The maturation state and density of human cartilage microtissues influence their fusion and development into scaled-up grafts

This study investigates how the maturation stage and initial density of human mesenchymal stem cell–derived cartilage microtissues influence their fusion dynamics and the functional development of scaled-up cartilage grafts. Less mature microtissues fused more rapidly and supported enhanced chondrogenesis, with increased sulphated glycosaminoglycan and collagen deposition and reduced mineralization. Increasing the number of microtissues per construct enabled the formation of clinically relevant graft sizes without compromising tissue phenotype. Large-scale constructs formed from thousands of microtissues exhibited robust fusion and cartilage-like composition, with no significant differences in tensile stiffness between static and dynamic culture conditions, demonstrating the feasibility of microtissue-based strategies for engineering functional cartilage grafts.