BACKGROUND: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment.Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of longterm maintenance of efficacy. METHODS: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). RESULTS: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-a, IL-1b, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. CONCLUSION This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.

BACKGROUND: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment.Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of longterm maintenance of efficacy. METHODS: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). RESULTS: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-a, IL-1b, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. CONCLUSION This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.