Évaluation des réponses cellulaires et tissulaires précoces induites par des implants sous-chondraux et présolidifiés composés de chitosane/sang dans un modèle ostéochondral
Year: 2011
Type: dissertation
Abstract: RESUME
Les lesions du cartilage articulaire sont tres repandues et engendrent des douleurs intenses ainsi que des pertes de fonction au niveau des articulations. Les lesions du cartilage articulaire s’averent en plus etre une des pathologies du corps humain qui sont les plus difficiles a traiter. Le cartilage est un tissu avasculaire contenant peu de cellules, ce qui lui confere des proprietes de regenerescence intrinseque tres faibles. Son architecture complexe de collagene et de proteoglycanes lui confere des proprietes de resistance aux compressions et d’elasticite avantageuses, mais les tissus de reparation typiquement formes suite a la reparation d’une lesion ne repliquent souvent pas la composition exacte du cartilage articulaire, ni l’organisation de sa matrice extracellulaire. Les tissus de reparation autologues sont donc mecaniquement inferieurs aux tissus sains, ce qui se traduit par une perte de stabilite de l’articulation qui peut mener a des douleurs, a des pertes de mobilite et meme a la degenerescence chronique du joint synovial. En effet, les lesions qui ne sont pas traitees adequatement degenerent souvent en arthrose. Le developpement de nouvelles therapies pour la regenerescence du cartilage est donc une priorite.
Afin de traiter des lesions focales du cartilage articulaire, plusieurs traitements sont disponibles. Par exemple, l’implantation de chondrocytes autologues a un taux de succes eleve, mais constitue un traitement couteux qui requiert un minimum de deux chirurgies. De plus, une etude clinique n’a demontre aucun avantage clinique par rapport aux techniques de stimulation de la moelle osseuse. Ces techniques consistent en la perforation de trous au sein de la lesion prealablement debridee jusqu’a l’os sous-chondral afin de causer le saignement de l’articulation et ainsi permettre aux cellules souches de la moelle osseuse d’acceder au cartilage. Malgre les avantages de cette technique, le tissu de reparation est souvent un tissu de type fibrocartilagineux, ce qui le rend moins resistant aux charges mecaniques. Il a aussi ete demontre que les patients âges repondaient beaucoup moins bien a ces techniques.
Afin de pallier les reponses de reparation cartilagineuse de ces traitements qui sont inadequates, notre laboratoire a developpe un implant hybride de chitosane, un polymere naturel biodegradable et biocompatible, de glycerol phosphate (GP) et de sang autologue. La solidification de l’implant est ainsi causee par la coagulation du sang contenu dans l’implant. Cet implant permet de stabiliser le caillot sanguin sur des trous chirurgicaux perfores par microfracture ou par percage. Plusieurs etudes pre-cliniques ont ete faites et concluent que les----------ABSTRACT
Articular cartilage lesions are very frequent and lead to intense pain and loss of articular function. Lesions of the articular cartilage are also one of the hardest pathologies to treat in human. Cartilage is an avascular tissue that contains few cells, which results in poor intrinsic regeneration properties. Its complex architecture composed of collagen and proteoglycans results in advantageous properties of resistance to compression and elasticity, but the repair tissues that are formed following typical cartilage repair treatments of a lesion do not replicate the exact composition of articular cartilage and the organization of its extracellular matrix. Autologous repair tissues are thus mechanically inferior to healthy tissues, which translates to a loss of stability of the articulation that can lead to pain, loss of mobility and even chronic degeneration of the synovial joint. Lesions that are not properly treated often degenerate in osteoarthritis. The development of new therapies for cartilage repair is thus a priority.
To treat focal lesions of the articular cartilage, various alternatives are available. For example, the implantation of autologous chondrocytes has a high rate of success, but consists of a costly treatment that requires a minimum of two surgeries. Additionally, a five years clinical study has shown that it had no apparent clinical benefit compared to bone marrow stimulation techniques. These procedures consist in creating surgical holes in the debrided lesion to perforate the subchondral bone and induce bleeding in the articulation to allow marrow-derived stem cells to access the cartilage. Despite the advantages of this technique, the repair tissue is often made of fibrocartilage, which makes it less resistant to load-bearing. It had also been shown that aged patients did not respond as well as young patients to these techniques.
As a solution to the inadequate cartilage repair response to current treatment modalities, our laboratory has developed a hybrid implant of chitosan, a natural polymer that is biodegradable and biocompatible, glycerol phosphate (GP) and autologous blood. The solidification of this implant is caused by the coagulation of the blood. This implant allows the stabilization of the blood clot over microfracture or microdrilling defects. Many preclinical studies have been performed and have concluded that chitosan-GP/blood implants lead to the synthesis of a repair tissue that is more hyaline and integrated to the resident tissue after 8 weeks in a skeletally mature rabbit model. The short term events associated with this satisfying cartilage repair are a strong recruitment of neutrophils and osteoclasts, a delayed synthesis of the principal elements of
Language: French
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Awards: G4950347942, G6127854273
OpenAlex ID: W149068059