30845 Suppl Giot.pdf - Giornale Italiano di Ortopedia e Traumatologia

G.I.O.T. 2010;36(suppl. 1):S140
Chitosan for cartilage defects
Chitosano nei difetti cartilaginei
F. Forriol
Chitosan is a linear polysaccharide composed of randomly
distributed D-glucosamine (deacetylated units) and N-acetyl-Dglucosamine
(acetylated units), soluble within an acid environment.
When its deacetylation degree is less than 60%, it is then
called Chitin. The latter is the second most abundant natural
polymer on earth after cellulose. Chitosan has a great variety of
applications in several fields, the biomedical one being of the latest
and more promising among them. It can be worked out so as to
have the product available in various forms such as nanoparticles,
microspheres, hydrogels, films, fibers or enteric coats.
Its cationic nature gives Chitosan an interesting property, namely the
ability to adhere to negatively charged surfaces such as living tissues
and mucosal membranes, allowing also the transport of polar substances
such as drugs across epithelial surfaces 1 . When it breaks down,
the byproduct is composed from chains of glucosamine, a natural component
of tissues such as articular cartilage. Its toxicity is almost null,
making it a highly biocompatible and biodegradable substance.
Wound healing is one of the most popular uses for Chitosan in
the biomedical field. Some of the reasons which make Chitosan
based products so suitable for this use are its haemostatic capabilities
2 , its anti-inflammatory effects 3 4 , a proven antimicrobial
action 4 , and the ability to retain or attract some growth factors
which are part of the healing processes 5 .
More advanced uses of Chitosan such as for articular cartilage
repair or gene therapy processes 6-8 are being studied presently
with very encouraging results so far. Applications such as bone
regeneration, alone or in combination with more substances (like
calcium phosphate) are also being tested presently 1 .
One of the drawbacks of Chitosan has to deal with the fact that it
is soluble only within acid environments that are beyond physiological
levels. Some constructs have being used to overcome
this problem, making its use possible at a liquid state, and thus
enhancing its parenteral and local delivery capabilities. It can be
used also as a thermogel, with the ability to be delivered in liquid
form and then using the body temperature to transform itself into
a gel with different residency time frames as well as different
mechanical properties 9 . They are applied as space-filling agents,
delivery vehicles for bioactive molecules and as three dimensional
structures. They act as biodegradable scaffolds that can support
the repair or regeneration of a new tissue. This application is
being tested presently in clinical trials for cartilage repair.
As more research is being conducted, more surprising roles for a
polysaccharide like Chitosan are being discovered, especially in
the biomedical field. It use is expected to keep on growing in the
coming years.
Madrid, Spain
S140
In clinical practice, microfractures, MSC and blood from the spongy
metaphyseal bone are lost in the joint, and the injury is repaired with
fibrocartilage, a tissue that is ill suited to bearing mechanical loads.
To prevent this, an effective low-cost solution is to cover the area of
the injury that has been perforated with an adhesive polymer, could
be chitosan, so that the bleeding, with its cells and growth factors,
is soaked up by the polymer to achieve what has been described as
ICI (in situ chondro-induction), using the chitosan as a scaffold that
prevents the blood clot from retracting, thus filling the defect and
staying in place; as this scaffold is cationic, it establishes a strong
adherence to the walls and floor of the lesion, which are anionic. It
also protects the blood platelets, keeping their normal functionality
(releasing the various growth factors needed to trigger the inflammatory
response, among them the PDGF), and maintaining their levels
for a longer period of time. With this and other effects, the basis for
what is called SGRM (Scaffold Guided Regenerative Medicine), is
set, complemented with the already mentioned ICI 7 .
There a lot yet to be done, but repair of the avascular tissues poses many
difficulties, and it will be necessary to explore these potential options
carefully and proceed by means of elimination, in order to reach the
solution that all of us desire. One that will be cost - effectivity, produces
the right target tissue and is surgically attainable by the average
surgeon. That would be the true innovation that the orthopaedic community
is looking for to solve the problem of secondary osteoarthritis
and its increasing burden on the health systems around the world.
rEFErENCES
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2 Pusateri AE, McCarthy SJ, Gregory KW, et al. Effect of a chitosan-based
hemostatic dressing on blood loss and survival in a model of severe venous
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