Cartilage defect regeneration by ex-vivo engineered autologous mikro-tissue

Objectives: Advances in the understanding of ex-vivo tissue formation are recently applied to improve tissue engineering strategies in order to regenerate destructed tissue. Temporomandibular joint deformities, present in cases of arthrotic TMJ disorders, are clinical examples of lost cartilage tissue. Biological regeneration therapies have special promise in functional restitution strategies. Methods: In this pilot experimental study we tested whether autologous chondrocyte-like cells, building up a mikro-tissue in culture, can improve cartilage defect regeneration after transplantation in superficial cartilage defects. For this purpose, cartilage defects were surgically introduced into joints of five minipigs. Autologous chondrocytes previously harvested from minipigs were multiplicated in culture and assembled without a scaffold to a mikro-tissue. The defects were then treated by implanting the tissue constructs. Defects without cell transplantation served as a control. Results: The ex-vivo culture of chondrocytes led to the formation of a mikro-tissue containing chondrocyte-like cells in a self assembled cartilage-like extracellular matrix. The clinical inspection after a healing period of 60 days demonstrated a nearly complete cartilage regeneration in the cell treated defect sites. The implanted chondrospheres appeared to be able to form hyaline cartilage as confirmed by histological and immunohistochemical analyses. Conclusion: These results indicate that in vitro expanded chondrocyte-like cells are able to build up a mikro-tissue capable of repairing superficial cartilage defects in vivo. These results warrant further attempts to elaborate cell/matrix transplantation without the use of artificial scaffolds to restore impaired joint structure and function.