A bioinspired and high-strengthed hydrogel for regeneration of perforated temporomandibular joint disc: Construction and pleiotropic immunomodulatory effects

Due to the lack of an ideal material for TMJ (temporomandibular joint) disc perforation and local inflammation interfering with tissue regeneration, a functional TGI/HA-CS (tilapia type I gelatin/hyaluronic acid-chondroitin sulfate) double network hydrogel was constructed in this paper. It was not only multiply bionic in its composition, structure and mechanical strength, but also endowed with the ability to immunomodulate microenvironment and simultaneously induce in situ repair of defected TMJ discs. On the one hand, it inhibited inflammatory effects of inflammasome in macrophages, reduced the extracellular matrix (ECM)-degrading enzymes secreted by chondrocytes, reversed the local inflammatory state, promoted the proliferation of TMJ disc cells and induced fibrochondrogenic differentiation of synovium-derived mesenchymal stem cells (SMSCs). On the other hand, it gave an impetus to repairing a relatively-large (6 mm-sized) defect in mini pigs’ TMJ discs in a rapid and high-quality manner, which suggested a promising clinical application. • The bionic and functional TGI/HA-CS double network hydrogel had advantages in physical, chemical and mechanical properties. • It inhibited inflammatory effects of inflammasome and reduced secreted ECM-degrading enzymes, thus reversing the local inflammatory state. • It promoted proliferation of TMJ disc cells and induced fibrochondrogenic differentiation of SMSCs via direct and indirect ways.