Injectable MSC Spheroid and Microgel Granular Composites for Engineering Cartilage Tissue

Abstract Articular cartilage is important for joint function, yet it can be damaged due to disease or trauma. Cartilage lacks natural healing processes and current clinical treatments are limited in their ability to form functional cartilage for repair. Here, we reimagine cartilage tissue engineering with an approach that combines aggregates of adult MSCs (spheroids) with hydrogel microparticles (microgels) to form granular composites that are injectable, permit cell-cell contacts for chondrogenesis, allow spheroid fusion and growth, and undergo interparticle crosslinking post-injection via light for stability. We use simulations and experimental analyses to establish the importance of initial MSC spheroid to microgel volume ratios in granular composites that balance mechanical support with tissue growth. Long-term chondrogenic cultures of granular composites produce engineered cartilage tissue within the range of native properties, which can be further enhanced via MSC/chondrocyte co-cultures. Altogether, we have developed a new strategy of injectable granular composites for engineering cartilage tissue.