High-mobility network hydrogel microsphere system to combat chondrocyte senescence for enhanced cartilage repair and regeneration.

Cellular senescence plays a crucial role in the progression of various diseases, and targeting senescence is a potential therapeutic strategy for osteoarthritis (OA). However, the complex biomechanical environment surrounding chondrocytes significantly affects their senescence process. Currently, few biomaterials are available that have the ability to modulate stresses and counteract chondrocyte senescence. In this study, we used cationic liposomes as the core of the crosslinked structure of the hydrogel network through imine bonding to construct a high-mobility network hydrogel microsphere system (Res@Lipo@HMs). The deformability of liposomes endowed mobility to the crosslinked structure of the hydrogel network. This system not only enhanced joint lubrication through a rolling mechanism but also distributed mechanical stress on chondrocytes by increasing the elastic deformation capacity of the microspheres. Moreover, this approach delayed chondrocyte senescence, improved chondrocyte physiological function, and slowed down OA progression by enhancing mitochondrial function and inhibiting senescence pathways. This study offers new insights into antisenescence strategies for chondrocyte therapy.