization +/- distalization)
2. MPFL repair/ reconstruction alone
3. MPFL surgery concomitant with TTO
iv. TTO biomechanically indicated
1. Normalization of the lateral resultant vector would appear to aid in
the PF management when there is minimal chondrosis (grade 2 or

AMZ
Author Procedure Journal Subjects Follow up Results
Fulkerson
JP (11)
Pidoriano
AJ (5)
Buuck D
(12)
Bellemans
J (13)
Naranja
RJ (14)
AMZ AJSM 1990 30 pts12
pts
AMZ AJSM
1997
AMZ Op Tech Spt
Med
> 2 y F/U>5 y
F/U
89-93% G/E
Advance DJD
subgroup: No E;
75% G
23 pts 10 F/U 87% G/E
distal/lateral
chondrosis
55% G/E medial
chondrosis
poor results with
trochlear
42 knees
in 36 pts
AMZ AJSM 1997 29
patients
Elmslie-Trillat
Maquet
AJSM 1996 55 knees
in 51
patients
chondrosis
8.2 mean F/U 86% G/E
32 mon mean
(25- 44 mon)
74.2 mon (13
– 196 mon)
28 successful
73-84% G/E

PFA
Authors Procedure Journal Subjects Follow up Results
Sisto DJ,
Sarin VK
(15)
Ackroyd
CE, et.al.
(16)
Merchant,
AC (17)
Lonner,
JH (18)
Kooijman
HJ, et.al.
(19)
Custom PFA
(Kinamatch,
Kinamed)
Avon
(Stryker)
LCS based
(DePuy)
Lubinus
(Waldemar
Link) and
Avon
(Stryker)
Richards
(Smith
Nephew)
JBJS
2007
JBJS
2007
CORR
2005
CORR
2004
JBJS
2003
25 PFA
in 22
pts.
109
PFA in
85 pts.
16 PFA
in 16
pts
30 PFA
Lubinus 25
PFA
Avon
56 PFA
in 51
pts.
73m
mean
range; 32 to
119 months
Min 5
yr F/U
F/U
2.75-
6.25
years
4 yr
mean
(2-6) 6
mon
mean
(1-12
mon)
17 y
mean
range
15-21
25/25 G/E
80% success
95.8%
survival
94% G/E
84% G/E
96% G/E
86% G/E
2% loosening

Meniscal Allograft Transplantation
12 th Annual Articular Cartilage Course
Wayne K. Gersoff, M.D.
1. Goal of MAT is to preserve articular cartilage, inhibit
degeneration, and prolong function.
2. Historical Perspective- first MAT done in 1984, since
then thousands have been performed.
3. Basic Science Considerations
Chondroprotective Potential
Healing Potential
Immunoligoc Factors
Histological Analysis
Preservation Techniques
Biomechanical Considerations
4.Tissue Preservation
Fresh- logistically not practical
Freeze Dried – cell death, structural damage
Cryopreservation – cost, allow for slight increase in cell
viability.
Fresh Frozen – slight increase in cell death, minimal
structural damage.
Role of cell viability – limited, meniscus acts as a
biological scaffold.

5. Tissue Preservation
Gamma radiation negative effects- Naal, J. Biomed
Mater. 2008.
Sterilization doesn’t compromise tissue integrity –
McNickle, COOR.2008.
Significant deep freezing can alter meniscus collagen
Gelber. Knee Surg Sports Trauma. 2008.
Proprietary processing techniques
6. Indications : subtotal or total menisectomy; pain secondary to
meniscal deficiency; grade 3 or less chondromalacia; stable
knee without malalignment.
7. Contraindications : RA, Metabolic degenerative disease,
obesity
post-infectious disease, remodeling of femoral condyle.
8. Techniques
Double bone plug
Bone bridge – slot and trough
9. Double Bone Plug
commonly used on medialside
importance of anatomical placement of both horns
maintain configuration
avoids tibial spine debridement
fragility of bone plugs and fixation
10. Bone Bridge
utilized medially or laterally
allow for maintenance of anatomy and architecture

provides excellent bone fixation and healing
Trough – press fit fixation
Slot – interference screw fixation
11. Sizing Considerations
AP and lateral radiograph with radiologic marker – Pollard
Width – tibial eminence to periphery of tibial compartment on
AP radiograph
Accuracy of predictability – McDermott, 2004
MRI of contralateral knee – Prodromos. Arthroscopy. 2007
12.Complications
Arthrofibrosis
Meniscal Detachment
Meniscal Shrinkage
Meniscal Failure
Meniscal Extrusion
13. Pitfalls and Pearls
Appropriate surgical planning
Don’t compromise exposure
Adequate fixation techniques
Presence of meniscal remnant
Accurate positioning of bone
Anterior horn fixation
Placement of pull through suture
14. Rehabilitation
Early protected WB, Full WB at 4-6 weeks
Limited early motion
Similar to delayed meniscal repair

Use of Unloader brace
Early treatment of concerns
15.Concomitant Procedures
Ligamentous Reconstruction
Malalignment Correction
Articular Cartilage Restoration
16. Asymptomatic Post-Menisectomy Knee
Education about signs and symptoms of knee degeneration
45 degree PA radiographs
? yearly bone scans
Articular cartilage tends to rapidly break down, especially in
lateral compartment.
Younger patient- strongly consider early intervention
17. Future Considerations
Tissue Scaffolding
Tissue Engineering
Synthetic Replacements
Allograft – immunologic and technical considerations
Long Term Functional Results
18. Treatment of Meniscal Deficiency and Chondral Defects
19. Symbiotic Realtionship of Meniscus and Articular
Cartilage
Concept of Functional Unit

20.Common Factors in Treatment
Knee Stability
Knee Alignment
Knee Environment
21. MAT and ACI
arthroscopic debridement
arthrotomy and preparation of tibial bone anchor site
meniscal allograft and chondral defect preparation
placement and fixation of meniscal allograft
completion of ACI procedure
22. Applications for 2012
Complex injuries to meniscus will continue and be problematic
Articular cartilage injuries present challenge for athletic
population especially competitive athletes.
Primary goal is not return to competitive sports but restoration
of functional knee.
Challenging population is the adolescent and young adult.

BASIC SCIENCE
NEXT GENERATION EXPERIENCE BMAC & OTHER SCAFFOLDS:
EUROPE AND BEYOND.
Alberto Gobbi,MD, Anup Kumar,MD, GeorgiosKarnatzikos, MD.
Relevant Anatomy
Articular cartilage is a thin layer of specialized connective tissue lining the articulations of
diarthrodial joints. Properties, which are unique to this tissue, enable an almost frictionless joint movement
and afford protection to the underlying bone from excessive load and trauma by dissipating the forces
produced during movement.
The structural organization of articular cartilage can be divided into four major zones: superficial,
middle, deep and calcified [45, 69]. Each zone is distinctly structured with cells and extracellular matrix
(ECM) organized in specific patterns. The cells, known as chondrocytes, make up 1-2% of the total weight
of the articular cartilage. On the other hand, the ECM, which makes up the rest of the cartilage, is generally
composed of type II collagen and proteoglycans.
Biomechanics
Within joints and in particular the knee, there are two types of cartilage: fibrocartilage and hyaline
cartilage. Fibrocartilage is an elastic or “fibrous” cartilage of which the menisci are composed whereas
hyaline cartilage is the tissue that covers the extremities of the bones that make up the joint. Hyaline cartilage
has an extremely important biomechanical function as shock absorber as well as providing frictionless
movement to the joint. Even though this layer of cartilage is only a few millimetres thick it has a significant
capacity to absorb forces as well as distributing load to reduce stress on subchondral bone.
Once this protective layer of articular cartilage is compromised, subsequent trauma and excessive
loading can accelerate the progression of the “wear and tear”. Moreover, significant functional properties are
lost leading to further pathological changes that can involve the surrounding cartilage and subchondral bone
[66, 69].
1

Biology
As early as 1743, Hunter recognized that “articular cartilage lesions don’t heal”; the limited intrinsic
healing potential of articular cartilage is attributed to the presence of few and specialized cells with a low
mitotic activity [38]. As the human body matures, the cell density, which influences the amount of
extracellular matrix produced, declines further, limiting its capacity to regenerate. The reparative capacity of
cartilage is further reduced by the fact that the cartilage is avascular. The absence of a vascular network
prevents access for mesenchymal stem cells and macrophages, which would normally help repairing tissues.
Stem cells are responsible for the formation of new chondrocytes while macrophages remove debris
associated with damaged cartilage. As a result, once injury occurs, surgical intervention may be necessary to
achieve repair of the resulting focal chondral defects to obtain a good functional outcome.
CLINICAL EVALUATION
History
Patients suffering from chondral injuries often find it difficult to recall a specific incident that
triggered their symptoms. Swelling is usually present in the affected knee, which can sometimes be
accompanied by mechanical symptoms like catching and clicking. A high index of suspicion for chondral
injuries should be considered in patients who present with episodes of recurrent swelling in a knee that has
effusion at the time of examination [52]. In addition, Mandelbaum emphasized that chondropenia (a process
of loss of cartilage volume and elevation of contact pressures over time resulting in downward progression
on the dose response curve and the eventual OA formation) as a possible causative factor, should not be
overlooked when evaluating patients who present with these particular knee symptoms [46].
Physical Findings
Several authors have reported specific symptoms synonymous to chondral defects. Brittberg et al
and Ochi et al [10, 11, 61] stressed that knee pain, symptoms of locking, retropatellar crepitus and swelling
are among the prominent findings to look out for. Other authors including Hangody et al [34, 35] mentioned
that instability could also be present. As signs and symptoms elicited during physical examination can mimic
the presentation of other knee pathologies, authors agree that correlation with other diagnostic modalities
should be made routinely to increase the accuracy of diagnosis.
2

Imaging
Among the diagnostic imaging modalities used, MRI has proven to be the most accurate having a
sensitivity which is > 95% [14, 36, 37]. Aside from delineating the extent of the articular cartilage lesions,
subchondral bone and associated ligament or meniscal injuries can also be assessed. The use of fast-spin-
echo (with or without fat suppression) and/or fat-suppressed (or water-selective excitation) spoiled gradient-
echo image for better resolution has been recommended. Signal properties of articular cartilage are
dependent on: MR pulse sequence utilized, cellular composition of collagen, proteoglycans and water,
orientation of collagen in different laminae of cartilage, and effective cartilage pulse sequencing (Potter et al)
[70].
Recently, surgeons used arthroscopy more extensively as a diagnostic tool: the benefit afforded by
direct visualization of the extent of the defect, together with the information provided by MRI significantly
enhances the surgeon’s capacity to precisely plan the appropriate treatment necessary to address the
pathology.
Decision Making, Algorithms and Classification
The Outerbridge classification was the traditional system used but recently a more comprehensive
system (ICRS Classification) has been adopted [10].
Several options exist in the treatment of cartilage lesions; however, integrating all of these into a
comprehensive algorithm has not been easy. Any form of planned treatment should be based on patient
characteristics and expectations, clinical symptoms and type of lesions.
One algorithm proposed by Cole and Miller [17, 51] presents an overview of a surgical-decision
scheme where multiple options are presented for similar lesions without endorsing a specific treatment over
the others.
In general, surgeons agree that parameters such as lesion size, depth and associated issues,
like alignment, ligament and meniscal integrity should be considered when planning treatment for
chondral defects. Furthermore, other factors related to the patient (e.g. age, genetic predisposition,
level of activity, associated pathologies and expectations) should not be overlooked.
3

TREATMENT
Operative
Traditional palliative techniques or newer reparative treatment options have demonstrated variable
results. Lavage and chondroplasty can provide symptomatic pain relief with no actual hyaline tissue
formation. However, these techniques remove superficial cartilage layers, which include collagen fibers that
are responsible for the tensile strength, creating a less functional cartilage tissue [49]. Bone marrow
stimulation techniques, such as subchondral plate drilling or microfracture have been reported to stimulate
production of hyaline-like tissue with variable properties and durability compared to normal cartilage, but it
has been observed in many cases that these techniques tend to produce fibrocartilaginous tissue, which
degenerates with time [29, 31, 53, 73]. Osteochondral autologous transplantation and mosaicplasty can
restore normal cartilage tissue, but they can be applied only to small defects and there are some concerns
regarding donor site morbidity [29, 34]. Autologous chondrocyte implantation, which was first introduced
by Peterson, on the other hand, has been proven to be capable of restoring normal hyaline-like cartilage
tissue, that is mechanically and functionally stable even in athletes at long-term follow up, but this method
showed local morbidity for periosteal harvest and requires two surgical procedures [6, 36, 37, 54, 68].
The apparent complexity of the Peterson periosteal technique and the possible complication of
periosteal patch hypertrophy prompted surgeons to look for alternative techniques to enhance cell delivery
and outcome. At present the most promising technique seems to be tissue engineering, where cells are
combined with scaffolds to pre-form a given tissue. In general, the concept involves cultured autogenous or
allogenous chondrocytes integrated in biodegradable and biocompatible scaffolds. Once cultivated on the
scaffold, the chondrocytes must reacquire and maintain their chondrogenic phenotype in order to synthesize
an extracellular matrix containing type II collagen, glycosaminoglycans and proteoglycans, all of which are
necessary to produce hyaline cartilage.
Scaffolds
The use of a three-dimensional scaffold for autologous chondrocyte culture was developed with the
aim to improve both the biological performance of chondrogenic autologous cells as well as renders the
surgical technique easier, avoiding the use of the periosteal flap [30, 47, 48, 58]. A scaffold that is properly
sized can be positioned directly into the articular defect under arthroscopic guidance; although, some
4

technical limitations prevail, which include treating patellar lesions and posterior portions of femoral
condyles or tibial plateau and could partly be resolved with the development of new arthroscopic tools.
For some years now, different types of scaffolds with different matrices have been tested in animal
models, and in some cases, human trials were carried out to determine the efficacy in facilitating and
promoting cartilage repair. These scaffolds can be divided according to their chemical nature into protein
based polymers (collagen, fibrin and gelatine), carbohydrate polymers (hyaluronan, agarose, polylactic acid,
polyglycolic acid, chitosan and alginate) and other polymers (Teflon, Dacron, carbon fibers, polybutyric
acid, hydroxyapatite). Combinations of these different polymers are also available.
The ideal scaffold should be biocompatible (by not triggering any inflammatory response and not
being cytotoxic), biodegradable by offering a temporary support to cells in order to promote replacement of a
newly synthesized matrix and possibly induce proliferation of the transplanted cells. The matrix should also
be permeable to nutrients and provide firm adhesion to the surrounding cartilage wound edges so, as to
promote integration. Furthermore the scaffold must be reproducible and readily available and versatile for
repair and resurfacing [39].
Hyaluronan (hyaluronic acid, HA) is a naturally occurring and highly conserved
glycosaminoglycans, which is widely distributed in the body. It has proven to be an ideal molecule for tissue
engineering strategies in cartilage repair, given its impressive multi-functional activity through its structural
and biological role [16].
Through the chemical modification of HA, a scaffold can be obtained and may be processed into
stable configurations to produce a variety of biodegradable structures with different physical forms and in-
vivo residence times. Extensive biocompatibility studies have demonstrated the safety of these biomaterials
and their ability to be resorbed in the absence of an inflammatory response [15].
Three-dimensional non-woven scaffolds support the in vitro growth of highly viable chondrocytes
and promote the expression of the original chondrogenic phenotype [12, 13].
Chondrocytes, previously expanded on plastic and seeded into the scaffold produce a characteristic
extracellular matrix rich in proteoglycans and express typical markers of hyaline cartilage, such as collagen
II and aggrecan [1, 32, 55]. When implanted in full-thickness defects of the femoral condyle in rabbits,
chondrocytes regenerated a cartilage-like tissue [32, 33, 75].
5

An important issue to be addressed for the future perspective for cartilage repair is the quality of the
bonding and the integration of the newly formed tissue to the native tissue. Different studies were completed
and all seem to demonstrate the importance to the presence of both cells and the newly synthesized matrix
for achieving a stable healing [65].
Indications
The main indications for cartilage transplantation are symptomatic focal, full thickness cartilage
lesion (ICRS Grade III – IV) in the absence of significant arthritis in physiologically young patients (15 - 55
years). Additional factors to consider include the patient’s motivation and willingness to comply with the
post-implantation rehabilitation regimen. Defect size ranging from 2-12 cm 2 has been shown to be
favourable to regeneration. Osteochondritis Dissecans is not a contraindication for cartilage transplantation
as long as the bone loss does not exceed 8 mm [67].
Second Generation Autologous Chondrocyte Implantation Technique
Autologous Chondrocyte Implantation is carried out through the conventional arthrotomy approach;
however, recent advances in scaffold technology have enabled surgeons to perform this technique in
condylar lesions arthroscopically [2, 3, 26, 27, 42, 43, 48, 58, 74, 77].
The chondrocytes obtained from the biopsy taken during initial arthroscopy are then expanded in
vitro and finally seeded onto a 3-dimensional biomaterial where they will continue to proliferate and re-
differentiate. After proliferation, chondrocytes organize three-dimensionally to stimulate the synthesis of
extracellular matrix molecules and to prevent the loss of cell phenotype. The time frame observed for this
cultivation with respect to ACI is three to four weeks. At the time of graft implantation, the lesion is prepared
using a low-profile cannulated drill maintained in place by a Kirschner guide wire (0.9 mm diameter)
anchored in the bone. A depth of 2 mm is observed while preparing the defect to avoid violating the
subchondral bone plate. Once the defect is completely devoid of fibrotic tissues, the hyaluronic acid patch
containing the cultured chondrocytes is obtained. At this point, the knee joint is then drained of fluid and the
scaffold is loaded in the delivery system instrument using the cannula to position the patch into the defect.
The intrinsic adhesive characteristics of the scaffold assure its stability once positioned in the defect and in
the majority of cases there is no need for further fixation. Graft stability is then verified through a range of
6

knee movement prior to closure of the portals. Otherwise, in large uncontained defects and in the
patellofemoral compartment treated with open surgery, fibrin glue and/or other fixation systems maybe
indicated to keep the graft in place [28].
Several reports from controlled trials in patients operated with the use of these HA scaffolds have
been presented [48, 58]. However, the largest collection of data (more than 4.000 cases in Europe) using the
HA scaffold in clinical practice is represented by a multicenter observational study conducted in Italian
Orthopaedic Centers since 2001 [48, 63, 64].
EVALUATION OF OUTCOME
Since 2001, we have participated in an ongoing observational multicenter investigation to evaluate
the long- term clinical outcomes of the treatment with HA scaffold (HYAFF 11 ® Fidia Advanced
Biopolymers, Abano Terme, Italy).
141 patients with follow up assessments ranging from 2 to 5 years (average follow up time: 38
months) were evaluated. At follow up 91.5% of patients improved according to the international knee
documentation committee subjective evaluation; 76% and 88% of the patients had no pain and mobility
problems respectively assessed by the Euro Qol-EQ5D measure. Furthermore, 95.7% of the patients had
their treated knee normal or nearly normal as assessed by the surgeon; cartilage repair was graded
arthroscopically as normal or nearly normal in 96.4% of the scored knees; the majority of the second – look
biopsies of the grafted site, histologically, were assessed as hyaline-like. A very limited complication rate
was recorded in this study [47].
We also evaluated the patellofemoral full- thickness chondral defects treated with Hyalograft C.
Thirty-two chondral lesions located in the patella and trochlea, were treated. The International Cartilage
Repair Society-International Knee Documentation Committee and EuroQol EQ-5D scores demonstrated a
statistically significant improvement (P < .0001). Objective preoperative data improved from 6/32 (18.8%)
with International Knee Documentation Committee A or B to 29/32 (90.7%) at 24 months after
transplantation. Mean subjective scores improved from 43.2 points preoperatively to 73.6 points 24 months
after implantation. Magnetic resonance imaging studies at 24 months revealed 71% to have an almost normal
cartilage with positive correlation with clinical outcomes. Second-look arthroscopies in 6 cases revealed the
repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance [30].
7

