Biomimetic melatonin-loaded silk fibroin/GelMA scaffold strengthens cartilage repair through retrieval of mitochondrial functions

Articular cartilage injury induced by collision or trauma is a common sports-related condition that may progress to pain,dysfunction,and secondary osteoarthritis(OA).Limited by self-renewal potential,cartilage regeneration faces a quandary while bio-inspired novel strategies are urgently required.In this study,by a soft freezing method and surface modification technique,a multi-functional silk fibroin(SF)plus gelatin methacrylate(GelMA)scaffold laden with melatonin(MT)was prepared.SF-GelMA@MT scaffold demonstrated enhanced biomechanical characteristics and long-acting melatonin release.In vitro treatment with SF-GelMA@MT induced the synthesis of cartilage extracellular matrix(ECM)components.Mechanistically,sustained release of melatonin yielded robust chondroprotective effects via improving mitochondrial polarization and antioxidant properties.SF-GelMA@MT implantation boosted cartilage renascence in a full-thickness cartilage defect model via mitochondria-associated sirtuins 1(SIRT1)-superoxide dismutase 2(SOD2)signaling pathway in vivo.In summary,this research proposed a welldesigned bionic composite scaffold that promotes cartilage regeneration via mitochondrial function enhancement,which is of tremendous potential for cartilage tissue engineering.