Construction of naturally derived hydrogels containing anti-inflammatory melittin for sustained drug delivery to treat osteoarthritis disease

Osteoarthritis (OA) has become a common degenerative joint disease, lacking clinical means to alleviate this disease. Melittin, taken from natural honeybee venom, possesses outstanding anti-inflammatory properties and has great potential to treat OA. However, its high toxicity and hemolytic properties limit its application. In this work, a biocompatible hydrogel was prepared from extracellular matrix (ECM) of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of ECM hydrogel loaded with melittin can reduce the intrinsic toxicity of melittin and prolong the release behavior, simultaneously. The<i>in vitro</i>study demonstrated that melittin-hydrogel could effectively inhibit phosphorylation-ERK/JNK, prevent the exacerbation of TNF-<i>α</i>-induced apoptosis in ATDC5 cells, and reduce their inflammatory markers, effectively alleviating OA and preventing cartilage degradation. Subsequently,<i>in vivo</i>studies have demonstrated that injecting melittin-hydrogel into the joint cavity of OA mice can effectively reduce cartilage degeneration. These findings suggest that melittin-hydrogel plays a critical role in the development of OA and may provide a therapeutic option for the treatment of OA disease.