COMPLICATIONS AND SPECIAL CONSIDERATIONS
The most commonly cited complications of first generation autologous chondrocyte implantation are
graft hypertrophy and arthrofibrosis [8, 42, 46, 54, 66]. Graft hypertrophy has been noted to occur between 3
to 9 months post-operatively and it is thought to result from abrasion of the periosteal patch, which
overhangs from the margin of the defect.
Adverse events of second generation ACI are apparently lower than first generation as reported by
Mandelbaum et al [46] and today second generation ACI represents a modern and viable technique for
cartilage full thickness chondral lesion repair but it is still not without problems: aside from the risk of
harvest site morbidity and two surgical procedures, the total cost of the operation, scaffold and process of
chondrocytes culture remain drawbacks of this procedures [6, 26].
IMPROVEMENTS
Very promising results have been shown with ACI to date, however, ACI is a technology that
involves the implantation of an expanded chondrocyte population derived from a cartilage biopsy. These
expansion results in the loss of its phenotypic traits also called “de-differentiation” [9, 44, 57, 79]. This
produces chondrocytes with a decreased capacity to regenerate hyaline cartilage cells [73].
Characterized Chondrocyte Implantation (CCI) is a second-generation ACI procedure that uses
ChondroCelect. ChondroCelect (Ti-Genix NV, Haasrode, Belgium) was developed to limit this loss of
phenotype and is an expanded population of chondrocyte that expresses a marker profile predictive of the
capacity to form stable hyaline like cartilage in vivo in a consistent and reproducible manner.
The chondrogenic character of the cells is confirmed with the ChondroCelect Score (CC Score)
representing a potency assay done after every step of the process. In a mouse model, the CC-score and
histological score showed a high degree of correlation. The CC-score is a range from -6 to +6 (4 positive
and 2 negative genetic markers). Only chondrocytes with a CC-score of > 0 would be used ensuring a high
cartilage-forming capacity.
In a prospective, randomized controlled trial, that compared CCI versus Microfracture as treatment
for single symptomatic cartilage defects of the femoral condyle, CCI produced a superior type of tissue
regenerate. The primary aims of the trial were (a) to demonstrate superiority of CCI over microfracture in
overall quality of structural regeneration of the articular tissue at 12 months post treatment using
8

histomorphometry and Overall Histology Assessment Score; and (b) to demonstrate a clinical outcome as
assessed by Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 months post treatment
that was at least comparable in both treatment groups. For the first time this trial proved that joint surface
repair/regeneration using cell technology produced higher quality regenerate than intrinsic repair. It also
showed clinical outcome similar in both treatments. These results suggest CCI may lead to an improved
long-term clinical outcome [73].
FUTURE DIRECTIONS
In the future the use of autologous mesenchymal stem cells seeded in a temporary scaffold with
growth factors could be an improvement of the currently available techniques.
Mesenchymal Stem Cell
ACI has the potential for repair of the damaged cartilage and, as of today, remains one of the more
promising technologies of tissue engineering. Nevertheless, the chondrocyte being a quiescent cell, the
expansion of the cell population to obtain a sufficient cell number for the surgical procedure appears critical
and in this regard the approach has some limitations: (a) if the damaged surface is particularly wide, the
availability of healthy cartilage to harvest appears limited; (b) in vitro expanded human articular
chondrocytes reduce their chondrogenic potential after 5-6 cell doubling.
Research is currently underway to develop alternatives to this protocol. Recent directions in cartilage
repair are moving towards the possibility to perform one-step surgery; several groups are analysing the
possibility to use mesenchymal stem cells (MSC) with chondrogenic potential and growth factors [19, 20,
21, 22, 26, 44, 60].
MSC have a self-renewal capacity and multi-lineage differentiation potential, which remain of great
interest for scientists involved in cell therapy and tissue engineering.
MSC can be characterized by their cultivation behaviour and their differentiation potential into
adipogenic, osteogenic and chondrogenic cells, as well as form bone, cartilage and fat [32, 37, 40, 55, 79].
Researches are currently exploring the possibility of manipulating stem cells in the laboratory to differentiate
into chondrocytes and which can then be integrated into a synthetic scaffold for later implantation. If MSC
are cultured in the appropriate microenvironment, they can differentiate to chondrocytes and form cartilage.
9

Onset of chondrogenesis requires a chemically defined serum free medium supplemented with
dexamethasone, ascorbic acid and growth factors such as TGF-B [72]. The micromass culture or pellet
culture system is generally considered a good in vitro model of chondrogenesis [44]. Johnstone et al cultured
MSC as pellets at the bottom of a tube for 2 weeks in a specific serum free cocktail medium. Under these
conditions cells organize a cartilaginous matrix by secreting proteoglycans and type II collagen and cells
appear as real chondrocytes embedded in their own matrix lacunae [40].
Ochi et al found that injection of cultured MSCs combined with a bone marrow stimulation
procedure in the chondral defect of rat model can accelerate the regeneration of articular cartilage. They
believed that this cell therapy was a less invasive treatment for the patients with cartilage injury [62].
Wakitani et al have used autologous culture expanded BMSC transplantation for repair of cartilage
defects in osteoarthritic knees. They chose 24 knees of 24 patients with knee O.A. who underwent a high a
high tibial osteotomy. Patients were divided into cell transplanted group and cell free group. After 16 months
follow-up, they concluded that M.S.C. was capable of regenerating a repair tissue for large chondral defects
[78]. Giannini et al [25] presented their one-step surgery procedure using MSC and scaffold.
In order to find a more effective and simple technique for cartilage repair, we have attempted to use
high concentration MSC combined with biologic scaffolds for osteochondral defect repair (Figures 7-06_1-
6). For this operative procedure, we firstly prepared the osteochondral defect with debridement by
arthroscopy or mini-open arthrotomy, and extracted bone marrow from iliac crest. High concentration MSC
was obtained by centrifuge (four to six times the baseline value). Then, we activate the bone marrow
concentrate and produce a sticky clot material. Finally, we paste BMC into the osteo-chondral defect and
cover it with a collagenic membrane. Due to the porous structure of the scaffold, we hypothesize it is easy
for adhesion, proliferation and differentiation of MSC. Preliminary data from our institution and other Italian
authors on MSC implantation with a one-step procedure seem to be promising, showing good clinical
outcomes at early follow up [32].
Plasma Rich in Growth Factors
The plasma fraction just above the red and the white cells is called plasma rich in growth factors
(PRGF). It is a plasma fraction with a high number of platelets; about three times the number of platelets in
blood [71]. In these platelets there is a high density of alpha granules, which contain proteins. PRGF is an
10

autologous preparation rich in growth factors, obtained from platelet-enriched plasma. Studies have been
carried out using PRGF in articular cartilage lesion treatment, and presented the following positive results:
PRGF can increase total G.A.G., collagen II synthesis and decrease degradation; induce chondrogenesis of
MSCs and promote chondrocyte proliferation, differentiation and adhesion [18].
PRGF contains different growth factors, such as PDGF, IGF-1, TGF-B, EGF, bFGF, VEGF, and
others. They regulate key processes involved in tissue repair, including cell proliferation, chemotaxis,
migration, cellular differentiation, and extracellular matrix synthesis [7]. Some growth factors in PRGF show
good activity for chondrogenesis. Barry F et al demonstrated MSC cultured with TGF-β produced
significantly more proteoglycans and collagen II [5]. Fukumoto T et al found that IGF-1 has a synergistic
effect with TGF- β in promoting MSC chondrogenesis [23]. The studies by Stevens MM et al have shown
that bFGF induce M.S.C. proliferation and chondrogenesis [76].
Cugat et al have used PRGF treating chondral defects and have obtained good results. According to
their experiences for other connective tissue repair, they think that PRGF in physiological concentrations is
effective for the recovery of connective tissue. Local treatment is safe and does not alter the systemic
concentrations of these proteins [18].
Kon et al [41] have studied a group of 30 patients with symptomatic degenerative disease of the knee
joints treated with three PRP intra-articular injections weekly; the follow up at 6 months showed positive
effects on the function and symptoms.
We have also attempted to use PRGF combined with a scaffold for osteochondral defects. We
hypothesized that penetration of subchondral plate would allow the release of MSC, which provide the cell
source for cartilage repair. 23 patients with a mean age of 44.3 years, among a group of 50 patients, were
followed-up. We collected pain visual analogue scale (VAS) and KOOS score at pre-treatment, 3 and 6
months post-treatment, and the preliminary results are encouraging. There was a trend towards improvement
in both scores. PRGF can induce MSC chondrogenesis, promote cell proliferation and increase deposition of
ECM.
Recently authors have proven synergistic effects of PRP combined with MSC. Nishimoto et al [59]
suggested that simultaneous concentration of PRP and bone marrow cells (BMC), could play important role
in future regenerative medicine. Milano et al [50] in an in vivo study showed a more effective cartilage repair
11

after microfracture associated to hydro gel scaffold with PRP. Finally, several authors [1, 25, 26, 57, 61, 62,
78, 79] have stated that growth factors could act like as a carrier to fix chondrocytes into cartilage defects
and can be combined with mesenchymal stem cells. Preliminary data are encouraging but further studies on
clinical efficacy will clarify if simultaneous use of PRP and MSC could represents a real solution for
regenerative medicine in cartilage repair.
However, application of growth factor proteins is hampered by their short pharmacological half-life.
This has let to the application of gene transfer to achieve a localized delivery into the defect of therapeutic
gene constructs. Among the most studied candidates, polypeptide growth factors have shown promise to
enhance the structural quality of the repair tissue. These studies show less morbidities and complications
inherent to cartilage surgical techniques by lessening surgical procedures translating to lower cost for the
patient. However, medium-term prospective randomized studies are suggested to confirm these short-term
results.
CONCLUSIONS
A number of viable options have been made available over the years to address problems concerning
cartilage damage and each technique has its advantages and disadvantages. Numerous studies are currently
under way to clarify some of the questions that still remain unanswered regarding the long-term durability of
these procedures and the possible modifications that can still be made to achieve better results.
From an initial arthrotomy approach, some of the techniques can now be entirely performed
arthroscopically. This modification has enabled surgeons to avoid possible intra-operative problems and
decreased operative time. By eliminating the need for an open procedure and harvesting of periosteal flap,
joint trauma is significantly reduced. Complications, such as graft hypertrophy and ossification are also
avoided with the use of this three-dimensional hyaluronic acid scaffold.
At present, not all lesions can be addressed with a single technique. Retropatellar, tibial plateau and
posterior condylar lesions remain a challenge. Development of better instruments and introduction of new
techniques in the near future should be able to solve this dilemma.
Characterized Chondrocyte Implantation is a second-generation ACI procedure and improves
chondrocyte selection to form stable and consistent hyaline cartilage.
12

Biotechnology is progressing at a rapid pace, allowing the introduction of numerous products for
clinical application. The research on the identification or creation of the ideal material for engineering
cartilage substitutes has been very prolific in the last decade. The use of polymers, both natural and
synthetic, that undergo controllable bulk erosion or resorption have been largely investigated as they could
represent a favorable solution for engineering cartilage tissues in vitro or in vivo.
An important issue to be addressed for the future perspective for cartilage repair is the quality of the
bonding and the integration of the newly formed tissue to the native tissue, and several studies seem to
demonstrate the importance of both cells and the new matrix to achieve a stable healing. This possibly would
lead to the generation of tissue-engineered strategies for the repair of complex lesions involving cartilage,
together with the subchondral bone and other structures. Several scaffolds have been tested in animal models
for regenerating cartilage tissue. However, carefully conducted randomised prospective studies for each of
these innovations should be carried out to validate their efficacy for cartilage regeneration.
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18

1
STEM CELL BIOLOGY: FACT,
FICTION AND OPPORTUNITY
January 27-28, 2012
C. Thomas Vangsness, JR., M.D.
Professor of Orthopaedic Surgery
Chief of Sports Medicine
Keck School of Medicine
University of Southern California
Los Angeles, California
vangsness@usc.edu
1. What is a Stem Cell?
a. A stem cell is a cell that has the ability to divide (self replicate) for
indefinite periods – often throughout the life of the organism. Under the
right conditions, or given the right signals, stem cells can give rise
(differentiate) to the many different cell types that make up the organisms
(plasticity).
b. Naturally-occurring living cells that haven’t yet differentiated into the
specialized cells.
c. Part of the body’s repair system, and can divide to replenish other cells.
d. Each new cell has the potential to become a cell with a more specialized
function such as a red blood cell, bone marrow cell, muscle cell, nerve
cell, etc.
e. Stem cells have the ability to divide asymmetrically-one portion of the cell
division becomes a differentiated cell while the other becomes another
stem cell.
f. Discovered at University of Wisconsin 1998-James Thomson
2. Difference Between an Embryonic Stem Cell and Adult Stem Cell
a. Embryonic stem cells are isolated from embryos only a few days old.
i. Used to create stem cell “lines” – cultures that can be grown
indefinitely in the laboratory and widely distributed to researchers.
ii. Potential to develop into any type of cell in the body.
b. Adult stem cells are found in many body parts such as cardiac tissue, liver
and bone marrow
c. Mesenchymal stem cells (MSC’s) are found in the bone marrow in
varying quantities. Rare in numbers, approximately 1 in 100,000 cells
(which will vary inversely with age).
d. Scientists are only beginning to understand the mechanisms involved.
e. Embryonic stem cells function to generate new organs and tissues.

2
f. Adult stem cells function to replace cells during the natural course of cell
turnover.
g. Researchers continue to explore where stem cells might reside in the body
and how many different organs in the body contain stem cells.
3. Why are Doctors and Scientists So Excited About Them?
a. Hold enormous promise for helping to understand and treat a wide variety
of diseases and disorders.
b. Research can provide unprecedented insight into cell interactions, cancer,
birth defects and other disorders that develop during cell growth and
transformation.
c. Could become a renewable source of replacement cells and tissues that
could be used to treat illnesses, conditions and disabilities.
4. Are Stem Cells Being Used Successfully to Treat Any Human Disease?
a. Blood-forming stem cells in bone marrow called homatopoietic stem cells
(HSCs) are routinely being used to treat disease.
b. Doctors are transferring these cells as bone marrow transplants for more
than 40 years.
c. Treat: leukemia, lymphoma and several inherited blood disorders.
d. Only adult stem cells have been tested in humans.
e. Tests have taken place in very limited clinical studies.
5. The Controversy
a. The mass of cells created during nuclear transfer is known as a blastocyst,
or an early embryo, which theoretically could be implanted into a uterus to
produce a baby.
b. Groups that oppose abortion have objected to this research on the grounds
that creating an embryo through nuclear transfer, only to destroy it to
obtain the stem cells, is tantamount to destroying a human life. Newer
technologies are moving past this.
c. 1996 Law prohibits tax payer dollars in work that harms an embryo – law
suits and appeals persist.
d. In 2001, President Bush issued an executive order limiting federal funding
of embryonic stem cell research to about 60 stem cells lines obtained from
discarded embryos created in the in vitro process at fertility clinics. The
order does not pertain to privately funded research.
e. Scientists hope to find stem cells in the adult body that have a greater
plasticity or potency – the ability to divide into multiple cell types.

3
6. Media Influence
a. Controversy and confusion commonly present in the media.
b. Issues of Cloning
c. Abortion Debate
-This is rapidly becoming a moot point.
d. False promises of treatments
7. U.S. Technology Leader
a. United States controls most of the world’s stem cell patents.
b. June 2004, there were approximately 5,125 stem cell patents worldwide.
c. 75% of these were held by U.S. companies and academic institutions.
d. Top 30 stem cell corporations only hold close to 10% of all patents.
e. The majority of stem cells patients are controlled by the government and
academia.
f. 5% of all patents are embryonic stem cell related.
g. 2000 and 2004, the United States filed for patents four times as often as
Japan. Australia and England combined.
8. Government Funding
a. 80% of NIH’s funding to 50,000 researches at 2.800 universities, medical
schools and research institution
b. 10% of the NIH’s budget goes to its own laboratories, most of which are
in Bethesda, Maryland and 6,000 scientist.
c. FY 2002-2010 the NIH funded approximately 2.85 billion for human stem
cell research and 4.3 billion for non human stem cell research.
d. September 2010: Obama admisistration expands the number of stem cells
for government funding. Re-expanded to 142 hESC in December 2011.
e. ClinicalTrials.gov
i. Stem Cells -3861
ii. Stem Cells – Orthopaedic Surgery -24
9. State Funding
a. 2004 Propsition 71 in California
i. California Institute for Regenerative Medicine.
ii. 3 Billion (300 Million/year for 10 Years).
b. Several other states are getting involved with much smaller proposals.
10. The Future
a. Continued increase in funding
b. More understainding of the biology of cell to cell interactions and
commumication.
c. Increase in clinical trials
d. Minimal Evidence-Based Medicine to date.

