This study investigates the remodeling of efferocytosis via lesion-localized microspheres to reverse cartilage senescence and promote cartilage repair in osteoarthritis (OA). The researchers developed hydrogel microspheres modified with aldehyde and methacrylic anhydride (MA) to target degraded cartilage. These microspheres, loaded with pro-apoptotic liposomes (A-Lipo) and PDGF-BB, were designed to recruit endogenous stem cells and induce apoptosis of senescent chondrocytes (Sn-chondrocytes). In vitro experiments demonstrated that A-Lipo induced apoptosis of Sn-chondrocytes, which were then phagocytosed by macrophages through efferocytosis. This process maintained the chondrogenic differentiation capacity of mesenchymal stem cells (MSCs) and protected normal chondrocytes. In vivo experiments using an ACLT-induced OA model confirmed that the lesion-localized hydrogel microspheres effectively reversed cartilage senescence, recruited stem cells, and promoted cartilage repair. The study highlights the potential of this approach for treating aging-related diseases by remodeling efferocytosis in situ.This study investigates the remodeling of efferocytosis via lesion-localized microspheres to reverse cartilage senescence and promote cartilage repair in osteoarthritis (OA). The researchers developed hydrogel microspheres modified with aldehyde and methacrylic anhydride (MA) to target degraded cartilage. These microspheres, loaded with pro-apoptotic liposomes (A-Lipo) and PDGF-BB, were designed to recruit endogenous stem cells and induce apoptosis of senescent chondrocytes (Sn-chondrocytes). In vitro experiments demonstrated that A-Lipo induced apoptosis of Sn-chondrocytes, which were then phagocytosed by macrophages through efferocytosis. This process maintained the chondrogenic differentiation capacity of mesenchymal stem cells (MSCs) and protected normal chondrocytes. In vivo experiments using an ACLT-induced OA model confirmed that the lesion-localized hydrogel microspheres effectively reversed cartilage senescence, recruited stem cells, and promoted cartilage repair. The study highlights the potential of this approach for treating aging-related diseases by remodeling efferocytosis in situ.