Multifunctional Biomimetic Nanomedicine for Osteoarthritis Alleviation by Mitigating Cartilage Degeneration and Promoting Cartilage Regeneration.

Osteoarthritis (OA) is a long-standing degenerative condition of the joints, defined by the progressive loss of articular cartilage accompanied by ongoing inflammation. For OA to be effectively treated, reducing cartilage breakdown and enhancing its regeneration are essential objectives. However, OA involves chronic sustained inflammation, making it difficult to protect cartilage and promote its regeneration under inflammatory conditions for effective OA treatment. To address these challenges, a kartogenin (KGN)-loaded biomimetic targeting system, designated CM@Lipos-KGN, was developed by integrating the anti-inflammatory properties of M2 macrophage membranes and the ability of KGN to promote chondrogenic differentiation of BMSCs. CM@Lipos-KGN was obtained by encapsulating KGN within liposomes coated with M2 macrophage cell membranes. It was found that CM@Lipos-KGN effectively protects cartilage in vitro by simultaneously suppressing inflammation and chondrocyte ferroptosis while maintaining chondrocyte metabolic homeostasis. Additionally, CM@Lipos-KGN significantly enhances the directional chondrogenic differentiation of BMSCs under inflammatory conditions in vitro, thereby facilitating cartilage regeneration. Animal experiments confirmed that CM@Lipos-KGN slowed the progression of OA and safeguarded cartilage by enhancing the expression of cartilage-associated proteins such as aggrecan and collagen II while simultaneously suppressing the levels of catabolic enzymes ADAMTS5 and MMP13. These findings underscore the considerable promise of CM@Lipos-KGN as a nanotechnology-based therapeutic platform for OA treatment.