4
11. Most Advanced Stem Cell Companies

12 th International Sports Medicine Fellows Conference
January 27-29, 2012● Carlsbad, California
12:30 PM - 14:30 PM Session 3
Session III
12:30 PM - 13:00 PM Non-Operative Treatment - Viscosupplementation or PRP Alberto Gobbi, MD ITALY
13:00 PM - 13:15 PM
Nutrition and Cartilage Management; Glucosamine and
What Else?
Jason Theodosakis, MD USA
13:15 PM - 13:30 PM Future Approaches to Cartilage: Growth Factors Susan Chubinskaya, PhD USA
13:30 PM - 13:45 PM
Overview - Algorithm for Cartilage Care: Where Do We
Go From Here?
Jason Scopp, MD USA
13:45 PM - 14:00 PM The New Frontier of the Hip Jason Snibbe, MD USA
14:00 PM - 14:15 PM
Product Challenges for Partial Thickness Articular
Cartilage Treatment
Wayne Augé II, MD USA
14:15 PM - 14:30 PM The Business of Cartilage Repair Ralph Gambardella, MD USA
14:30 PM - 14:45 PM Discussion

Introduction
“Non-Operative Treatment – Viscosupplementation or PRP”
Alberto Gobbi, Kenneth Zaslav, Georgios Karnatzikos, Anup Kumar
Articular cartilage damage of the knee is becoming increasingly identified as a source of
functionally limiting injuries in athletes 1, 2 . Cartilage has long been recognized as having
limited intrinsic healing potential 3 by the fact that it is avascular, has very few and
specialized cells with a low mitotic activity and the lack of undifferentiated cells that can
promote tissue repair. Once cartilage is injured it gradually degenerates, leading to
Osteoarthritis (OA) 3, 4 . Many conservative treatment options such as Glucosamine,
Chondroitin Sulfate and other dietary, diacerein and intra-articular and viscosupplementation
have been utilized for the treatment of OA. Platelet-rich Plasma (PRP) intra-articular
injections represent a therapeutic option with promising preliminary clinical results.
Glucosamine, Chondroitin Sulfate and other dietary supplements
Glucosamine (G) 1,500-2,000 mg/day and Chondroitin Sulfate (Cs) 800-1,200 mg/day and
Avocado-Soy Unsaponifiables (ASU) 300-600 mg/day taken together or alone are useful as
adjunct therapies in cartilage disorders 5 . Basic science studies indicate more anti-catabolic
than anabolic effects, and all three probably act as signal modulators of inflammatory and
degredative enzyme pathways. 6-8 Some animal evidence indicates pre-treatment with G, Cs,
or ASU might delay the course of OA after traumatic injury, 9-11 but without human evidence,
prophylactic use of these supplements cannot be recommended. G, Cs and ASU have
NSAID-sparring effects. 12, 13 In acute pain, co-administration of fast acting agents such as
acetaminophen or NSAIDs with G, Cs and/or ASU, followed by prompt removal of the
former, may be advised. Most of the 50+ human clinical trials on G, Cs, or ASU, have
shown positive results either for structure modifying effects or pain/function
improvement. 14-19 20, 21
Importantly, structural benefits were independent of symptom relief.

Viscosupplementation
Viscosupplementation with intra-articular injection of exogenous Hyaluronic acid, has an
integral role in the treatment algorithm of osteoarthritis and cartilage damage.
The healthy human knee contains approximately 2cc of synovial fluid. In the
osteoarthritic knee, the concentration of HA is reduced to one-half to one-third of the
normal value. 22 Endogenous HA is produced by the type B synoviocytes and fibroblasts
of the synovium and its role is multifactorial. 22 It provides joint lubrication and absorbs
shock, while also promoting chondrocyte proliferation/ differentiation. 23-25 HA has also
been shown to inhibit tissue nocioceptors and stimulate endogenous hyaluronan
formation 26 Viscosupplements have both chondroprotective and anti-inflammatory
effects. 27 Chondroprotection occurs through down regulation of the gene expression of
osteoarthritis-associated cytokines and enzymes. 28 The anti-inflammatory effect occurs
by down regulation of TNF-alpha, IL-8 and iNOS in synoviocytes. 27
These chondroprotective effects have driven the use of viscosupplementation in the post-
operative knee. Pain that persists after arthroscopy can be decreased with the use of
Hyaluronic acid injection. It has been shown to result in decreased joint swelling and to be
NSAID sparing. 29 Additionally, the disease modifying effects of HA have been shown to
reduce cartilage degeneration and promote tissue repair after micro-fracture in an animal
model. 30, 31 This occurs by inhibiting the production of nitric oxide and by stabilizing
32, 33
proteoglycan structure.
Platelet-Rich Plasma (PRP)
PRP can be defined as the volume of the plasma fraction from autologous blood with
platelet concentration above baseline (200000 platelets/µl). 34 PRP contains different
growth factors, which regulate key processes involved in tissue repair. 35, 36 The rationale
for topical use of PRP is to stimulate the natural healing cascade and tissue regeneration
by a “supra-physiological” release of platelet- derived factors directly at the site of

treatment. PRP has been successfully used in surgical and outpatient procedures in the
treatment of several musculoskeletal problems. 37-39
While recent published RCT’s using PRP in the Achilles and Rotator cuff tendons have
shown little to no statistical improvement, various authors have used PRP to treat chondral
defects in athletes and obtained good results. 40, 41 We prospectively followed up 50 patients
active in sports with degenerative lesions of the knee 42 . All patients were treated with
two intra-articular injections (one monthly) with autologous PRP (Regen® ACR-C,
RegenLab, Switzerland) (Fig.1a-d). Study revealed that the use of PRP in patients with
chronic degenerative disease of the knee could act to diminish pain and improve symptoms
and quality of life. A prospective randomized study comparing PRP to HMW HA as well
as LMW HA reported superior outcomes at 6 months with PRP injections. 43
Figure 1. PRP preparation: a) blood aspiration b, c) centrifugation of the blood sample
d) fraction of PRP after centrifugation (yellow upper part in tube)

Role of Pulsed Electromagnetic Fields (PEMFs)
Pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs), with specific
physical signal parameters 44 , in vitro favour the proliferation of chondrocytes, stimulate
proteoglycan synthesis and demonstrate an A2A adenosine receptor agonist activity 45-47 . In
vivo, PEMFs prevent degeneration of articular cartilage and down-regulate the synthesis
and release of pro-inflammatory cytokines in the synovial fluid 66-68 . We prospectively
followed up 22 patients treated with PEMFs (I-ONE therapy, IGEA, Carpi, Italy) therapy 50
for 1 year (fig. 2). Patients showed significant improvement in all scores at final follow up
(p < .005).
CONCLUSION
Figure 2: I-ONE PEMFs generator
A number of conservative treatment options have been utilized in order to prevent progression
of OA. PRP represents a user friendly therapeutic application, which is well-tolerated and
shows encouraging preliminary clinical results in active patients with knee OA.

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Knee Surgery. 2010; 9(3): 132-138. doi: 10.1097/BTK.0b013e3181ef5012

41. Kon E, Filardo G, Di Martino A, Marcacci M. Platelet-rich plasma (PRP) to treat
sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc. 2011
Apr;19(4):516-27. Epub 2010 Nov 17. Review.
42. Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich Plasma treatment in
symptomatic patients with knee Osteoarthritis: Preliminary results in a group of active
patients. Sports Health: A Multidisciplinary Approach, (In Press).
43. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari
PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular injection versus
hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early
degeneration to osteoarthritis. Arthroscopy. 2011 Nov;27(11):1490-501. Epub 2011 Aug
10.
44. De Mattei M, Fini M, Setti S, Ongaro A, Gemmati D, Stabellini G, et al.
Proteoglycan synthesis in bovine articular cartilage explants exposed to different low-
frequency low-energy pulsed electromagnetic fields. Osteoarthritis Cartilage.
2007;15(2):163-8.
45. Varani K, Gessi S, Merighi S, Iannotta V, Cattabriga E, Spisani S, et al. Effect of low
frequency electromagnetic fields on A2A adenosine receptors in human neutrophils. Br J
Pharmacol. 2002;136(1):57-66.
46. Varani K, De Mattei M, Vincenzi F, Gessi S, Merighi S, Pellati A, et
al. Characterization of adenosine receptors in bovine chondrocytes and fibroblast-like
synoviocytes exposed to low frequency low energy pulsed electromagnetic fields.
Osteoarthritis Cartilage. 2008;16(3):292-304.
47. De Mattei M, Varani K, Masieri FF, Pellati A, Ongaro A, Fini M, et al. Adenosine
analogs and electromagnetic fields inhibit prostaglandin E(2) release in bovine synovial
fibroblasts. Osteoarthritis Cartilage. 2009 Feb;17(2):252-62.
48. Fini M, Torricelli P, Giavaresi G, Aldini NN, Cavani F, Setti S, et al. Effect of pulsed
electromagnetic field stimulation on knee cartilage, subchondral and epiphyseal

trabecular bone of aged Dunkin Hartley guinea pigs. Biomed Pharmacother. 2008
Dec;62(10):709-15.
49. Benazzo F, Cadossi M, Cavani F, Fini M, Giavaresi G, Setti S, et al. Cartilage repair
with osteochondral autografts in sheep: effect of biophysical stimulation with pulsed
electromagnetic fields. J Orthop Res. 2008 May;26(5):631-42.
50. Gobbi A, Karnatzikos G, Malchira S, Maggi L, Ongaro A. The use of pulsed
electromagnetic fields in symptomatic patients with degenerative cartilage lesions of the
knee: a preliminary report. Journal of Sports and Traumatology (In Press).

Dr. Theo
Nutrition and Cartilage Management:
Glucosamine and What Else?
Jason Theodosakis, MD, MS, MPH, FACPM
“Dr. Dr. Theo” Theo
University of Arizona College of Medicine
Tucson, Arizona
drtheo.com / drjtheo@gmail.com
How Should You Use/Prescribe
Supplement for Joint Health?
• For symptom relief
• To reduce need for acetaminophen/NSAIDs
p
• For structure modification/delay of OA
progression
• As an adjunct to cartilage repair surgeries?
Prescription DMOADs do not exist
for OA, and pharmacologic agents
are known to have serious
adverse events
Some dietary supplements have
DMOAD action, are safe and should
be used as co-first line agents, but
there is a lot of hype and concerns
about product quality and efficacy
1
3
Disclosures
Stock Ownership, Past Speaker: Pfizer
Consultant and/or Grants: Bioiberica,
Ownership/Officer: Supplement Testing Institute -
“Dr. Theo’s ® Dr. Theo s ” Joint health products manufacturer and
seller, sell GS on website
Book Author
Future OA Therapy (Speculation) - Tailor made?
OA Tyype
Dr. Theo
Ia
Ib
IIa
IIb…
Pharmacogenomic Profile
A1 A2 B1 B2…
Optimal Pharmacologic
Therapy
= COX/5-LOX Inh.
= G/CS
= Diacerrhein
= IL-1 RA
=ASU = ASU
= HA injection
= NO NSAID
Other Factors: Age, OA grade, location of lesions, biomechanical factors, etc.
Acetaminophen is not that safe
or effective
• No Significant DMOAD studies published through 12/11
• Several pain/function studies are null, especially long-term 1-4
• Safety is becoming more and more of an issue …
– #1 cause of accidental and intentional acute liver failure in the US 5
– Even short-term use (2 weeks) can elevate LFTs 6
– Even low-dose (>500 mg/day) chronic use is associated with 2x HTN
incidence in middle-aged women 7
– Toxic/Lethal dose is only 2.5x7 /8x of max daily dose (4 gm/day)
Dr. Theo
1- Case JP. Arch Intern Med. 2003;163:169-178
2- Miceli-Richard C. Ann. Rheum. Dis. 2004:923-30
3- Pincus T. Ann Rheum Dis. 2004;63;931-939
4- Herrero Herrero-Beaumont Beaumont G. Arth & Rheum 2007. 56;2
pp 555 555-567. 567.
•
5- Larson AM. Hepatology 2005;42:1364-72
6- Watkins P. JAMA 2006;296:87-93
7- Forman JP. Hypertension. Vol. 46(3), 9/2005, pp 500-507.
8- Hung OL. Emergency Medicine: Comprehensive Study Guide
6 th Ed (2004) Section 14; 171.
4
6
1

NSAIDs are not that safe and offer
only short-term symptom relief
• No Significant DMOAD studies published through 12/11
• All long-term pain/function studies are null 1-4
GI safety benefits of Celebrex ® • GI safety benefits of Celebrex are lost with the addition of
® are lost with the addition of
prophylactic aspirin
• Chronic NSAID usage often requires co-administration of
PPIs
Dr. Theo
1- Case JP. Arch Intern Med. 2003;163:169-178
2- Miceli-Richard C. Ann. Rheum. Dis. 2004:923-30
3- Pincus T. Ann Rheum Dis. 2004;63;931-939
4- Herrero Herrero-Beaumont Beaumont G. Arth & Rheum 2007. 56;2
pp 555-567. 555 567.
Copyright ©2005 American Physiological Society
5- Larson AM. Hepatology 2005;42:1364-72
6- Watkins P. JAMA 2006;296:87-93
7- Forman JP. Hypertension. Vol. 46(3), 9/2005, pp 500-507.
8- Hung OL. Emergency Medicine: Comprehensive Study Guide
6 th Ed (2004) Section 14; 171.
Rationale for Weight Loss
Intra-abdominal fat creates chronic low-grade systemic inflammation
Petersen, A. M. W. et al. J Appl Physiol 98: 1154-1162 (2005)
Mediterranean Diet
Fat as an endocrine
organ (especially
omental fat)
7
9
11
What About Weight Loss?
Effect of weight reduction in obese patients diagnosed
with knee osteoarthritis: a systematic review and
meta-analysis
• 35 trials identified; 4 RCTs (5 comparisons) included (N=454)
• Pooled ES for a weight reduction of ~6 kg:
– pain 0.20 (0 - 0.4)
– disability 0.23 (0.04 - 0.4)
• Disability improved significantly when weight was reduced
>5% or at a rate >0.24% per week
• Clinical efficacy for pain was evident, but not predictable
Christensen, et. al. Annals of the Rheumatic Diseases 2007;66:433-439
About 90% of Arthritis Patients
Use Dietary Supplements – Why?
• “Conventional medicine is not optimally effective
• Drugs frequently have adverse effects
• Herbal medicines are heavily yp promoted, , for example, p , by ythe
popular press, Internet sites, popular books, and celebrities
• Herbal medicines are widely available, usually marketed as food
supplements
• Exaggerated claims are often made regarding their efficacy
• The public tends to view herbs as natural and thus devoid of risks
• Most consumers can afford the extra costs for herbal medicines”
Dr. Theo
Ernst E. Rheum Dis Clin N Am 37 (2011) 95–102
8
10
12
2

What Supplements May Help Gout?
• Lifestyle modification and prescriptions are
quite effective
– Xanthine oxidase inhibitors, Uricosuric agents
– New URAT 1 inhibitor, IV pegloticase
• No major definitive supplement trials
• Vitamin C has most evidence
• Cherries and glucosamine may be of benefit
Dr. Theo
Osteoarthritis - Evolving Definition
“Osteoarthritis is a disorder involving movable joints
characterized by micro- and macro-injury–initiated cell
and extracellular matrix degeneration that activates
Dr. Theo
maladaptive l d ti repair i responses, iincluding l di sterile t il
autoinflammatory pathways of innate immunity, bone
remodeling, and osteophyte formation.”
Virginia Kraus MD, PhD 2011
Nutraceutical Interventions for Cartilage/OA
Dr. Theo
• ASU (Avocado-Soybean Unsaponifiables)* 300-600 mg
• Chondroitin* 800-1,600 mg (≥ USP Grade, single animal origin)
• Glucosamine* 1,500-3,000 mg
• SAM-e (s-adenosylmethionine)* 800-1,600 mg
* Also sold as OTC or Prescription drugs in some countries
13
15
17
Dr. Theo
Trauma
Vitamin C and Serum Uric Acid review article
NF-�B NF-�B
I-�B I-�B
Summary
Median 500 mg C
Reduction -0.35 mg/dl
P = 0.032
NF-kB activation pathway
Grimm et al., J Inflamm 3: 1-5, 2006
• 200-2,000 mg
• Heterogeneous
populations and
research designs
• Uric acid levelsnot
gout attacks
evaluated
Juraschek SP. Arthritis care
& research. 63(9):1295-306,
2011 Sep
Nutraceutical Interventions for Cartilage/OA
Secondary agents
Dr. Theo
• MSM (methylsulfonylmethane) 1,500-6,000 mg
• Anti-inflammatory enzymes*
• Hyaluronic Acid, Oral 80 mg - 240 mg/day
• Omega-3 Fish Oil 2 gm & up of Omega-3, especially EPA
• French Maritime Pine Bark Extract 100 100-150 150 mg
• Herbal derivatives
– Devil’s Claw 1,800 to 3,600 mg
– Boswellia 300 – 3,000 mg
– Rose Hips 2,250 mg
– Curcumin-phosphatidylcholine complex 1,000 mg
• Egg Shell Membrane 500 mg
* Also sold as OTC or Prescription drugs in some countries
14
18
3

