Reinforced Bacterial Cellulose/GelMA-HAMA Bionic Cartilage Hydrogel with Spatiotemporal Delivery of Exosomes and BMSCs for Temporomandibular Joint Disc Regeneration.

Abstract

Cartilage regeneration, especially of the temporomandibular joint (TMJ) disc critical for chewing and speech, remains challenging. Key hurdles include its avascular, low-cell structure (impeding repair cell migration) and persistent post-injury compressive/shear stresses (damaging tissue and disrupting new formation). This study designed a sandwich composite hydrogel: GelMA/HAMA loaded with BMSCs, combined with a PVA-bacterial cellulose membrane carrying chondrocyte-derived exosomes. The membrane provides mechanical support and slowly releases exosomes to regulate BMSC proliferation/differentiation. Biomechanical analysis showed reduced stress concentration at perforation edges, protecting regeneration. In vitro experiments confirmed upregulated cartilage matrix genes (e.g., COL1A1, ACAN) in BMSCs. Implantation in a rabbit TMJ disc perforation model for eight weeks led to new cartilage-like tissue and successful repair. This system, optimizing mechanical microenvironment, regulating stem cell fate, and promoting matrix regeneration, offers a novel strategy for functional TMJ disc repair.