Platelet Rich Plasma (PRP)

• Arthroscopic Treatment of Cartilage Lesions
Using a PGA Scaffold with Hyaluronic Acid
Dr Alberto Siclari
S.C. di Ortopedia e Traumatologia
Direttore dr E. Boux
Ospedale degli Infermi di Biella
ASL BI - Piemonte

• The management of cartilage loss continues to
be a challenge to trauma and orthopedic
surgeons
• The introduction of pluripotent mesenchymal
stem cells into the clinical settings opens new
horizons

• Can we maximize the mesenchymal cells
potential to produce cartilage ?
• Can we use a simple procedure ,
with low impact for the patient ,
to restore damaged cartilage ?
• Can we report these results
to have a good follow up?

• Yes , we can ! .....
• ( Thank you Mr President.......)
• But , we need also .....
1) a scaffold
2) a grownth factor
3) A lot of mesenchimal stem cells
to produce a hyaline-like cartilage .
So we can say that .........

Cartilage is just like a skyscraper
Then we add
growth factors
that attract ......
......... the
Mesenchymal
cells and stimule
to differentiate
them ....
... in
chodroblasts
to produce
cartilage
At first we put a
scaffold

1) The scaffold
• Polyglycolic acid + hyaluronic acid scaffold
chondrotissue ®
( BioTissue )

• Macromolecolar
polymer
• High hidrophily
• High viscoelasticity
High stress resistence
• Totally reabsorbable

2) Growth factor
• Platelet Rich Plasma (PRP): divided from the
other blood fractions by centrifugation

Platelets if activated release the alfagranules
in the extracellular matrix.
We can find three kinds of GF that have
proliferative and differentiative effects :
1) TKR GF ( TyrosineKinase Receptor ) (PDGF)
2) SMAD GF ( SerineThreonine KinaseR.) (BMP
+TGF Beta)
3) FGF ( Mitogen-activated Receptor?)

FGF ( Mitogen-activated Receptor?)
• FGF = Fibroblast GF
• Probably it works like a regulator
• It’s an antagonist of BMP and induce MSCs to
develop into fibroblasts and not in
chondroblasts
• Minina E , et al. “Interection of FGF and BMPsignaling integrates chondrocytes proliferation “ Dev Cel
2002;3:439-448

How do they work ?
Grownth Factors
• Receptors in cell membrane
• Activation of a transcription factor ( Sox9 mainly)
• Nucleus
• Activation of a gene ( or genes ?)
• Proliferation or differentiation

3)Mesenchymal stem cell MSC

• Mesenchimal stem cells are non-haemopoietic
stromal cells that exhibit a multilineage
differentiation capacity.
• MSC can develop into chondrocytes, osteoblasts,
myocites, neural cells and adipocytes
• It’s possible to guide MSC into a specific type using
specific grownth factors or other subtances
( chondrogenesis : toluidine blue stain )
• MF Pittinger et al.Multilineage potential of adult human MSCs Science 1999;
284 :143-7

• Mobilisation and differentiation of MSC are
influenced by chemotaxis and by interaction
with the extracellular matrix .
• However , MCS are influenced by
microenviroment
• WR Otto Tomorrow’s skeleton staff MSC and the repair of bone and cartilage
Cell Prolif 2004 ; 37: 97-110

• Mesenchymal stem cells can be recovered in
articulation and in a collagenic scaffold after
microfractures.
• J. Kramer et al. “In vivo matrix-guided human mesenchymal stem cells”
Cellular and molecular life sciences 2006,vol 63 n°5 pp. 616-626

Clinical Application
• 1) cartilage lesions of the knee
• 2) cartilage lesions of the talus
• 3) hallux rigidus

The idea
Cartilage Lesion
Curettage
Microfracture for MSCs to come in scaffold
Positioning of the scaffold
Grownth factor
Cartilage

Clinical Application: the KNEE
From July 2007 to September 2009 we treated:
• 97 patients with chondral lesions of the knee
for a total of 111 surgeries

• MRI
• Lesions
grade 3-4
Diagnosis

• Chondral lesions of the knee : 65% tibial and
35% femoral
• 21 patients had a kissing lesion
• The largest lesion was 5 cm2 • The average age was 44.8
• 68% women 32 % men

The procedure
• The surgery is completely done by arthroscopy
and consists of three parts:

• In the 1 st part the subchondral bone is exposed by removing
the damaged cartilage and microfractures are performed.

• In the 2 nd part the scaffold
( chondrotissue ® ,
BioTissue) is soaked with
PRP and is implanted in
the lesion .
• If the lesion is femoral the
scaffold is fixed with a
resorbable pin .