Effect Sizes for Pain Improvement in
Major OA Treatments (Es pain, 95%Cl, Level of Evidence)
Acupuncture 0.35 (0.15, 0.55), la
Weight reduction 0.20 (0.06, 0.33), la
Electrotherapy/EMG 0.15 (-0.09, 0.39), la
Glucosamine sulphate 0.40 (0.15, 0.64), la
Chondroitin sulphate p 0.68 (0.43, ( , 0.93), ), la
ASU 0.38 (0.01, 0.76), la
Acetaminophen (paracetamol) 0.15 (0.01, 0.76) la
NSAIDs 0.29 (0.22, 0.35), la
Topical NSAIDs 0.44 (0.27, 0.62), la
Opioids 0.37 (0.23, 0.51), la
IA corticosteroid 0.55 (0.34, 0.75), la
Zhang W, Moskowitz R, Nuki G. OARSI Treatment Guideline Committee ACR 10/2008 Includes studies published up to 1/31/08
ASU - Research Review
• Five, randomized, double-blinded, placebo-controlled
human clinical trials lasting three months to two years in
duration 1-4
• Three studies positive for pain and function
improvement 1-3 and NSAID use reduction 3
improvement 1 3 and NSAID use reduction 3
• Two studies evaluated Joint Space Width (JSW) of hip
on X-Ray 4-5
• Meta-Analysis: “Give ASU a chance for e.g. 3 months;
Knee results>hip” 6
1- Blotman F. Rev Rheum 1997;64(12);825-834
2- Maheu E. Arth & Rheum 1998;41(1):81-91
3- Appelboom T. Scand J Rheum 2001;30:242-7
4- Lequesne M. Arth & Rheum 47:50-58, 2002
5- Maheu E. Ann Rheum Dis 2010;69(Suppl3):150
6- Christensen R. OA&Cart 2008;6,399-408
SAM-e (S-Adenosyl- L-methionine)
• Naturally occurring methyl donor used as a drug in
Europe for treatment of depression, OA and intrahepatic
cholestasis
• Dose used in OA studies = 800 - 1,600 mg
• Symptom, but no disease-modifying data for OA
• Onset of action 8-12 weeks
Dr. Theo
19
21
23
All herbal medicines should be
ceased 2 weeks before surgery
The peri-operative implications of herbal medicines
P. J. Hodges and P. C. A. Kam
Anaesthesia. Volume 57; Page 889 - 9/2002
SAM-e (S-Adenosyl- L-methionine)
• Equivalent effect overall to low-dose NSAIDs or placebo for OA
pain and anti-depressants for mild/moderate depression (but with
less side effects than prescription anti-depressant drugs)*
• Effect size of studies lower than that for glucosamine/chondroitin g
or
ASU
• Synthetic version appears to be less active - common in retail
brands in US
• Too expensive for general use. Reserve for OA/depression combo
Dr. Theo
Dr. Theo
* Agency for Healthcare Research and Quality (AHRQ)
Publication No. 02-E033, August 2002. Agency for
Healthcare Research and Quality, Rockville, MD.
What’s New in
Glucosamine/Chondroitin?
• Once daily & 4-6 month trial for symptom relief
• Symptom relief unrelated to structural effect
• D Dose (1 (1,500 500 mg glucosamine) l i ) may bbe llow
• Should use of 800 mg chondroitin now be
mandatory?
• Chondroitin evidence is very strong at 800 mg, ≥
USP Grade, single animal sourced
22
24
4

Example of what happens in a long-term OA Study
Dr. Theo
Dr. Theo
Meta-Analysis of Chondroitin Sulfate for Structure
Modification
Positive effect size (0.26), highly statistically significant p< 0.0001
Chondroitin can beneficially affect structure independent of symptom modification
Even with the addition of GAIT part II, the effect size was 0.22
and still significant (Hochberg, OARSI 2008)
Hochberg M, et. al. Current Medical Research and Opinion Vol.24, No. 11, 3029-35 (2008) 27
Chondroitin Biologic Activity Variation
• Testing in vitro biologic activity of 10 chondroitin raw
materials on bovine chondrocytes
• About half had either reduced activity or activity not
significantly different from negative control
Int’l Cartilage Repair Society Meeting, San Diego 1/06
25
29
TID Dosing May Lower Glucosamine’s Peak Plasma Concentration
Dr. Theo
[
Peak Plasma
Concentration
C max (µM)
GS 1.5 g/day over 3 days 1 8.9
G•HCL 1.5 g One-Time Dose 2 3.0
G•HCL 0.5 g TID Multiple Dose
over 12 weeks 3
1.2
3,000 mg GS
13.3 µM
Glucosamine IC50 on IL-1b-stimulated gene expression 4
Marker iNOS TNF-a COX-2 MMP-3 IL-1b IL-6 ADAMTS5 NF-kB Subunits
P50 p52 p65 RelB
IC 50 (µM) 13.8 12.8 11.2 10.2 6.2 4.4 2.8 0.4 / 0.6 / 1.0 / 0.3
Dr. Theo
Dr. Theo
1- Persani S. Osteoarthritis and Cart. 13, 1041-1049 (2005)
2- Jackson CG. ACR 2005 meeting Late Breaking Abstract L13
3- Jackson CG. ACR 2006 meeting Poster 352
4- Piepoli et al, Arthritis Rheum 2005; 9 Suppl: 1326
• 69 patients with synovitis, 800 mg CS or Placebo, 6 mo then all
given CS for 6 months more
• Symptoms similar between groups but:
– At 6 months, CS group had less cartilage volume loss in global knee, lateral
compartment, and tibial plateaus (p = 0.030, 0.015 and 0.002)
– At 12 months, CS group lower BML scores in Lat compartment and Lat
femoral condyle (p = 0.035 and 0.044)
Ann Rheum Dis 2011;70:982-89
Glucosamine/Chondroitin Safety
• “Anything that has an effect can have an adverse effect”
Theodosakis 1995
• Case Reports
– INR values may be affected with lower quality chondroitin
– Skin rashes have been reported for shellfish based glucosamine,
especially in those with shellfish anaphylaxis history
• No binding to plasma proteins, no use of Cytochrome
enzymes
• No statistically significant difference has been in any human
controlled or observational trial to date, compared to
placebo, for up to 8 years of assessment
26
28
30
5

What are the chances that
Glucosamine and Chondroitin are
Placebos?
• Most studies show statistically significant effects on
primary or secondary outcome measures such as
pain, ffunction, quality of f life, f joint space narrowing,
cost effectiveness
• In no instance out of > 100 study arms has a
placebo resulted in a statistically significant better
primary or secondary outcome than G/CS
• Odds of this due to chance are astronomical
Dr. Theo
Dr. Theo
Dr. Theo
Chondroitin Effect Size Review
31
Long-term structure
studies that were
positive for
structure
changes, but not for
pain (since subjects
had little pain to
start)
Reichenbach S. Ann
Intern Med.
2007;146:580-590.
Was GAIT 1 Falsely Negative?
• Before even evaluating the effect of the
supplements, the effect of the active comparator
drug (celecoxib) must be similar to all other
celecoxib studies or the study may be void
• 3 ways to determine the effect of the active
comparator drug:
– Study outcome measures X - 40/42 failed
– Clinical relevance of treatment effect
– Effect Sizes
X – Not 15% > Placebo
X X – Not Clinically Relevant or Statistically Significant
33
35
Dr. Theo
Dr. Theo
Why Doesn’t Glucosamine and
Chondroitin “Work” in Some
Patients?
• What does “Work” Mean?
– Less pain? p Improved p activity y tolerance? Less
Stiffness?
– Decreased use of medications?
– Less need for surgery or physical therapy?
– Lower overall cost of care?
Pharmacological response to Chondroitin as a function of
baseline pain intensity and duration of treatment
(data from Reichenbach et al. Ann Intern Med 2007;146:580-90)
90
80
70
60
50
40
30
Responders VAS/Lequesne
Non responders VAS/Lequesne
Non responders WOMAC
20
0 3 6 9 12 15 18 21 24
Duration of treatment (months)
War- Supplements vs Drugs
• Manufacturers hype/skew data
• Studies are designed or performed
improperly to get intended result
– Improper dose, form, or outcomes are used
– Meta-analyses are altered to include
inappropriate studies
– Structure studies are used to negate positive
pain data
32
36
6

Dr. Theo
Some of the Negative (Null) Studies on G/CS are so
flawed that they should not even be included in the
argument against G/CS effectiveness
• Uncontrolled use of NSAIDs, opiates,
acetaminophen
• Insufficient dose of supplements
• Insufficient duration of the study
• Mixed conditions/joints being studied
• Inappropriate outcome measures
No Excuse for having low levels of
Vitamin D
• Work in sun w/o sunscreen and only partially
clothed - problem: your dermatologist
• Measure levels: optimal appears to be about 50
ng/ml (conversion to nmol/L: multiply by 2.5)
• Most people need 1,000-5,000 IU by
supplements
• With low levels, 1,000 IU raises serum by about
10 ng/ml, but less as level rises
Oral HA Products
• 3 main origins of HA raw material
– Low HA concentration (mainly collagens, e.g. BioCell ® )
– High HA concentration extracted from Avian sources (e.g. Hyal-Joint ® )
– Fermented (China, e.g. HyaMax®)
• Evidence (Avian)
– 1 pilot DBPC clinical positive for improved pain, ADLs and QOL
– 2 positive human pain/synovitis studies: effect > acetaminophen
– Equine oral absorption/effect study at human equivalent dose
– Several positive basic science mechanism studies
Dr. Theo
37
39
41
HSA - Health Savings Accounts
FSA - Flexible Spending Accounts
www.irs.gov/pub/irs-pdf/p502.pdf
MSM (Methylsulfonylmethane)
• Naturally occurring sulfur-containing supplement
• Anti-oxidant and anti-inflammatory properties
• In-vitro and animal study- anti-inflammatory @ 6g/d
• 3 pilot studies on OA pain and function
– 1,500 mg/day Indian study1 3 000 mg/day Israel study2 – 3,000 mg/day Israel study2 – 6,000 mg/day US study 3
• Lower doses (e.g. 500 mg) may help offset sulfur
losses in cartilage due to OA and medication use
• Use distilled product to reduce the risk of DMSO or
heavy-metal contaminants
1- Usha, et. al. Clin. Drug Investigations. 24:6;pp.353-63
2- Debi, et. al. OARSI 2007
3- Kim, et. al. OA & Cartilage 14:(2006), 286-294
Omega-3 considerations
• Oxidized oil (rancid) is proinflammatory
• People convert short chain to long chain oils
variably (fish oil may be better than others)
• Cod liver oil - too much Vit A?
• TG vs. EE form
• EPA/DHA ratios
Supplements
7

Study Number of
patients
Pain Joint stiffness Physical
function
Farid et al. 37 -43 % -35 % +52 %
Cisar et al 100 -40 % -40 % *
+22 % *
Farid et al. 37 -43 % -35 % +52 %
Cisar et al 100 -40 % -40 % *
+22 % *
Cisar et al. 100 -40 % -40 % +22 %
Belcaro et al. 156 -55 % -53 % +56 %
Farid et al., Nutr Res, 27:692-697, 2007
Cisar et al. Phytother Res 22: 1087-1092, 2008 (* = 2 month results)
Belcaro et al. Phytother Res, 22: 518-523, 2008
Key Points
• The evidence for most dietary supplements or nutraceuticals
in OA is incomplete
• The four that are OTC or prescription drugs throughout the
world do have good evidence (ASU, glucosamine,
chondroitin, , SAMe) )
• The risk/benefit/cost ratio of the first three is better than that
of other pharmacologic interventions for OA
• Vitamin D levels should be optimized in all patients
• Some herbals like curcumin, boswellia and oral, avianderived
Hyaluronic acid appear to be promising
Dr. Theo
Book - Integrative OA Treatment Program
Purpose: How-To guide to get patients directly involved in care, integrate all areas of
treatment and reduce the time needed to educate patients. 8th grade reading level.
Nine Steps:
1. Accurate diagnosis, modify
reversible contributors to OA
2. Use glucosamine and
chondroitin (& ASU)
3. Improve biomechanics
4. Low-impact exercise
Dr. Theo
5. Mediterranean diet, lots of fruits &
vegetables, anti-oxidants and
Vitamin D
66. Maintain ideal body weight, weight lose
weight if overweight
7. Treat associated depression
8. Use conventional medicine as
necessary
9. Maintain positive attitude/social
support
45
© Jason Theodosakis, M.D. 1996, 2004 47
Curcumin
• Component of Turmeric from root of Curcuma longa plant
• Absorption in humans after oral consumption of unmodified
curcumin extract nil - even at multi-gram doses1-2 • Good 90 day study on 50 subjects3 expanded to 8-month
DBPC OA study with 100 subjects subjects. Used 11,000 000 mg of
phosphatidylcholine bound curcumin4 • When combined with black pepper extract piperine,
bioavailability increased 20-fold, but piperine is a CYP3A4
cytochrome inhibitor – a concern for drug interactions
Dr. Theo
1- Anand p" et al. Mol. Pharmaceutics: 2007, 4(6), pp. 807-818.
2- Marczylo T., et al. Chemother. Pharmacol. 2007, 60, 171·177.
3- Belcaro G., et al. Panminerva Medica: 2010 Giugno; 52 (2 Suppll). 55·62
4- Belcaro G., et al Altern Med Rev. 2010 Dec;15(4):337-44
44
1- Alt. Med Rev. 15:4, pp 337-344
Key Points - Nutraceuticals
• Regarding Glucosamine/Chondroitin… Most of the
null/negative studies to date are so flawed that they
should provide no evidence against efficacy, but are
being used in such a manner anyway
• ASU/Glucosamine/Chondroitin should be co-firstline
pharmacologic therapy for OA
• The quality, dose (potency), label claim accuracy,
biologic activity, and wild claims of dietary
supplement category for OA needs improvement
Dr. Theo
Appendices
48
46
8

Dr. Theo
1
Reading a Label
Ask:
• Are the right ingredients included
in the proper form and amount?
• Is the the amount amount hidden hidden within within a
“proprietary blend?”
• Labeling law requires listing the
ingredients from the highest to
lowest quantity
Does an Oral Cartilage Treatment Work?
The Seven Stages of Evidence
2
3
4
5
6
7
Is it absorbed?
What’s the mechanism of action?
Clinical/Animal symptom y p studies
Clinical/Animal structure studies
Comparison to known treatments
Is it safe?
Long-term outcome measures
ASU - Research Review
Anti-Catabolic, Anti-Inflammatory mechanisms
• Suppresses TNF-a, IL-1b, COX-2, iNOS, PGE2 and NO production in LPS
activated articular chondrocytes and TNF-a, IL-1b in monocyte/macrophages 1
• Inhibits NFk-B, MAPK-14, c-fos and c-jun expression 1
• Suppresses IL-1b stimulation of stromelysin, IL-6, IL-8 and PGE2 in human
articular chondrocytes in culture 2
• Using RA synoviocytes, ASU lowered levels of VGEF (vascular endothelial
growth factor) while increasing levels of TIMP-1 (both p

45
40
35
30
25
20
15
10
5
0
Effect of ASU on NSAID use
and Pain Reduction
# days on NSAIDs VAS Pain
= P < 0.01
N = 260 subjects
Placebo
ASU 300 mg
ASU 600 mg
Appelboom T, Schuermans J, et. al. Symptoms modifying effect of
ASU in knee osteoarthritis. Scan J. Rheumtol. 2001;30:242-7.
55
Where do you draw the line for
acceptable evidence?
Any kind of study of
any quality with any
dosage of any form
of an ingredient, g ,
performed only by
those with direct
personal gain from a
positive outcome
Dr. Theo
Double-blinded,
placebo-controlled
studies, with animal
and basic science
support. Biologic
plausibility and
dosing
Over-Hyped “Science”
Dr. Theo
Multiple, high quality,
DBPC studies, active
comparator trials,
outcome studies and
review articles by
different, independent
reviewers using the
exact same product
in the exact same
population?
57
59
Outcome Data on G/CS
• CS has been shown to reduce NSAID usage by 63-85% in
(11,000) OA patients. Several weeks of CS allowed for an
elimination of about 50% of refill prescriptions for NSAIDs 1
• GS also lowers cost of OA care 2 and decreased need for
Total Knee Replacement 3
• G/CS have shown beneficial f or promising effects ff in most of f
the proposed biochemical targets/pathways in OA: IL-1b,
TNF-a, NF-kB, MMPs, iNOS/NO, PG & HA synthesis,
oxidation, apoptosis, others. 4,5,6
1- Conrozier T. Presse Med 1998 Nov 21;27(36):1866-8 4- Herrero-Beaumont G. Future Rheumatology (2006):1(4);397-414
2- Reginster JY. Arthritis Rheum 2003;48 (9 suppl):89 5- Bali J-P. Sem Arth Rheum. 2001:3(1);58-68 (review)
3- Pavelka K et al, Arthritis Rheum 2004;50,(9 suppl): 251 6- Volpi N. Curr Drug Targets Immune Endocr Metabol Disord. 2004
Jun;4(2):119-27 (review)
Dr. Theo
56
Dr. Theo
Dr. Theo
Common Marketing Ploys
“Fraud Dosing”
• Fraud implies intentional deception for personal
gain for self (or for harm to another)
• Sophisticated, often Doctorate-level formulators
from most large companies know the exact dose
that corresponds with benefit in the research
• Products with a fraction of the efficacious,
researched dose commonly have, or imply claims
and benefits that are not substantiated
58
60
10

Dr. Theo
Dr. Theo
Dr. Theo
“The Non-Inferiority Game”
• Instead of doing multiple double-blinded, placebo
controlled clinical trials…
• Set-up a clinical study between a new agent and a
known, effective agent
• Manipulate the study to favor the new agent by:
– Hand-picking the population to study
– Fidgeting with the dose or form
– Picking inappropriate time intervals
– Being creative with the analysis and statistics used
Deceptive Marketing?
Over-Hyped “Science”
61
• Too short of a duration
• Only 26 patients per
group started
• NNo Pl Placebo b group
• C + Cs has never
performed so poorly in
any other study
• Efficacy vs Effectiveness
63
“The Absorption Game”
• Some marketers try to confuse the public into
believing that absorption relates precisely to
effect
• Often, there’s a significant price premium for a
small increase in absorption
• Absorption helps determine dose, not effect
Dr. Theo 62
Over-Hyped “Science”
Dr. Theo
64
11

Bone
High
Future Approaches to
Cartilage: Growth Factors.
Is that yes or no?
Susan Chubinskaya, PhD
The Ciba-Geigy Professor
of Biochemistry
Sport Fellows Course
Carlsbad, 01-28-2012
The Spectrum of Repair
Potential of Musculoskeletal
Tissues
Muscle Tendon Ligament Meniscus
Cartilage
Sport Fellows Course
Carlsbad, 01-28-2012
Low
•Current US Cartilage Repair
Market value ~60M/1B
•Focal Defects can eventually
lead to OA and Total Knee
Arthroplasty (TKA)
•Cartilage C til regeneration ti
represents an opportunity for
early intervention and
maintenance of an active
lifestyle, delaying or avoiding
TKA
Science drives the ship
Sport Fellows Course
Carlsbad, 01-28-2012
Treatment of Cartilage Injuries: A Medical Need!
Osteochondral
Graft
8%
MicroFracture
20%
Cartilage Repair: US
Procedural Share
ACI
1%
Allografts
1%
Debridment &
Lavage
70%
Still we could not reproduce the native
articular cartilage!
Courtesy of Dr. Cole
Natural History of Cartilage Injury & Repair
Spontaneous Repair Integrative Repair Regeneration
Fails to replicate
normal
structure,
composition and
function
Sport Fellows Course
Carlsbad, 01-28-2012
Fails to repair
interface
between repair
tissue &
cartilage
Does not form
new tissue that
duplicates
structure,
composition &
function
Courtesy of Dr. Hurtig
1

