Scaffold-free cartilage cell sheet combined with bone-phase BMSCs-scaffold regenerate osteochondral construct in mini-pig model

Tissue-engineered condyles provide a promising approach for end-stage osteoarthritis to reconstruct normal physiological structure and function of the temporomandibular joint (TMJ). However, lack of successful biological condyles in large animals restricts clinical translation. Scaffold-free cartilage cell sheets do not contain any polymeric material which potentially risks local nonspecific inflammatory reactions. In this study, we used cartilage cell sheets covering bone marrow mesenchymal stem cells-Polycaprolactone/Hydroxyapatite (BMSCs-PCL/HA) scaffolds (cell sheet group) transplanted subcutaneously and intramuscularly in mini-pigs. In contrast, autogenous chondrocytes were seeded on polyglycolic acid/ polylactic acid (PGA/PLA) scaffolds for 4 and 12 weeks in-vitro pre-cultivation. Then, they were used as a cartilage-phase composition covering BMSCs-PCL/HA scaffolds, then the entirety (biphase scaffold group) was transplanted subcutaneously into mini-pigs. After 12 weeks, the harvested samples were examined histologically. The cartilage layer was evaluated for thickness, glycosaminoglycan (GAG) quantitation, total collagen quantitation and Young’s modulus. The biphase scaffold group failed in regeneration, while the cell sheet group regenerated biological condyle with healthy osteochondral construct. The GAG quantitation, total collagen quantitation and Young’s modulus of regenerated cartilage was close to those of the natural condyle. Collectively, cartilage cell sheets combined with bone-phase composition had the potential to regenerate biological condylar.