• In the last part of the
procedure the scaffold
is covered and soaked
with a gel obtained from
the PRP

• The patient is discharged after few hours.
• After 15 days the patient may walk with
crutches and a partial load for one week and
then with normal load.

Results
• 52 patients have been evaluated with the
KOOS score :
pre-OP and then after 3, 6, and 9 months

Rule out
• The exclusion criteria were: present infections,
important articular instability, haemophilia,
allergy to the scaffold constituents,
alterations of the femoro-tibial angle > 2°,
nocturnal pain caused by overload
• Age limits: 25-65 years

• The average pre-OP score was 38.55 pts :
during the first control the value rose to
62.45 , during the second one to 63.58 ,
during the third one to 65.87 , and during the
fourth one to 69.97 ( p-value

Symptoms
Pre-OP : 56.3 +- 10
First control : 75.2 +- 9
Second control : 78.7 +- 7
Third control : 86.4 +- 8
Pain
Pre-OP : 54.1 +- 15
First control : 78.2 +- 8
Second control : 83.3 +- 8
Third control : 89.6 +- 9
Daily activities
Pre-OP : 68.1 +- 18
First control : 78.5 +- 17
Second control : 82.7 +- 14
Third control : 85.3 +- 15 Sport
Pre-OP : 35.5 +- 14
First control : 57.7 +- 19
Quality of life
Pre-OP : 37.2 +- 13
First control : 59.7 +- 14
Second control : 65.4 +- 10
Third control : 70.5 +- 9
Second control : 62.4 +- 12
Third control : 68.8 +- 13

• Average KOOS
• Pre-OP : 50.78
• First control : 70.06
• Second control : 74.70
• Third control : 80.12

• 7 patients had a kissing lesion
• Average age 44.3 yr ( 31-65 yr)
• Average follow up 13.07 m ( 9-17 months)

• 10 patients have been re-evaluated with a
second arthroscopic look 9 months after the
first implant with a biopsy and a histological
examination.

• The arthroscopic appearance during the
second look was a cartilaginous tissue, whiter
than the other cartilage, smooth but with
some little corrugation, with a consistence
similar to normal cartilage, stuck to the bone

• The histological examination reported in all
10 cases the complete disappearance of the
scaffold and the presence of a new
cartilaginous tissue similar to hyaline
cartilage.

• Struttura Complessa di Medicina Rigenerativa
• Director Prof. Ranieri Cancedda
• Department of Biology, Oncology and Genetics,
University of Genoa

Complications
• In 7 cases an articular effusion was drained
with a needle during ambulatory controls. No
infections or TVP were reported.
• The range of motion was reduced of 20-30°
in the first month, and gradually rose to the
pre-OP level in the first three months.

Discussion
• Clinical results are favourable : only after the
first control the score increases by 19.28
points. 90
80
•
70
60
50
40
30
20
10
0

• The possible explanation is found assessing
the features of the scaffold used : its structure
is very hydrophilic and inside the articular
cavity it works like a “pillow” in the lesion
giving soon a smooth and elastic surface .

Clinical Appliacation: the ANKLE
• 8 patients with chondral lesions of the talus
• All lesions were superomedial
• 6 patients with positive anamnesis for ankle
distorsion

Notes on the preliminary results
• Short follow-up : 3-15 months
• Loading recovery after 15 days
• Fast pain relief
• No complications, moderate post-OP pain
• Unaltered range of motion
• No arthroscopic second look

Clinical Application: the FOOT
• Hallux Rigidus
• Grade 0 ( FD 40-60° )
• I ( FD 30-40° )
• II ( FD di 10-30° )
• III ( FD < 10° )
• IV ( sub-ankylosis)
• Coughlin –Shurnas 1999

• Cheilectomy
• Osteotomy F1
• Arthroscopy
• Metatarsal ostetomy
Suggested treatments
• Arthroplasty with biological implant
• silicone implant
• metal implant
• Arthrodesis

Indications
• Grado 0 arthroscopy
• I arthroscopy
• II arthroplasty with scaffold
• III arthroplasty with scaffold
• IV artoplasty with scaffold/arthrodesis

Results
• 17 patients for a total of 19 feet
• 7 of grade II
• 8 of grade III
• 4 of grade IV
• Follow-up 12-21 months

• AOFAS Score
• average pre-OP value 61,3
• average post-OP value 91
• average pre-OP ROM value 24,5
• average post-OP ROM value 56,3

As Leonardo would
write.... uoY knaht ro
...........................
Thank you!