Biofabrication of implants for articular joint repair : Cartilage regeneration in reinforced gelatin-based hydrogels

Abstract

Implants were biofabricated for the repair of chondral and osteochondral articular joint defects. The implants were based on gelatin methacrylamide (GelMA) hydrogels combined with printed fibers from polycaprolactone (PCL) for mechanical reinforcement. In Part I of the thesis, biological modifications of GelMA by the addition of matrix derived from cartilage, meniscus or tendon tissue did not show a positive effect on in vitro cartilage matrix production by encapsulated chondrocytes or MSCs. Furthermore, MSCs in GelMA in a subcutaneous rat model could not be locked in their chondrogenic state, considering the evident process of endochondral bone formation in these constructs. Both the quantity and quality of bone formed by MSCs in GelMA are nonetheless encouraging for bone tissue engineers. In Part II, hydrogels were successfully reinforced with PCL microfibers. These hydrogel/microfiber composites approached the stiffness and elasticity of articular cartilage and permitted the formation of cartilage matrix by embedded chondrocytes. The repair of focal cartilage defects with reinforced GelMA gels is currently evaluated in eight Shetland ponies, with a follow-up of one year, including several arthroscopic imaging techniques and standardized gait analysis. In Part III, reinforced GelMA was applied for the biofabrication of implants for the restoration of large joint defects. Anatomically-shaped, osteochondral implants were fabricated and further developed for the restoration of the complete shoulder joint in rabbits. A pilot study on the strength and fixation of the implants in ongoing in three rabbits. Altogether, in this thesis, biologically active implants have been biofabricated with an imposed internal organization and external architecture. The regeneration of bone and cartilage tissue in these constructs was demonstrated in vitro and in ectopic locations in rodents. Large animal models were established and are currently conducted to evaluate the potential of these implants for the repair of focal or complete articular joint defects.