Intra-articular Injection of Chitosan-Based Supramolecular Hydrogel for Osteoarthritis Treatment

ABSTRACT

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.