Controlled Release of Human Dental Pulp Stem Cell‐Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis

Abstract Temporomandibular joint osteoarthritis (TMJOA) is a painful inflammatory condition that limits mouth opening. Cell‐derived exosomes, which have anti‐inflammatory effects, are emerging as a treatment for TMJOA. Injection of dental pulp stem cells (DPSCs), which secrete exosomes, can moderate tissue damage in a rat model of TMJOA. However, injected exosomes are quickly cleared, necessitating repeated injections for therapeutic efficacy. Here, vinyl sulfone‐modified hyaluronic acid (HA‐VS) hydrogels, suitable for encapsulating exosomes are formulated. HA‐VS hydrogels degrade in the presence of hyaluronidase and allow for the release of beads of similar size to exosomes over 3 to 6 days. In a rat model of TMJOA, injection of exosomes or exosomes within HA‐VS hydrogels significantly attenuated damage‐mediated subchondral bone loss as determined by micro‐computed tomography, and reduced inflammatory and tissue damage scores as assessed by histology. Overall, DPSCs‐derived exosomes attenuated joint damage, but treatment with exosomes within HA‐VS hydrogels shows additional protective effects on subchondral bone maintenance and integrity. These findings confirm the protective effects of DPSCs‐derived exosomes in moderating tissue damage in TMJOA and suggest that combining exosomes with HA hydrogels can further promote their therapeutic effects.