Adult repair tissue tissue-- --Can Can it develop
appropriate properties or…the challenge of
an aging but active patient population!
• But adult repair tissue will adapt slowly
• Regional specialization will be limited
• Need for specialization is greater because
bi biomechanical h i l loads l d will ill be b higher hi h
• Repair tissue will be susceptible to re-injury
Sport Fellows Course
Carlsbad, 01-16-2009
IGFs
Cell proliferation
Chondrogenesis
Images-Dr. A. Shimmin-Melbourne
TGF TGF-β Osteogenesis
(42members) ) Chondrogenesis
BMPs Wound Healing
GDFs/CDMPs BMP BMP-2 2 & 7
EGF
EGF
GGrowth th Factors F t
Proliferation of
Mesenchymal, glial,
and epithelial cells
VEGF
Role in tissue
engineering,
MSC proliferation,
vascular system
repair
TGF TGF-α
Potential role in
normal wound
healing
Slide-Courtesy of Dr. Hurtig
PDGF
Proliferation of
Connective tissue
Glial & Smooth
muscle l cells ll
FGFs, FGF-18 FGF 18
Cell proliferation
Chondrogenesis
Osteogenesis
Sport Fellows Course
Carlsbad, 01-28-2012
Synovial environment
The Diamond Model of
Cartilage Repair
Interactions
Chondrogenic Cells Chondrogenic Scaffolds
Host
Mechanical Environment
Sport Fellows Course
Carlsbad, 01-28-2012
Chondrogenic Cells
Diamond Concept
Host
Bone
Active Agents/Growth Factors
Adapted from Giannoudis et al, 2008, Injury
FGF-18 in cartilage repair/animal study
Intra-articular injection j of FGF18 induced
chondrogenesis and promoted repair of cartilage
lesions in rats with meniscal tear-induced OA. Rats
were subjected to meniscal tear and treatment with
either vehicle alone (a–d) or vehicle containing 5.0 μg
of FGF18 (e–h). (a–d) Black arrows indicate sites of
cartilage damage; red arrows indicate chondrophytes;
green arrow in (a) indicates collapse of the
subchondral bone. (e–h) Black arrowheads indicate
sites of chondrogenesis and repair of cartilage
lesions; red arrows represent chondrophytes.
Sport Fellows Course
Carlsbad, 01-28-2012
2

FGF-18 human trials
Cell therapy with growth
factors
Sport Fellows Course
Carlsbad, 01-28-2012
OP-1/BMP-7 Repair Models
Soft Tissue Models
Ex Vivo Model
•Cartilage Acute trauma/PTOA model
• Joint Tissue Repair
– Articular Cartilage
In Vitro Studies
• Osteochondral Defect
Models
• Chondral Defect Models
• O Osteoarthritis t th iti M Models d l
•Organ/explant cultures (fresh and
allograft cartilage)
•Isolated chondrocytes in
monolayers (primary, ACI)
•Isolated Chondrocytes in Alginate
• Acute trauma/PTOA model
Beads (primary, ACI)
• Clinical data
– Meniscal Cartilage
Hard Tissue Models
– Tendon/Ligament
•Long Bone Defects
• Intervertebral Disc Repair
•Spinal Fusion
•Cranialfacial Defects
– Injurious compression model •Metal Implant Fixation
Sport Fellows Course
Carlsbad, 01-28-2012
Loeser et al A&R
2003
Chubinskaya et al
O&C 2007
•Dentin Regeneration
•Periodontal Defects
Combined growth factor treatment: OP-1 & IGF-1
Primary normal chondrocytes
Alginate
beads
Safranin O
Type II Col
Sport Fellows Course
Carlsbad, 01-28-2012
3

ACI chondrocytes
Chubinskaya et al, 2008 JKS
Sport Fellows Course
Carlsbad, 01-28-2012
•Adult male goats
•14 days follow-up
•histological &
immunohistochemical
analysis
•3.2 mm Ø x 2 mm (deep)
OCD, medial femoral
condyle & trochlea
•Treatment Groups
•100 mg collagen
putty + 250 µg OP-1
•100 mg collagen
putty
•Empty defect
Sport Fellows Course
Carlsbad, 01-28-2012
Osteochondral Defect Model in Goats
(Collaboration with Drs. Oakes and Hurtig)
Day 0 Day 2
Day 3 Day 5 Day 14
Chubinskaya et al, 2004, ICRS
• Adult male dogs
• 6 and 12 weeks follow-up
• Gross and histologic analysis
• Bilateral, 5 mm (diameter) x
5 mm (deep) osteochondral
defects in the medial condyle
• Treatment GGroups
– 100 mg OP-1 collagen putty
(250 µg OP-1)
– 100 mg collagen putty
Untreated
(Collagen
Putty)
– Empty defect
Sport Fellows Course
Carlsbad, 01-28-2012
Cook et al. JBJS 2003, 85-
A(Suppl 3):116-123
Osteochondral Defect Model
OP-1
6 Weeks 12 Weeks
Summary
•No ossification in
any joint;
•Significant
enhancement of both
cartilage and bone
repair in the defects;
•Less fibrocartilage
and an increase in
hyaline cartilage.
Day 0
Placebo Control
Staining with pro-OP-1 antibody
Day 14
LMC LTP LMC LTP
Sport Fellows Course
Carlsbad, 01-15-2011
4

Mature OP OP-1 1
staining
• rhOP-1 remains within collagen
vehicle for two weeks;
• healing and bridging of the defect is
initiated by day 5;
• activation of endogenous OP-1;
14 days post op + OP-1
Chubinskaya et al, 2004, ICRS
Pro-OP-1 staining
• Autocrine and rhOP-1 contribute to
the repair process suggesting that
both have to be considered for growth
Sport factors Fellows therapy Course
Carlsbad, 01-16-2009 RMC LTP RTP
Mosaicplasty Augmentation
Autograft Plug Control at 12 weeks
Autograft Plug with OP-1 Putty at 12 weeks
OP-1 augments both cartilage and bone integration in mosaicplasty
Sport Fellows Course
Carlsbad, 01-28-2012
• 9 adult sheep
• 3,6 and 12 weeks follow-up
• Bilateral model, two osteochondral
defects in each medial femoral
condyle
• Donor site (5.5 mm x 10 mm) and
mosaicplasty plug recipient site (5.4
mm x 10 mm) on each condyle
• Treatment groups
– Donor hole filled with 75 mg OP-1
collagen putty (200 µg OP-1)
– Donor hole left empty
– Recipient hole with mosaicplasty
plug augmented with 75 mg OP-1
collagen putty (200 µg OP-1)
– Recipient hole with mosaicplasty
plug only
Sport Fellows Course
Carlsbad, 01-28-2012
Shimmin et al. Trans ICRS 4 th
Symposium, No. 16, 2002, Toronto
• Experimental Procedure 24
sheep (1year old, 60 kg)
• Knee 10 mm chondral
defects
– Trochlea
– Condyle
• Continuous 2 week OP-1
delivery via mini-osmotic
mini osmotic
pumps
• Doses: 0, 55 μg and 170
μg
• Arthroscopic monitoring of
repair
• Sacrifice at 3 and 6 months
Jelic et al (2001) Growth
Factors 19:101-113
Sport Fellows Course
Carlsbad, 01-28-2012
Sheep Mosaicplasty
Augmentation Study
Mosaicplasty Augmentation
Donor Holes-Histology at 12 weeks
Untreated
OP-1 Treated
Chondral Defect Repair: OP-1 Sheep Model
Histology, 6 mo
Buffer Treated
OP-1 Treated Summary:
•Significant g cartilage g repair p
was observed with OP-1
delivered into the joint fluid;
•No cartilage repair was
observed in control defects
without OP-1;
•New cartilage is filled with
chondrocytes embedded into
Type II collagen;
•New cartilage was well
bonded with the old
cartilage.
5

Rabbit ACLT model: Protective effect of OP-1
on cartilage in the development of OA
Badlani et al, 2008 OA&C
India Ink
Hayashi et al. Arth Res & Ther 2008
Mini-osmotic pump delivery
Injections of 5% lactose-buffered
rhBMP-7 in PBS. Sport Fellows Course
Carlsbad, 01-28-2012
OP-1 PREVENTS DEGENERATIVE CHANGES IN A
CONTUSSIVE IMPACT MODEL OF OA IN SHEEP
Mark Hurtig, Susan Chubinskaya, Jim Dickey, David Rueger
Is OP-1 as a Osteoarthritis-Modifying Peptide?
Time=0 bilateral impact injuries (30 MPa, 6mm diameter x2 )
Time=0 Vehicle control OP-1 Implant injection (340 µg) i.a. injection
Time=1 week Vehicle control OP-1 Implant injection (340 µg) i.a injection
Time=12 weeks Sacrifice
Results: Results
OP OP-1 suppressed leukocyte influx in acute phase
OP OP-1 preserved sGAG content of cartilage
OP OP-1 improved (P< (P

India ink stained area for the medial femoral condyle
Group A Group B Group C
OP-1 Vehicle OP-1 Vehicle OP-1 Vehicle
Mean 11.1 44.8 15.7 30.0 30.0 28.0
T-test p

μCT of impacted cartilage explants
Histology Safranin O staining
Disc degeneration model
Untreated cntr Compressed disc ROP-1
Sport Fellows Course
Carlsbad, 01-28-2012
Sham COP-1
Chubinskaya et al, JOR 2007
Kawakami et al, 2005; 2007
Bajaj et al, ORS
2011
Attenuation levels
at varying depths.
• OP-1 injection induces:
• anabolic
– restoration of the
ECM;
– stimulation of OP-1
synthesis;
• anti-catabolic effects
– downregulates:
• Aggrecanase
• Substance P
• MMP-13
• Interleukin-1β
• TNF-α
Degenerative disc with annular tear
or Contained herniated disc
Intervertebral Disc Degeneration Models
The compressed NP
OP OP-1 OP OP-1 1 injection injection Insertion of 0.8 mm K-wire
Sport Fellows Course
Carlsbad, 01-28-2012
Spring
HUMAN EXPERIENCE WITH INTRA-
ARTICULAR OP-1
more than 50 cases, up to 10 years follow up
Example: 41 yo football player
TIRM, Regensburg, November 2010
Osteochondral fragment retrieved from the joint space
Courtesy of Dr. Shimmin
8

OP-1 OP 1 putty was placed beneath the defect
12 MONTH ARTHROSCOPY
•OP-1 has not done any harm;
•Assisted fixation of the
fragment;
•Improved integration of the
fragment to the surrounding
normal cartilage
Overall Conclusions
• Application of a single growth factor or a combination
of those is a promising approach in cartilage repair
• OP-1 is definitely one of the best candidates so far
for cartilage repair and showed similar efficacy in
various in vivo and ex vivo models, both animal and
human cartilage
• Traditional approaches pp ( (allograft, g , autograft, g , ACI) )
might be optimized by addition of growth factors
• Combination of growth factors and other anticatabolic
agents of various mode of action has a
potential in cartilage repair
• Activation of autocrine anabolic pathways has to be
taken in consideration in designing growth factor
therapy.
Sport Fellows Course
Carlsbad, 01-28-2012
Therapeutic Application of OP-1
Clinical Studies
• Phase 1, double-blind, randomized, multicenter, placebo-controlled,
single-dose escalation safety study in patients with knee OA
OARSI responder criteria
•All subjects completed the study
•OP-1 groups had more responders
with OARSI criteria than placebo
Sport Fellows Course
Carlsbad, 01-28-2012
A trend toward greater
symptomatic improvement
than placebo
A higher frequency of
injection site pain
Hunter et al, 2010
Challenges of Growth Factors Therapy
• Which one or which ones?
• Alone or in combination with other agents of a
different mode of action
• Formulations
• Scaffolds/Carriers
• DDoses
• Treatment regimes
• Delivery methods: local vs systemic vs gene
• Time of Intervention
• Possible adverse effects
Sport Fellows Course
Carlsbad, 01-28-2012
9

Charities
giftofhope
Organ&Tissue
Donor Network
TIRM, Regensburg, November Donor’s 2010Families
Collaborators:
Rueger D
Hurtig M
Kildey R
Cole B
Wimmer M
Oegema T
Oakes B
Loeser R
Chubinskaya’s
Chubinskaya s
lab:
Lidder S
Pascual Garrido C
Hakimiyan A
Rappoport L
Yanke A
Segalite D
Stryker Biotech
Bajaj S
Kirk S
Ruta D
Ciba-Geigy Endowed Chair Meininger A
Drs. Cole and Galante Research
Funding
10

Hip the New Frontier: Cartilage and Labral Considerations
International Sports Medicine Fellowship Course
Carlsbad, CA
2012
Michael Gerhardt, MD
Santa Monica Orthopaedic and Sports Medicine Foundation
2020 Santa Monica Blvd, 4 th Floor
Santa Monica, CA 90404
mgerhardt@smog-ortho.net
I. Current Indications for Hip Arthroscopy (1)
a. FAI – accounts for majority of arthroscopic procedures today
i. Labral debridement/repair
ii. Chondroplasty
iii. Osteoplasty – femoroplasty and acetabuloplasty
b. Ligamentum teres injuries (2)
c. Snapping Hip (3-4)
i. Internal
1. Snapping Iliopsoas tendon
ii. External
1. Snapping iliotibial band
2. Snapping glut max
d. Loose Bodies
e. Synovial disease
f. Peritrochanteric disorders (5, 6)
i. Trochanteric bursitis
ii. Abductor injuries of the hip
g. Instability (7)
h. Joint Sepsis
i. Early OA?
j. List is expanding rapidly
i. Subgluteal syndrome (8,9)
ii. Proximal Hamstring tendon injuries
iii. Osteitis pubis?
II. Labral Injuries – Beyond FAI
a. Function of the Labrum
i. Maintains continual contact on femoral head
ii. Augments stability of the joint (10,11)
1. Provides suction seal of femoracetabular joint

2. Maintains negative intrarticular pressure – resists
distractive forces
iii. Disperses Contact stress during weight bearing
iv. Synovial fluid distribution
v. Proprioceptive function
b. Management options for labral injuries (12)
i. Debridement (13, 16)
ii. Labral Repair (14)
1. Primary repair of labral tears
a. Only 4% labral tears amenable to primary repair
(Gerhardt, 2010)
b. Majority of “labral repair” is actually LABRAL
REFIXATION
iii. Labral Reconstruction (15-16)
1. Theory
a. Labrum plays critical role in normal mechanics
of hip
b. Labral deficiency leads to internal derangement
i. Microinstability
ii. Abnormal mechanics of femoroacetabular
joint
iii. Joint preservation depends on labral
integrity
2. Indications
a. Segmental labral deficiency
b. Minimal existing chondral damage
c. Favorable biological and mechanical
environment
3. Clinical studies
a. Literature review
4. Options
a. Autograft
i. Iliotibial band
ii. Gracilis (distal)
iii. Ligamentum teres
b. Allograft
i. Soft tissue donor sites – Hamstring, post
tib, etc
c. Bioscaffolds?
III. Chondral Injuries (16-19)
a. Femoral Head Lesions
i. Types of FH chondral injuries
1. Primary chondral injury
2. Osteochondritis Dessicans (OCD) - rare
3. Lateral Impact Syndrome (20)
4. AVN?

REFERENCES
ii. Management of FH chondral injuries
1. Microfracture
2. Repair?
3. Resurfacing
a. Biologic options
b. Arthroplasty options
b. Acetabular Lesions
i. Types of Acetabular chondral injuries
1. Primary articular cartilage injury
2. Osteochondritis Dessicans (OCD) – very rare!
ii. Management options of acetabular chondral injuries (21-22)
1. Microfracture
2. Repair of “delamination” injuries
a. Suture repair (23)
b. Fibrin Glue augmentation (24)
c. Resection and microfracture (25-26)
d. Microfracture and repair of cartilage flap
3. Resurfacing options (27)
a. ACI
b. Scaffolds
c. OATS
4. Arthroplasty
a. Options
i. Partial – Hemi caps
ii. Hip Resurfacing
iii. Total Hip Replacement
1. Stevens MS, Legay DA, Glazebrook MA, Amirault D. The Evidence for hip
arthroscopy: grading the current indications. Arthroscopy. 2010 Oct;26(10):1370-83
2. Byrd JW, Jones, KS. Traumatic rupture of the ligamentum teres as a source of hip
pain. Arthroscopy. 2004 Apr;20(4):385-91.
3. Ilizaturri VM, Chaidez C, Villegas P, Briseno A, Camacho-Galindo J. Prospective
randomized study of 2 different techniques for endoscopic iliopsoas tendon release in the
treatment of internal snapping hip syndrome. Arthroscopy. 2009 Feb;25(2):159-63. Epub
2008 Oct 10.

4. Voos JE, Rudzki JR, Shindle MK, Martin H, Kelly BT. Arthroscopic anatomy and
surgical techniques for peritrochanteric space disorders in the hip. Arthroscopy. 2007
Nov;23(11):1246.e1-5.
5 Voos JE, Shindle MK, Pruett A, Asnis PD, Kelly BT, Endoscopic Repair of Gluteus
Medius Tendon Tears of the Hip.Am J Sports Med. 2009 Feb 9.
6 Robertson WJ, Gardner MJ, Barker JU, Boraiah S, Lorich DG, Kelly BT. Anatomy and
dimensions of the gluteus medius tendon insertion. Arthroscopy. Feb;24(2):130-6, 2008.
7. Phillippon MJ, Kuppersmith DA, Wolff AB, Briggs KK. Arthroscopic findings
following traumatic hip dislocation in 14 professional athletes. Arthroscopy. 2009
Feb;25(2):169-74.
8. Martin H, Shears S, Palmer I. Evaluation of the Hip. Sports Medicine & Arthroscopy
Review: June 2010;18(2):63-75
9. Martin H. The Endoscopic treatment of sciatic nerve entrapment/deep gluteal
syndrome. Presented at ISHA 2010 Oct 8.
10. Ferguson SJ, Bryant JT, Ganz R, Ito K. The influence of the acetabular labrum on
hip joint cartilage consolidation: a poroelastic finite element model. Journal of
Biomechanics. 2000 Aug;33(8):953-60.
11. Ferguson SJ, Bryant JT, Ganz R, Ito K. An invitro investigation of the acetabular
labral seal in hip joint mechanics. Journal of Biomechanics. 2003;36:171-8.
12. Kelly BT, Weiland DE, Schenker ML, Philippon MJ. Arthroscopic labral repair in the
hip: surgical technique and review of the literature. Arthroscopy. 2006;21:1496-504.
13. Santori N, Villar RN. Acetabular labral tears: result of arthroscopic partial
limbectomy. Arthroscopy. 2000 Jan-Feb;16(1):11-15
14. Larson CM, Giveans MR. Arthroscopic debridement versus refixation of the
acetabular labrum associated with femoroacetabular impingement. Arthroscopy 2009
Apr;25(4):369-76.
15. Phillipon MJ, Briggs KK, Hay CJ, Kuppersmith DA, Dewing CB, Huang MJ.
Arthroscopic labral reconstruction in the hip using iliotibial band autograft: technique and
early outcomes. Arthroscopy 2010 Jun;26(6):750-6.
16. Byrd JW, Jones KS. Hip arthroscopy for labral pathology: prospective analysis with
10-year follow-up. Arthroscopy. 2009 Apr;25(4):365-8.
17. Byrd JW, Jones KS. Prospective analysis of hip arthroscopy with 10-year followup.
CORR. 2010 Mar;468(3):741-6.

