Immune-modulated adhesive hydrogel for enhancing osteochondral graft adhesion and cartilage repair

Osteochondral autograft transfer system (OATS) can effectively improve cartilage injuries by obtaining bone-cartilage grafts from healthy sites and implanting them into the defective areas. However, in up to 40 % of patients, the lack of a stable adhesive interface between the osteochondral graft and the normal tissue surface reduces the repair efficiency. In this work, we report an injectable and biocompatible poly (N-hydroxyethyl acrylamide-N-hydroxy succinimide)/Gelatin (PHE-Gel) hydrogel, featuring the instant formation of a tough bio-interface, which allows for robust adhesion with osteochondral grafts. Through physicochemical characterization, we found that a system composed of 10%PHE-Gel possesses superior interfacial toughness and excellent biocompatibility. In vitro, mechanistic studies and RNA-seq analysis had shown that 10%PHE-Gel promotes the expression of cartilage anabolic metabolism genes by upregulating the hypoxia-inducible factor alpha (HIF-α) signaling pathway and downregulating the tumor necrosis factor (TNF) signaling pathway. Dimethyloxalylglycine (DMOG) loaded liposome (DMOG-Lip) promotes the transition of M1 macrophages to M2 macrophages, shifting the microenvironment towards a pro-repair direction. Studies on a rabbit OATS model indicated that DMOG-Lip loaded 10%PHE-Gel (10%PHE-Gel@DMOG-Lip) effectively modulated the immune microenvironment, facilitated the repair of the hyaline cartilage, and inhibited further degeneration of cartilage. This composite hydrogel offers a promising solution for enhancing OATS repair in tissue engineering and has the potential to improve outcomes in cartilage restoration procedures.