Delivery of dental pulp stem cells by an injectable ROS-responsive hydrogel promotes temporomandibular joint cartilage repair via enhancing anti-apoptosis and regulating microenvironment

Temporomandibular joint (TMJ) cartilage repair poses a considerable clinical challenge, and tissue engineering has emerged as a promising solution. In this study, we developed an injectable reactive oxygen species (ROS)-responsive multifunctional hydrogel (RDGel) to encapsulate dental pulp stem cells (DPSCs/RDGel in short) for the targeted repair of condylar cartilage defect. The DPSCs/RDGel composite exhibited a synergistic effect in the elimination of TMJ OA (osteoarthritis) inflammation via the interaction between the hydrogel component and the DPSCs. We first demonstrated the applicability and biocompatibility of RDGel. RDGel encapsulation could enhance the anti-apoptotic ability of DPSCs by inhibiting P38/P53 mitochondrial apoptotic signal in vitro. We also proved that the utilization of DPSCs/RDGel composite effectively enhanced the expression of TMJOA cartilage matrix and promoted subchondral bone structure in vivo. Subsequently, we observed the synergistic improvement of DPSCs/RDGel composite on the oxidative stress microenvironment of TMJOA and its regulation and promotion of M2 polarization, thereby confirmed that M2 macrophages further promoted the condylar cartilage repair of DPSCs. This is the first time application of DPSCs/RDGel composite for the targeted repair of TMJOA condylar cartilage defects, presenting a novel and promising avenue for cell-based therapy.