Hydrogels Derived from Native Decellularized Perichondrium for Chondrocyte Differentiation and Temporomandibular Joint Repair

Osteoarthritis (OA) is a degenerative joint disease that causes chronic pain, disability, and cartilage loss, yet there are no approved disease-modifying OA therapies. Decellularized extracellular matrix (dECM) hydrogels preserve the biochemical complexity of native tissue and offer a promising platform for cartilage repair, yet their development and application for OA treatments remain poorly understood. We previously identified the perichondrium-like fibrocartilage lining the temporomandibular joint (TMJ) condyle as a niche harboring fibrocartilage stem/progenitor cells that support cartilage homeostasis. Based on this discovery, we developed a decellularized perichondrium-derived hydrogel (d-PC hydrogel) from native TMJ tissue, characterized its rheological and biological properties, and assessed its regenerative capacity. Decellularized hydrogels were prepared from New Zealand white rabbit TMJ perichondrium (d-PC) and condylar cartilage (d-CC), evaluated via rheological testing, and tested for chondrogenic potential by seeding primary human perichondrial or chondrocyte cells onto hydrogels followed by implantation into nude mice. Unlike the d-CC hydrogel, the d-PC hydrogel demonstrated superior gel-like properties and induced fibrocartilage stem/progenitor cells to form cartilage in vivo. In a post-traumatic rabbit TMJ-OA model, monthly intra-articular injections of d-PC hydrogel significantly improved TMJ cartilage tissue architecture and reduced MMP13 expression compared to d-CC hydrogel- and PBS-treated groups. These findings identify the TMJ perichondrium as a source of the dECM hydrogel capable of supporting chondrogenesis and TMJ cartilage repair. In future studies, we will explore its utility as an organoid system or delivery platform for cell- and drug-based disease-modifying OA therapies.