18. Philippon MJ, Schenker M, Briggs K, Kuppersmith D. Femoroacetabular
impingement in 45 professional athletes: associated pathologies and return to sport
following arthroscopic decompression. Knee Surgery Sports Traumatology Arthroscopy.
2007 Jul;15(7):908-14.
19. Singh PJ, O’Donnell JM. The outcome of hip arthroscopy in Australian football
league players: a review of 27 hips. Arthroscopy. 2010 Jun;26(6):743-9.
20. Byrd JW. Lateral impact injury: A source of hip pathology. Clin Sports Med. 2001
Oct;20(4):801-15.
21. Beaule PE, O’Neill M, Rakhra. Acetabular labral tears. JBJS 2009 Mar 1;91(3):701-
10.
22. Gdalvitch M, Smith K, Tanzer M. Delamination cysts: a predictor of acetabular
cartilage delamination in hips with a labral tear. CORR. 2009 Apr;467(4):985-91.
23. Sekiya JK, Martin RL, Lesniak BP. Arthroscopic Repair of Delaminated Acetabular
Articular Cartilage in Femoroacetabular Impingement. Orthopedics. September
2009;32(9):692.
24. Tzaveas AP, Villar RN. Arthroscopic repair of acetabular chondral delamination
with fibrin adhesive. Hip International. 2010 Jan-Mar;20(1):115-9.
25. Philippon MJ, Schenker ML, Briggs KK, Maxwell RB. Can microfracture produce
repair tissue in acetabular chondral defects? Arthroscopy. 2008 Jan;24(1):46-50.
26. Crawford K, Philippon MJ, Sekiya JK, Rodkey WG, Steadman JR. Microfracture of
the hip in athletes. Clin Sports Med. 2006 Apr;25(2):327-35
27. Ellander P, Minas T. Autologous Chondrocyte Implantation in the hip: Case report
and technique. Operative Techniques in Sports Medicine. 2008 Oct;16(4)201-6

12th International Sports Medicine Fellows Conference
Comprehensive approaches to articular cartilage repair and hip arthroscopy
Carlsbad, CA January 27-29, 2012
Product Challenges for Partial Thickness Articular Cartilage Treatment
Wayne K. Augé II, MD
Department of Research and Development
NuOrtho Surgical, Inc. at the
Advanced Technology & Manufacturing Center
University of Massachusetts Dartmouth
This presentation will focus on the treatment of partial thickness articular cartilage lesions with
an emphasis on the challenges these lesions create for therapeutic product development.
Traditionally, surgical intervention has been limited to palliative tissue removal because of
volumetric and functional over-resection that enlarge lesion size and eliminate surrounding
healing phenotypes. Viewing partial-thickness lesions as a wound healing problem has enabled
new therapeutic approaches which have been designed to decrease the disease burden associated
with these lesions.

Reimbursement and Coding
Issues for Articular
Cartilage Treatment
Ralph A. Gambardella, M.D.
Kerlan Kerlan-Jobe Jobe Ortho Clinic
Carlsbad Cartilage Course 2011
Linking Industry Practices
and Technologies
Experience gained
from engagements
with other
Orthopaedic
practices,
Ambulatory Surgery
Centers, and
Hospitals
How do we identify pilot opportunities?
Potential
Pilots for the
COE
Internal J&J Competencies
COE Outputs
•Strategic Partnerships with Technology Vendors
•Research papers with repeatable findings for Alumni
Ideas and
concepts gained
from knowledge
partners
(Gartner) and
participation in
industry
technology
summits
Business Center of
Excellence (COE) Concept
The Business COE provides a
mechanism for experimenting p gwith
business concepts and technology to
evaluate the potential for improving the
performance of Orthopaedic practices
SUGICAL
REIMBURSEMENT
� Accounts Receivable Duration
– Driven by y ‘controllable’ activities
� Creating appropriate coding supported by
appropriate documentation
� Time between surgery and submission of a ‘clean
claim’
– Driven by ‘uncontrollable’ activities
� Time between submission of ‘clean claim’ and
receipt of reimbursement
1

TOTALCHART
TECHNOLOGY
A SURGEON’S SURGEON S PARTNER
Enhance accuracy
Enhance Reimbursement
Pilot Timing and Metrics
The cycle time data utilized in this presentation was
captured for Dr. Gambardella during three distinct
periods:
Pilot Purpose
The technology introduced in this study enables
the surgeon to code and dictate via a handheld
device and includes coding logic to ensure the
appropriate use of codes and modifiers modifiers.
This analysis focused on two questions:
1. Will the introduction of the handheld device
impact administrative cycle times?
2. Will these cycle times change as a surgeon
becomes more familiar with the technology?
Summary of Findings – Faster
Claim Submission
Duration between surgery and claim submission
� Manual: 9.9 Days
� Technology enabled: 7.4 Days (a 25% reduction)
Percent of claims submitted with 10 days
� Manual: 72.0%
� Technology enabled: 86.6% (a 20%
improvement)
Percent of claims submitted within one week
� Manual: 49.5%
� Technology enabled: 81.8% (a 65%
improvement)
2

Summary of Findings – Faster
Claim Submission
Duration between surgery and claim submission
� Manual: 21.2 Days
� Technology enabled: 14.0 Days (a 34%
reduction)
Percent of claims submitted with 10 days
� Manual: 59.2%
� Technology enabled: 70.8% (a 12%
improvement)
Percent of claims submitted within one week
� Manual: 32.7%
� Technology enabled: 50.8% (a 80%
improvement)
Summary of Findings – Faster
Reimbursement
Duration between claim submission and
reimbursement
� Manual: 51.2 Days
� Technology enabled: 32.5 Days (a 36%
reduction)
Percent of reimbursements received within 40
days
� Manual: 40.8%
� Technology enabled: 63.1% (a 36%
improvement)
Summary of Findings – Faster
Reimbursement
Duration between claim submission and
reimbursement
� Manual: 62.8 Days
� Technology enabled: 43.7 Days (a 30%
reduction)
Percent of reimbursements received within 40
days
� Manual: 44.1%
� Technology enabled: 49.2% (a 11%
improvement)
Summary of Findings – Fewer
Past Due Accounts
Percentage of claims with reimbursement
cycle > 90 days
�� Manual: 31.2% 31 2%
� Technology enabled: 14.4% (a 54%
reduction)
3

Summary of Findings – Fewer
Past Due Accounts
Percentage of claims with reimbursement
cycle > 90 days
�� Manual: 30.6% 30 6%
� Technology enabled: 18.5% (a 45%
reduction)
ARTICULAR CARTILAGE
SURGICAL CODES
� CPT 29886 OCD drill intact lesion
� CPT 29887 OCD intact lesion with internal
fixation
� CPT 29885 OCD with bone graft with or
without internal fixation
ARTICULAR CARTILAGE
SURGICAL CODES
� CPT 29877 Chondroplasty/Debridement
� CPT 29874 Removal of Loose Body
� CPT 29879 Microfracture
� CPT 29866 Arthroscopic Osteochondral Autograft
� CPT 29867 Arthroscopic Osteochondral Allograft
� CPT 27415 Open Osteochondral Allograft
� CPT 27416 Open Osteochonral Autograft
� CPT 29870 Genzyme Chondrocyte Biopsy
ARTICULAR CARTILAGE
SURGICAL CODES
� CPT 27412 Autologous Chondrocyte
Implantation
�� CPT 29868 Meniscal Transplantation
� CPT 27457 Osteotomy after epiphyseal
closure
� CPT 27418 Anterior Tibial Tubercleplasty
� CPT 29870 Arthroscopy with biopsy
4

ARTICULAR CARTILAGE
SURGICAL CODES
� CPT 27442 Arthrosurface Trochlea
� CPT 27438 Arthrosurface Patella
�� CPT 27446 Unicompartmental Knee
ARTICULAR CARTILAGE
CODES
� Modifiers
59 is used to identify a distinct procedural service
Separate p incision or lesion
Separate compartment
Separate injury
22 is for extraordinary situation ( ie,obesity)
Must document with cover letter
ARTICULAR CARTILAGE
ICD ICD-9 9 CODES
� 717.9 Unspecified internal derangement
� 719.96 Unspecified disorder of joint
�� 732 732.7 7 Osteochonditis Dissecans
� 733.90 Disorder of bone and cartilage
� 733.92 Chondromalacia
� 836.0 Tear medial meniscus
� 836.1 Tear lateral meniscus
ARTICULAR CARTILAGE
REIMBURSEMENT
� Hospital or Surgicenter Problems
– Gl Global b l CContract t t ffor services i
�Differs for different payors
�Differs for different geographic
areas
5

ARTICULAR CARTILAGE
REIMBURSEMENT
� Surgical Implant and Disposable Costs
– Shaver ( $40-100 )
– RF Device ( $112-185 )
– Osteochondral autograft kit ( $380-618 )
– Osteochondral OBI kit ($225 )
– Osteochondral allograft kit (Rental)
– Chondral pins/screws ( $695 )
– Meniscal repair implants ( $95-220 )
ARTICULAR CARTILAGE
REIMBURSEMENT
� DME’s
– Braces
– Cold Therapy
– Pain pumps
� Viscosupplementation
� Medications
� Physical Therapy
ARTICULAR CARTILAGE
REIMBURSEMENT
� IMPLANT MATERIALS
� Osteochondral allografts ($9,950)
� OBI Plugs ($500)
� Meniscal allografts ($4,750)
� ACL allografts ($2,500)
� Osteotomy implants ($795)
� Cell implants
– Carticel ($20,000)
� OP-1
CASE 1
� Chondroplasty Patella $400
� MFC defect (3.0cm) $1,500
�� Meniscal Repair $440
� ACL Allograft $2,500 & $500
TOTAL $6,340
6

CASE 2
� Chondroplasty Patella $400
� ACI MFC $20,000
�� Meniscal Transplant $4,750 $4 750 & $1100
� ACL Allograft $2500 & $500
TOTAL $29,250
CONCLUSIONS
� Get involved early in your career with the
business end of what you do
� Be a leader and embrace industry as your
� Be a leader and embrace industry as your
partner to help improve your practice and
improve your patients outcomes
CONCLUSIONS
Impact to Overall A/R Cycle
�RAG : 30% improvement
– 72.8 days Manual
– 51 51.2 2 d days w/Tech /T h
�JTD : 35.8% improvement
– 72.5 days Manual
– 46.5 days w/Tech
7

General Criteria
for
Cartilage Repair
� Age 15-50 years
�� Di Disabling bli llocalized li d kknee pain i ffor six i months th
which has failed conservative treatment
� An intact meniscus is present
� Lesion must be discrete, single and unipolar
� Lesion is largely contained with near normal
surrounding cartilage (Gr 0,1,2)
General Criteria
for
Cartilage Repair
�� No history of cancer in bones fat or
muscle of affected limb
� Body Mass Index (BMI) of < or = to
30
General Criteria
for
Cartilage Repair
� A normal joint space is present
� No active infection
� No osteoarthritis or inflammation
� Knee is stable with normal mechanical
alignment
� Patient can comply with post-operative
restrictions for wt. bearing
ACI Criteria
� Inadequate response to prior surgery
� Defect size 1.5-10cm sq
�� Cartilage only defect
� No allergy to gentamicin
� Focal, full thickness isolated to
MFC,LFC trochlea
� Defect from acute or repetitive trauma
� ALL General Criteria met
8

Osteochondral
Autograft Criteria
� Arthroscopic examination
� Defect size between 1.0 to 2.5cm sq
� Focal, full thickness isolated to
MFC,LFC or trochlea
� Defect from acute or repetitive
trauma
� ALL General Criteria met
Investigational
Procedures
� ALL procedures on joints other than
the knee
� ANY procedure d th that t ddoes not t meet t
ALL of the criteria
� ALL use of non-autologous synthetic
bone filler materials
� ALL use of minced cartilage
Osteochondral
Allograft Criteria
� Arthroscopic examination
�� Defect size = or > 22.0cm 0cm sq
� Focal, full thickness isolated to
MFC,LFC or trochlea
� Defect from acute or repetitive
trauma
� ALL General Criteria met
9

12 th International Sports Medicine Fellows Conference
January 27-29, 2012● Carlsbad, California
7:30 AM - 7:35 AM Introduction
Session IV: Hip Arthroscopy
7:35 AM - 7:45 AM The Basics - Indications Michael Gerhardt, MD USA
7:45 AM - 8:00 AM
8:00 AM - 8:15 AM
8:15 AM - 8:30 AM
How To Get Started - Patient Assessment, Treatment
Algorithm
ABC's in the OR - Patient Set-Up, Positioning, Central and
Peripheral Compartment Access and Portal Placement
FAI - Making the Diagnosis, Imaging, Management and
Surgical Treatment
Warren Kramer, MD USA
J.W. Thomas Byrd, MD USA
Mark Safran, MD USA
8:30 AM - 8:40 AM Sports Hernia – Diagnosis, Algorithm and Surgical Treatment William Hutchinson, MD USA
8:40 AM - 8:55 AM
8:55 AM - 9:10 AM
Case Presentation - Hip and Groin Injury in the Professional
Athlete
Hip Arthroscopy - Where Have We Been, Where Are We Now
and Where Are We Going?
Michael Gerhardt, MD USA,
Mark Safran, MD USA,
Warren Kramer, MD USA
J.W. Thomas Byrd, MD USA

INTERNATIONAL SPORTS
MEDICINE FELLOWSHIP
SYMPOSIUM 2012
Michael B. Gerhardt, MD
Intrarticular Hip Disorders
�� Commonly misdiagnosed
�� Traditionally athletes told “live with it”
�� Hip Arthroscopy now offers a
minimally invasive treatment option !
Assessment
Assessment
Is the problem truly
the hip joint???
Confounding disorders
• Sports hernia/
hernia/
Pubalgia
• Lumbar disease
• Extrarticular
disorders:
bursitis, tendonitis,
etc
INDICATIONS
Overview of Common
Hip p Injuries j
Michael B. Gerhardt, MD
Team Physician, LA Galaxy and Chivas USA
Team Physician, US Soccer
Assessment
Presentation
�� History of trauma variable
�� Mechanical symptoms common
�� Exacerbating features
1

Favorable Prognostic Indicators
�� History of significant traumatic event
�� Mechanical symptoms
• Intermittent pain/catching
• Sharp or stabbing pain
Current Indications
“The “The big big 3” 3”
�� Labral Pathology
�� Chondral Damage
�� FAI
Current Current Indications
Indications
�� Ligamentum teres rupture
�� Loose Bodies
�� Degenerative Arthritis?
SALT Lesion
Lesion
(Superior Acetab Labral Tear)
Common Lesions of the Hip
Recently…
indications have
expanded…
and the list is
growing rapidly!
Current Current Indications
Indications
�� Synovial disease / Rheumatologic
�� Joint sepsis
2

Current Current Indications
Indications
Capsular laxity / Instability
-Microinstability
Microinstability
-Macroinstability
Macroinstabilityy
Current Current Indications
Indications
The Peritrochanteric Space
�� Trochanteric bursitis
�� Snapping IT band
• The The External External Snapper Snapper
�� Abductor tears – Glut Medius Tears
“Rotator “Rotator Cuff Cuff Tears Tears of of the the Hip” Hip”
Most Common Lesions of the Hip
�� Labral Pathology
�� Articular cartilage injury
�� Femoroacetabular Impingement (FAI)
�� Ligamentum teres rupture
�� Degenerative disease
Current Current Indications
Indications
�� Diagnostic – Unresolved hip pain
�� �� AVN?
AVN?
�� Snapping hip
• Internal snapper – ILIOPSOAS TENDON
Relative Relative Contraindications Contraindications to to
Hip Hip Arthroscopy
Arthroscopy
�� Severe degenerative arthritis
�� Stress Riser – impending fracture
�� Severe obesity
Labral Labral pathology pathology
Etiology
• Most common injury in athletes
• Twisting mechanism common
�� Certain sports pre-dispose
pre dispose
• Macrotrauma ( (tackle tackle) ) vs. Microtrauma
(FAI FAI)
3

Labral Labral pathology pathology
Natural History
• Unknown
• Do labral tears heal?
Labral Labral pathology pathology
�� �� Uncertain
Uncertain
�� Some patients improve with conservative
treatment
Arthroscopic Treatment
• Labral debridement vs repair???
�� �� Labral tissue contains important nociceptive
and neural mechanoreceptors critical to joint
�� Johnson Johnson & & Gerhardt, Gerhardt, 2010 2010
Labral Repair Technique
Hip Specific
Implants,
Instrumentation
and Techniques
rapidly improving!
Cinch Stitch for PushLock use in the hip
Labral Labral pathology pathology
Arthroscopic Treatment
• Goal of surgery
Labral Labral pathology pathology
�� Resect or repair damaged tissue
�� Create stable transition zone at labral-
cartilage junction
�� Preserve as much normal tissue as possible
Arthroscopic Treatment
•Labral Labral debridement vs repair repair???
???
�� Repair is possible and preferable
�� �� Most lesions not repairable
�� Awaiting studies to assess success of
repaired labrum
�� Repair is critical if acetabular pincer lesion
resected
Will discuss controversies later in meeting!
PEEK and Bio-Pushlock
Bio Pushlock
�� Hip specific push-
locks
(2.9 mm Bio,
PEEK, , or
Biocomposite)
�� Pretension repair
�� Knotless Option
�� Good fixation!
4

SutureTaks w/ FiberWire
Bio, PEEK, or
Biocomposite
SutureTaks with
FiberWire
Cinch Stitch Repair
Labral Base refixation Labral Base refixation
Labral Base refixation
Chondral Chondral Injuries Injuries
�� Articular cartilage injuries can be
devastating!
�� Worst W WWorst t prognosis i
�� MRI/MRA low sensitivity
• Often Often not not diagnosed diagnosed until until arthroscopy
arthroscopy
5

Chondral Chondral Injuries Injuries
Common locations
• Femoral head – less common
less common
�� Lateral impact syndrome
• Anterolateral acetabulum
�� Common in impingement syndrome
Chondral Chondral Injuries Injuries
Lateral Impact Syndrome (Byrd, 2001)
• Usually contact sports
• Athlete lands directly on lateral hip
�� �� Violent contact between femoral head and
acetabulum
�� Shear Shear force force creates creates medial medial femoral femoral head head
articular articular cartilage cartilage injury! injury!
Lateral Impact Syndrome Lateral Impact Syndrome
Lateral Impact Syndrome
Chondral Chondral Injuries Injuries
Treatment
• Debridement/chondroplasty
• Microfracture
�� Promising results acetabular defects (Byrd, 2006)
• Resurfacing?
R RResurfacing? f i ?
�� Biologic – ACI?
�� Non Non-biologic biologic
• Arthrosurface?
• Resurfacing Arthroplasties?
• THR?
6

Femoroacetabular Impingement
(FAI)
PINCER TYPE CAM TYPE
Arthroscopic Rim
Trim
Ligamentum Ligamentum Teres Teres Injury Injury
Ligamentum Ligamentum Teres Teres Injury Injury
Acute tear
Arthroscopic treatment
• Debridement
Femoroplasty
�� Excellent results reported
�� �� 96% improvement rate (Byrd 2004)
• Repair – case report (Philippon, 2001)
�� NOT recommended!
Ligamentum Teres Injury
�� Athletes can have acute tear
�� Mechanism
Mechanism
• Twisting/rotating
�� Symptoms
• Vague, non specific groin pain
•+/ +/- mechanical complaints
�� Difficult diagnosis
• Often not confirmed until arthroscopy
Ligamentum Ligamentum Teres Teres Injury Injury
Chronic tear
Loose Bodies
Clearest indication for hip arthroscopy
• Important for future integrity of joint
• Arthroscopic removal superior to open
procedure
7

Loose Loose Bodies Bodies
�� Symptoms
• Catching, locking, giving way
�� Diagnosis
• S Sometimes ti evident id t on plain l i xrays
•MRI MRI
• CT scan excellent for subtle
osteochondral frags
THANK YOU!
Thank You!
Loose Loose Bodies Bodies
�� Always look in peripheral
compartment!!
�� Central compartment only allows
ACCESS TO ~70% of the joint
• Gerhardt, AAOS, 2006
8

Case Report
Warren G. Kramer III, MD
� 23 year old female professional surfer with bilateral hip
pain.
� No specific injury but pain is made worse with surfing.
patient complains of popping sensation in the groin.
� Exam: +FAIR/FABER. +Pain with resisted straight leg raise
(internal and external rotation).
� Failed conservative care (PT, NSAIDs, Rest).
� MRI and xrays were taken.
� Labral tear
Hip Injuries From Surfing
� Pain secondary to FAI‐ CAM or PINCER Type
� Snapping Psoas Tendon and/or Tendonitis
� Proximal Hamstring Tear
� Rectus Femoris Tear
� Ligamentum Teres Tear
� Avulsion of ASIS tensor Fascia Lata Sartorius
� Sports Hernia
� Trochanteric Bursitis
� Osteitis Pubis
� ericah.MOV
Things to look out for…
Clear Cell Chondrosarcoma
Center Edge Angle 37 degrees (right hip)
Center Edge Angle 40 degrees (left hip)
1/23/2012
1

Alpha Angle 95 degrees (right hip)
Alpha Angle 95 degrees (left hip)
(Subtle Anterior Prominence)
Surgical photos of right hip
with evidence of FAI and
s/p osteoplasty
Surgical photos of left hip
with evidence of FAI and
s/p osteoplasty
MRI Left Hip
(Labrum appears normal despite
significant pain/limitation)
MRI Left Hip
(Labrum appears normal despite
significant pain/limitation)
Patient did well post op for 5 months but had
recurrence of left hip groin pain…
� NSAIDs were given, repeat MRI (possible labral re‐tear), U/S
guided cortisone injection into the joint and psoas bursa
� Patient reported some relief with intra‐articular joint/psoas
bursa but continued to have pain that kept her from surfing.
Surgical photos of right hip
with labral tear and repair
Surgical photos of left hip
with labral tear and repair
Surgical photos of left hip showing intact labral repair and
thickened, yellow degeneration of psoas tendon
1/23/2012
2

Patient is 3 months post op and has
returned to surfing without pain.
� Pain after hip arthroscopy is not uncommon.
� Is a psoas tendon release under or over utilized?
� Does repairing the labrum or capsular release near the
psoas cause adhesions around the psoas tendon?
� Why would a 23 year old female have yellowish
degeneration in her psoas tendon?
Gracias!
1/23/2012
3

ABC's in the OR - Patient Set-Up, Positioning,
Central and Peripheral Compartment Access and Portal Placement
J. W. Thomas Byrd, M.D.
info@nsmfoundation.org
12th International Sports Medicine Fellows Conference
Carlsbad, California
January 29, 2012
I. Equipment
A. Fracture table
- Tensiometer for monitoring traction forces intraoperatively is the most
important modification
B. C-arm image intensifier
C. 70 and 30 video-articulated arthroscopes
D. Fluid management system
E. Specialized hip arthroscopy cannula system
1. Extra length cannulas
2. Shortened bridge accommodates extra length cannulas with standard
arthroscope
3. Cannulated obturators
- Allows prepositioning with spinal needle. Cannula/obturator assembly
can be passed over a guide wire initially placed through the needle
F. Extra length slotted cannulas allow passage of curved shaver blades
G. Extra length sturdy hand instruments
- Avoid instruments designed for other endoscopic purposes that might be less
sturdy and at greater risk of breakage
H. Radiofrequency devices exhibit distinct advantages in the hip
1. Maneuverability
2. Ability to effectively ablate tissue despite limits of maneuverability
II. Anesthesia
- Typically performed under general anesthetic. Epidural anesthesia is an appropriate
alternative but requires adequate block for assuring muscle relaxation.
1

ABC’s in the OR
J. W. Thomas Byrd, M.D.
III. Patient Positioning
A. Placed supine on the fracture table (Figure 1)
B. Heavily padded perineal post, lateralized against the medial thigh of the operative leg
(Figure 2)
1. Lateralizing the post adds a slight transverse component to the traction vector
(Figure 3)
2. Also lessens the likelihood of compression and possible neuropraxia of the
pudendal nerve
C. Operative hip positioned in extension, approximately 25 of abduction, and neutral
rotation
1. Slight flexion might relax the capsule and facilitate distraction, but can place
more traction on the sciatic nerve and draw it closer to the joint, making it
more vulnerable to injury. Thus, significant flexion is avoided during
arthroscopy.
2. Neutral rotation is important during portal placement (Figure 4) although
freedom of rotation during arthroscopy can facilitate visualization.
D. The contralateral extremity is abducted as necessary to accommodate positioning of
the image intensifier between the legs.
- Prior to applying traction to the operative leg, counter force is created by
placing the contralateral extremity under light traction. This stabilizes the
pelvis so that it does not shift as traction is gradually applied to the operative
extremity.
E. Traction is applied to the operative extremity and distraction of the joint confirmed
by fluoroscopy.
1. Typically about 50 pounds is applied. More force may be necessary for a tight
joint, but should be undertaken with caution.
2. Initially, adequate distraction (8-10 mm) may not be readily achieved.
a) Allowing a few minutes for the capsule to accommodate to the tensile
forces often results in relaxation of the capsule (physiologic creep) and
adequate distraction without excessive force.
b) Also, a vacuum phenomenon created by the capsular seal will later be
released when the spinal needle is introduced and the joint is distended
with fluid, which may further facilitate distraction.
F. After confirming the ability to distract the joint, the traction is released until ready to
begin the surgical procedure.
G. Peripheral compartment
1. Inspected after arthroscopy of intraarticular compartment
2. Traction released & hip flexed 45º
- Relaxes capsule & allows access to peripheral compartment
3. Especially useful for loose bodies, synovial disease, & thermal capsulorrhaphy

ABC’s in the OR
J. W. Thomas Byrd, M.D.
Figure1
Figure 3
Figure 4
Figure 2

ABC’s in the OR
J. W. Thomas Byrd, M.D.
IV. Portals
- The three standard portals are:
Anterior, Anterolateral, and
Posterolateral (Figures 5 & 6).
Figure 5
Table 1
Distance from Portal to Anatomic Structures
(Based on Anatomic Dissection of Portal Placements in Eight Fresh Cadaver Specimens)
Portals Anatomic Structure Average Range
Anterior Anterior Superior Iliac Spine
a Lateral Femoral Cutaneous Nerve
b Femoral Nerve (level of Sartorius)
(level of Rectus Femoris)
(level of Capsule)
Ascending branch of Lateral Circumflex
Femoral Artery
c Terminal Branch
(cm)
6.3
0.3
4.3
3.8
3.7
3.7
0.3
(cm)
6.0-7.0
0.2-1.0
3.8-5.0
2.7-5.0
2.9-5.0
1.0-6.0
0.2-0.4
Anterolateral Superior Gluteal Nerve 4.4 3.2-5.5
Posterolateral Sciatic Nerve 2.9 2.0-4.3
a
Nerve had divided into three or more branches and measurement was made to the closest
branch.
b
Measurement made at superficial surface of sartorius, rectus femoris, and capsule.
c
Small terminal branch of ascending branch of lateral circumflex femoral artery identified in
three specimens.
Figure 6

ABC’s in the OR
J. W. Thomas Byrd, M.D.
A. Anterior portal (Figure 7)
1. Positioning
a) Entry site is at the
intersection of a sagittal
line drawn distally
from the ASIS and a
transverse line across
the superior margin of
the greater trochanter
b) Directed approximately
45 cephalad and 30
towards the midline
c) Enters the joint under
the anterior margin of Figure 7
the acetabular labrum
(Position is facilitated by direct arthroscopic visualization)
2. Relationship to extraarticular anatomic structures
a) Penetrates the sartorius and rectus femoris before entering the anterior
capsule
b) At the level of this portal, the lateral femoral cutaneous nerve has
trifurcated
(1) One of these branches will usually lie close to the portal
(2) Most branches lie lateral to the portal
- Moving portal more laterally does not reliably avoid these
branches
- Moving portal medially is ill-advised because of closer
proximity to femoral nerve
(3) Laceration of the LFCN is avoided by utilizing careful technique,
not incising too deeply with the skin incision
(4) Although laceration can be avoided, neuropraxia of one of these
branches may occur due to manipulation of the cannula and
instrumentation from the anterior position (

ABC’s in the OR
J. W. Thomas Byrd, M.D.
B. Anterolateral (Anterior Paratrochanteric) Portal (Figure 8)
1. Positioning
a) Entry site is over the superior
margin of the greater trochanter at
its anterior border
b) Direction
(1) In the AP fluoroscopic view,
the portal passes immediately
above the greater trochanter
and then close to the superior
surface of the femoral head
to stay underneath the lateral
acetabular labrum.
(2) Accounting for normal
femoral neck anteversion,
with the hip in neutral rotation,
Figure 8
the portal courses parallel to the floor thus entering the hip joint
just anterior to its mid-coronal plane.
2. Relationship to the extraarticular structures
a) The anterolateral portal lies most centrally in the "Safe Zone" for
arthroscopy (Consequently it is the first portal established)
b) The portal penetrates the gluteus medius before entering the lateral
capsule
c) The superior gluteal nerve runs transversely an average of 4.4 cm cephalad to
the portal
C. Posterolateral (Posterior Paratrochanteric) Portal (Figure 9)
1. Positioning
a) Entry site is over the superior
margin of the greater trochanter
at its posterior border
b) Directed slightly cephalad and
anterior (converges toward
anterolateral portal)
c) Enters the joint underneath the
posterolateral margin of the labrum
(Entry location is performed under
direct arthroscopic visualization)
Figure 9

ABC’s in the OR
J. W. Thomas Byrd, M.D.
2. Relationship to the extraarticular structures
a) The portal pierces the gluteus medius and minimus before entering the
lateral aspect of the capsule posteriorly.
b) Like the anterolateral portal, the superior gluteal nerve averages a
distance of 4.4cm.
c) It enters the capsule superior and anterior to the piriformis tendon.
d) It lies closest to the sciatic nerve at the level of the capsule with an
average distance of 2.9 cm.
(1) Inadvertent external rotation of the hip during portal placement
will move the greater trochanter more posterior relative to the hip
joint. This will unnecessarily cause the posterolateral portal to
pass closer to the sciatic nerve. Consequently, external rotation is
avoided during initial portal placement.
(2) Hip flexion might partially relax the capsule and improve
distraction. However this will place more traction on the sciatic
nerve and may draw it closer to the joint, again placing it at more
risk for inadvertent damage. Thus, inordinate hip flexion during
hip arthroscopy should be avoided.
V. Portal Placement and Normal Arthroscopic Exam
A. Traction is applied to the hip
B. Anterolateral Portal
1. Placed first because it lies most centrally in the “safe zone” for arthroscopy
2. Prepositioning performed with a custom spinal needle (6", 17 gauge)
under fluoroscopic guidance
3. Joint is then distended with saline
4. Important to avoid penetrating the lateral labrum with the needle
a) The needle meets greater resistance penetrating the labrum and can be
felt during placement.
b) After distending the joint, if necessary, the needle can be repositioned
closer to the femoral head, further lessening the likelihood of piercing
the labrum.
5. A guide wire is passed through the needle and the
needle is withdrawn.
6. The cannula/obturator assembly is then passed over the
guide wire into the joint. (Figures10 & 11)
- As the assembly pierces the capsule, it is lifted up
to avoid grazing the articular surface of the
femoral head.
7. The 70 arthroscope is then introduced in the
anterolateral cannula.
Figure 10
a) Use of the 70 scope allows a direct view of where
the anterior and posterolateral portals enter the
joint simply by rotating the lens anteriorly and
posteriorly.
b) If there is a chance that the cannula may still have
pierced the labrum, at this point, excessive
maneuvering of the cannula should be minimized.
Figure 11

ABC’s in the OR
J. W. Thomas Byrd, M.D.
C. Anterior Portal
1. Prepositioned with spinal needle
a) Facilitated by fluoroscopy
b) Precise intracapsular positioning confirmed by direct arthroscopic view
2. As the cannula/obturator assembly enters the joint, again by utilizing
arthroscopic visualization, the labrum is avoided and the assembly is lifted off
the articular surface of the femoral head.
D. Posterolateral Portal
1. Rotating the arthroscope posteriorly in the anterolateral portal allows viewing
of the entry site for the posterolateral position.
2. Needle placement and introduction of the cannula are then carried out in the
standard fashion.
E. With all three portals established, the inflow is switched to the posterolateral portal.
1. A separate inflow optimizes flow dynamics.
2. With the inflow in the posterolateral cannula, bubbles tend to be flushed out
anteriorly, keeping them from obscuring the view.
F. The arthroscope is then switched to the anterior portal to critique positioning of the
anterolateral cannula.
- Once it is assured that the cannula is free of the labrum, it is then safer to
freely maneuver the instrumentation.
G. Systematic examination of the joint is then carried out from the three interchangeable
cannulas, using both the 70 and 30 arthroscopes.
1. The 70 scope is better for viewing the labrum, periphery of the acetabulum
and femoral head, and the deep recesses of the acetabular fossa and
ligamentum teres.
2. The 30 scope is better for viewing the central portions of the acetabulum and
femoral head and the superior portion of the acetabular fossa.
H. Instrumentation
1. Transverse capsular incisions improve maneuverability of the instruments
within the joint.
- These are created by passing an arthroscopic knife through the cannula
to incise the surrounding capsule.
2. Interchanging flexible cannulas allow passage of curved shaver blades for
maneuvering around the convex surface of the femoral head.
3. Extra length hand instruments can be passed through the cannulas.
4. With careful attention to the orientation, once the portal tracts have been
established, larger hand instruments can be maneuvered free-hand through
these tracts into the joint, such as for retrieving large loose bodies.

ABC’s in the OR
J. W. Thomas Byrd, M.D.
I. Peripheral compartment
1. Instruments removed, traction released, hip flexed 45º (Figure 12)
2. Arthroscope repositioned from anterolateral portal onto anterior neck of femur
(Figure 13)
- Prepositioned under fluoroscopy with spinal needle, guide wire &
cannulated obturator
3. Ancillary portal established 4-5 cm distally (Figure 14)
- Placed under arthroscopic visualization; prepositioning with needle
4. Peripheral compartment best inspected by:
a) Combination of 30 & 70º scopes
b) Switching between two peripheral portals
c) Rotation of hip
5. Often useful adjunct to arthroscopy of intraarticular compartment
a) Common area for loose bodies to reside, escaping detection when
viewing the intraarticular compartment
b) Allows access to synovium for generous synovectomy
c) Allows access to capsule for effective thermal capsulorrhaphy in cases of
instability due to incompetent capsule
Figure 12 Figure 13
Figure 14

ABC’s in the OR
J. W. Thomas Byrd, M.D.
VI. Arthroscopic Anatomy
A. Intraarticular compartment (Figure 15)
1. The following structures are reliably viewed:
a) Entire labrum
b) Entire lunate articular
surface of the acetabulum
c) The acetabular fossa
(including ligamentum
teres and pulvinar)
d) Most of the articular
surface of the femoral
head
e) Portions of the transverse
acetabular ligament
f) Capsule and capsular
reflection from the
labrum
2. Structures best viewed from the
anterolateral portal include:
a) Anterior acetabular
labrum
b) Anterior acetabular wall
c) Anterior surface of the
femoral head
Figure 15
3. Structures best visualized from
the posterolateral portal include:
a) Posterior acetabular labrum
b) Posterior acetabular wall
c) Posterior portion of the femoral head
4. Structures best visualized from the anterior portal include:
a) Lateral acetabular labrum and the relation of the lateral two portals
b) Anterior aspect of the transverse acetabular ligament
5. The acetabular fossa and its contents can be viewed with a different
perspective from each portal.
6. Approximately 75% of the weight bearing articular surface of the femoral head
can be viewed, facilitated by intra-operative rotation of the hip.

ABC’s in the OR
J. W. Thomas Byrd, M.D.
B. Peripheral compartment (Figures 16 & 17)
1. Visualization most reliably achieved for medial, anterior, and lateral portions
a) Peripheral labrum & capsular reflection
b) Peripheral aspect of femoral head
- Facilitated by ROM
c) Femoral neck
d) Medial synovial fold
- Consistent anatomic landmark
e) Zona orbicularis
- Circumferentially oriented coalescence of fibers creating capsular
collar around femoral neck
2. Posterior compartment least well visualized
a) Capsule tighter
b) Femoral capsular attachment more proximal
c) Closer proximity of sciatic nerve
Figure 16
REFERENCES
Byrd JWT: The Supine Position. In Byrd JWT (ed)
Operative Hip Arthroscopy Second Edition, New York,
Springer, 2005, 145-169.
Byrd JWT: Hip Arthroscopy, principles and application:
Smith & Nephew Endoscopy, 160 Dascomb Road, Andover,
MA 01810, 1996.
Byrd JWT: Operative Hip Arthroscopy (video). New
York, Thieme, 1998.
Byrd JWT, Pappas JN, Pedley MJ: Hip Arthroscopy: an
anatomic study of portal placement and relationship to the
extra-articular structures, Arthroscopy, 1995;11(4):418-423.
Byrd, JWT, Chern KY: Traction vs. distension for
distraction of the hip joint during arthroscopy, Arthroscopy,
1997;13(3):346-349.
Figure 17
Byrd JWT: Portal Anatomy. In Byrd JWT (ed) Operative
Hip Arthroscopy Second Edition, New York, Springer,
2005, 110-116.
Byrd JWT: Avoiding the labrum in hip arthroscopy,
Arthroscopy, 2000;16(7):770-773.
Dienst M, Gödde S, Seil R, Hammer D, Kohn D: Hip
arthroscopy without traction: in vivo anatomy of the
peripheral hip joint cavity. Arthroscopy 2001;17(9):924-
931.
Dienst M: Hip arthroscopy without traction. In Byrd JWT
(ed) Operative Hip Arthroscopy Second Edition, New York,
Springer, 2005, 170-188.

ABC’s in the OR
J. W. Thomas Byrd, M.D.
NOTES:

Safran
FAI – Dx & Rx
Page 1
Femoroacetabular Impingement (FAI):
What Is It, Making The Diagnosis, Imaging, Management and
Surgical Treatment
For 12 th Annual International Sports Medicine Fellows Conference
Carlsbad, California
January 29, 2012
MARC R. SAFRAN, MD
Professor, Orthopaedic Surgery
Associate Director, Sports Medicine
Stanford University
1) INTRODUCTION
a. Ganz and Associates Described FAI
i. First described in the Swiss Literature 1995
ii. First described in English Literature 1999
b. Conflict / abutment of the femoral head-neck region against the acetabulum
i. Generally antero-superior acetabulum
ii. Occurs with internal rotation
1. Less internal rotation needed to impinge with
a. Increasing flexion
b. Increasing adduction
2. May impinge in abduction
3. May impinge in flexion
4. Dependent on location of bony dysmorphology
c. Types
i. Cam
1. Loss of Offset at the femoral head neck junction
ii. Pincer
1. Overcoverage of the Femoral Head by the Acetabulum
iii. Combined
1. Most common that there are components of both
NOTES:

Safran
FAI – Dx & Rx
Page 2
2) CAM IMPINGEMENT
a. Loss of Femoral Head-neck offset
b. Result of aspherical head-neck region
i. Femoral head epiphysis protrudes laterally out of a circle outlining femoral head
ii. Pistol Grip deformity
iii. Lateral contour of the femoral head extends in a convex shape to the base of the
femoral neck
iv. Pathophysiology
1. Cam lesion goes under the labrum resulting initially in a labral-chondral
separation.
a. Later intra-substance labral tearing
2. Articular cartilage delamination of acetabulum
3. Predominantly anterosuperior damage
a. Deep and more focal
3) PINCER
a. Relative overcoverage of the femoral head by the acetabulum
b. Several types / causes
i. Coxa Profunda (deep hip)
1. Floor of the Acetabular fossa touches the ilioischial line and center edge
angle >35 degrees
ii. Protrusio (otto pelvis, coxa protrusio)
1. Femoral head crosses the ilioischial line
iii. Retroversion
1. Posterior wall of acetabulum is medial to center of the femoral head
iv. Cranial Retroversion
1. Upper portion of the anterior acetabulum crosses the posterior border
medial to the lateral edge of the acetabulum
2. Figure of 8 or crossing sign.
v. Ossified Labrum
1. Deepens acetabulum functionally
c. Pathophysiology
i. Labrum crushed between the Acetabular rim and femoral head-neck region
1. Crush labrum
2. notching femoral head – neck region
3. Chondral damage shallow but more global
a. Not just antero-superior
4. ContreCoup injury
a. Femoral head-neck levers on Acetabular rim
b. Posterior femoral head Chondral damage
c. Posterior labral and acetabular injury
NOTES:

4) COMPENSATORY ISSUES
a. Concept – some evidence suggesting (Birmingham, et al)
b. Hip with limited range of motion at femoroacetabular joint
c. As try to maintain stride length or hip motion with athletic activities, compensate for
limited femoroacetabular motion
i. Increase stress on other local joints
1. Pubic symphysis
a. Result in osteitis pubis
b. Sports Hernia as try to stabilize pubic symphysis
2. Sacro-Iliac Joint
a. SI Joint Dysfunction
3. Lumbar Spine
a. Facet joint inflammation
b. Disc degeneration / herniation
5) PRESENTATION
a. History
i. Uncommon to have a history of trauma
1. Usually insidious onset
2. Traumatic injury may be the straw that broke the camel’s back
ii. Groin Pain
iii. Aching
iv. Difficulty putting on socks and/or shoes
v. Worse with activity
vi. Worse with prolonged sitting
vii. Pain with
1. Squatting
2. Cutting / Pivoting
3. Sudden Stop / Starts
4. Going up stairs
viii. May report limited range of motion
1. Flexion
2. Internal rotation
3. Adduction
ix. Often reported as a recalcitrant hip flexor strain
x. May have mechanical symptoms
1. Locking
2. Catching
3. Sharp pain
xi. Not uncommon to have had other previous surgeries without success
NOTES:
Safran
FAI – Dx & Rx
Page 3

NOTES:
b. Physical Examination
i. See Hal Martin’s Work for complete Evaluation
ii. My exam
1. Observe Sitting
2. Trendelenberg
3. Gait
4. Hip Flexion
5. Hip Rotation (in 90 degrees flexion)
a. Internal
b. External
6. Impingement Test
a. Internal rotation of hip that is flexed to 90 degrees and adducted
7. Labral Stress (Scour) Test
a. Start in Flexion, Abduction and external rotation
i. Move into adduction, extension and internal rotation
b. Then Start in Flexion, Adduction and internal rotation
i. Move into abduction, extension and external rotation
8. FABER for motion
9. Other Commonly Performed Tests
a. Supine
i. Hesselbach’s Test
ii. Resisted Sit Up
iii. Resisted Straight Leg Raise
iv. Patrick’s Test
v. Log Roll
1. Pain
2. Amount of Rotation
vi. Thomas Test
vii. Hyperextension – External Rotation
1. Posterior Impingement
2. Anterior Instability
viii. McCarthy’s Test
ix. Byrd’s Test for Snapping Hip
1. Variations
x. Posterior Apprehension
xi. Lasegue’s
xii. SI Joint Stress with Leg over table
b. Lateral
i. Tenderness of the Trochanter
ii. Tenderness of the Gluteus Medius
iii. Tenderness of the Piriformis
iv. Ober Test
v. Bicycle Test for Snapping
vi. Pelvic compression
Safran
FAI – Dx & Rx
Page 4

6) IMAGING
a. Plain XR
i. AP Pelvis
1. Coccyx Centered 1-3 cm above Pubic Symphysis
2. Symmetric Obturator Fossae
ii. Lateral of the hip
1. Cross Table
2. Dunn View or Modifications
iii. Pitfalls
1. Frog Lateral good lateral for proximal femur but not acetabulum
2. AP of the Hip is not the Same as an AP of the Pelvis
iv. Additional views
1. AP of the Hip
2. False Profile View
v. Proximal Femur
1. Sphericity
2. Symmetry
3. Version
4. Neck Shaft Angle
5. Notching
vi. Look at Acetabulum
1. Depth
a. Relative to Ilioischial Line
i. Floor of Cotyloid Fossa (profunda)
ii. Femoral head (protrusio)
b. Center-edge angle
2. Acetabular Index
3. Crossing Sign
4. Peri-articular Ossifications
a. Labral Ossification
b. Os Acetabuli
c. Rim Stress Fracture
b. MRI
i. Small field of view ((FOV) MRI better
1. MRI of the hip better than MRI of the Pelvis
ii. Arthrography more sensitive
iii. 3T better than 1.5 T
iv. I prefer adding Anesthetic (Ropivicaine) to see if pain reduced
1. Assure pain coming from inside the joint
c. 3D CT Scan
i. Better assessment of bony morphology
ii. Some get all the time
iii. Risk of fair amount of radiation
NOTES:
Safran
FAI – Dx & Rx
Page 5

d. Alpha Angle
i. Defined on Radial Cut MRI Imaging
1. People use with XR, CT, and non Radial MRI
ii. Angle Made by drawing a line from the Center of the femoral head
1. To the center of a line at the narrowest part of the femoral neck
2. To the point where the femoral head exceeds the a sphere set to the
circumference of the femoral head
iii. Normal less than 50 – 55 degrees
iv. Insurance companies want to see this number
v. Poor inter and intra-observer reliability
vi. Does not correlate with clinical success of the surgery
7) TREATMENT
a. Non operative
i. No proven benefit
ii. Treat compensatory changes / loss of strength
1. Core strengthening
2. Often hip abductor weakness
iii. Do not force ROM
1. Increases impingement
iv. Avoid Deep Squats
v. Recreational athletes – shorten stride length with running / jogging
b. Operative
i. ROM without abutment
1. Eliminate impingement
2. Restore Femoral Head-Neck offset
a. Chielectomy / Femoral Osteoplasty
3. Address Acetabular overcoverage
a. Acetabuloplasty / Acetabular osteoplasty
ii. Address associated pathology
1. Labral
a. Repair
b. Resect
c. Reconstruct ?
2. Chondral
a. Debride
b. Microfracture
c. Repair ?
NOTES:
Safran
FAI – Dx & Rx
Page 6

Safran
FAI – Dx & Rx
Page 7
8) RESULTS
a. Problems with results
i. Most are short term
ii. Published studies to date lack good quality of life score for non-arthritic hips in
younger active patients
1. IHOT
b. Comparative Systematic reviews
i. Matsuda, et al, Arthroscopy, 2011
ii. Botser, et al, Arthroscopy, 2011
c. Systematic Reviews
i. Ng, et al, Am J Sports Med 2010
ii. Clohisy, et al, Clin Orthop, 2010
iii. Bedi, et al, Arthroscopy 2008
d. Results similar
e. Morbidity and Complications less with Arthroscopy
9) CONCLUSION
a. FAI is an important cause of hip pain
i. Associated with Labral Damage
ii. Associated with Chondral Damage
iii. Associated with Early Arthritis
b. 2 Main Types
i. Cam
ii. Pincer
iii. Most people have combination of both to varying degrees
c. Treatment is Usually Surgical
d. Open, Arthroscopic and Combined techniques are safe and effective
i. Long Term Follow Needed
ii. Follow Up using validated outcomes measures for active patients without arthritis
critical
e. Must treat impingement as well as associated labral and Chondral pathology

Definition:
Sports Hernia – Diagnosis, Algorithm and Surgical Treatment
William Hutchinson, MD USA
Sports hernias include basically the area of the umbilicus to the mid thigh and
are without a bulge in the inguinal area. There are many definitions and
names for these so-called sports hernias and none seems to incorporate the
exact problem. These hernias include skin, fat, fascia, muscle, vessels,
tendons, cartilage, bone, and nerves. The nerves seem to be the most
important as they transmit the pain or discomfort from the site of pathology.
Occasionally they are the only thing involved in the so-called sports hernia.
Diagnosis:
There are a myriad of presentations with the various injury involved and to try
to use a simple set of questions is almost impossible with these hernias. An
attempt will be made to outline a set of questions that will help separate the
various types of sports hernias.
Sports Hernias Examples:
Pictures and cases reports will be included to show of the more common
presentations.
Treatment:
An attempt will be made to try to outline some of the various treatments for the
more common sports hernias. These will all be related to those treated by the
general surgeon as opposed to the orthopedic injuries which will be covered
by other presentors.

Michael B. Gerhardt, MD
Player details
� 28 year old male professional soccer
player
� Midfielder for Major League Soccer
franchise in the United States
� Drafted in 2002 after four year college
career in the United States
History of present complaint
� Right hip pain developed in opening
months of MLS season 2009
� Able to complete competition with
conservative measures
� NSAIDs
� Stretching
� Ice
� Modified practice schedule
� Progressed from soccer related pain to
daily pain in most activities
Chief Complaint
Michael B. Gerhardt, MD
Team Physician
LA Galaxy, CD Chivas USA
US Soccer
� Right hip and groin pain
Past surgical history
� Right sports hernia repair 1 year prior*
*2008 Muschaweck repair, Munich,
Germany – successful return to play
4 weeks after surgery
1/23/2012
1

Presenting physical examination
� Pain with impingement maneuver of
right hip
� Flexion, internal rotation
�� Ten degrees internal rotation right side
vs twenty degrees on the left
Ext Flex IR ER Abd
Right -10 10 125 10 60 65
Left -10 10 125 20 60 65
Physical examination
� Positive sports hernia exam
○ Rocker’s test
○ Resisted hip adduction
○ Hesselbach’s test
AP Pelvis Lateral Right Hip
CAM Lesion
1/23/2012
2

CAM Lesion Labral Tear
Summary
� 28 year old male professional soccer
with new onset HIP PAIN and
RECURRENT GROIN PAIN
� Hip pain secondary to CAM impingement
and labral tear
� Groin pain secondary to recurrent sports
hernia
� Failed prolonged conservative treatment
� Desires return to professional soccer
Labral tear Synovitis
Management – Phase I
� Right hip arthroscopy (November 2009)
� Findings
� Primarily CAM impingement
�� Anterolateral labral fraying
� Grade II articular cartilage defect at
anterolateral acetabulum
� Partial tear of ligamentum teres
� Synovitis
1/23/2012
3

Ligamentum teres partial tear CAM Lesion
What was done
� Labral debridement
� Femoroplasty
� Chondroplasty
� SSynovectomy t
� Ligamentum teres debridement
Cam lesion – requiring
femoroplasty
Labral tear and chondral
delamination – consistent
with cam FAI
Postoperative AP Pelvis
1/23/2012
4

Postoperative Lateral
Management – Phase II
� Right groin sports hernia repair
(December 2009 - 3 weeks following
hip arthroscopy)
�� Findings
� Posterior inguinal deficiency (transversalis
fascia)
� Ilioinguinal nerve entrapment
Rehabilitation
� No crutches – weight bearing as
tolerated
� Gentle progressive stretching program
�� Stationary bike starting POD #7
� Hip arthroscopy protocol continues
Rehabilitation
� Partial weight bearing 14 days on
crutches
� Continuous passive motion for two
weeks
� Rehabilitation inititated at 14 days
What was done
� Sports hernia repair
� Posterior ing wall imbrication (no mesh)
� Ilioinguinal neurolysis
Current Status
� Rehabilitated with MLS team staff
� Trainer
� Strength and Conditioning coach
�� Returned to full competition March 2010
MLS season opener (5 months)
1/23/2012
5

Relationship of Hip Injuries and
Sports Hernia
� Dual diagnosis
� Likely relationship between hip
morphology and development of hip and
groin injuries
� VERY COMMON PROBLEM IN
SOCCER PLAYERS THROUGHOUT
THE WORLD!!!
� Area of ongoing research – FIFA funded
Sports Hernia
Current research
-Professional soccer
players
-Incidence of xray
abnormalities – FAI
-Correlation with
previous sports hernia
**Prospective look at development
of FAI symptoms and/or sports
hernia
Scope of the Problem
� Harris, Dietz, Gerhardt, and
Mandelbaum
� Identifies relationship between
RADIOGRAPHIC abnormalities of the hip
and prevalence of HIP AND GROIN
INJURIES in the professional soccer athlete
Sports Hernia
Common duality
Sports Hernia +
Hip Disorder
� Theory
1. Pre-existing FAI
2. Limited Hip ROM
3. Compensatory stress groin/pelvis
4. Development of Sports Hernia
Scope of the Problem
� Harris, Dietz, Gerhardt, and
Mandelbaum
� “The Prevalence of Radiographic
Abnormalities in Elite Soccer Players” y
� Radiographs of 95 elite level soccer players
� Abnormal radiographs
○ 72% men
○ 50% female
Labral Tears in young population
� Ganz et al. CORR 2003
� Femoroacetabular impingement as the primary
cause of labral tears in the nondysplastic hip
� CAM effect
○ Anterosuperior acetabular cartilage and labral shearing
○ Anterosuperior acetabular cartilage and labral shearing
� Pincer effect
○ Labrum caught between acetabulum and femoral neck
○ Peripheral and circumferential labral degeneration
1/23/2012
6

Bedi et al. The Management of Labral Tears and FAI of the hip in the
Young, Active Patient. Arthroscopy 2008 Return to play after hip
arthroscopy
� Phillipon et al AJSM 2009
� 28 professional hockey players
� Acetabular rim trimming, femoral neck
osteoplasty, p y and labral repair p
� Average age 27 years old
� Return to skating/drills at 3.8 months
� Average of 94 games played at 2 years
postop
Is it the labrum or FAI?
� Philippon et al. AJSM 2007
� 37 patients for revision hip arthroscopy
� Persistent pain 21 mos after index
procedure p
� 36/37 had evidence of FAI on xray that was
not/inadequately addressed
� Underlying FAI pathology treatment is critical
in treating labral pathology
Sports Hernia
History
Current research
US Men’s National
Soccer Team
-37.5% sports
hernia surgery
-12.5% bilateral
-66% dual diagnosis
>>sports hernia + FAI morphology
Return to play after hip
arthroscopy
� Bharam Clin Sports Med 2006
� Average return to play for labral surgery
� No impingement surgery performed
� Golf: 6 weeks
� Hockey: 10 weeks
� Baseball and soccer: 12 weeks
Sports Hernia + FAI
Conclusion
*FAI and Sports
Hernia common
in in elite elite athletes athletes
*Addressing BOTH
diagnoses may be
indicated
*May result in lower
recurrence rates
1/23/2012
7

Thank You
1/23/2012
8