In Situ Remodeling of Efferocytosis via Lesion‐Localized Microspheres to Reverse Cartilage Senescence

• DOI: 10.1002/advs.202400345
• Publication Date: 2024-03-13T11:04:43Z
• Authors: Wei Xiong; Zeyu Han; Sheng‐Long Ding; Haoran Wang; Yawei Du; Wenguo Cui; Ming‐Zhu Zhang
• Keywords: efferocytosis; Chondrogenesis; Senescence

Abstract Efferocytosis, an intrinsic regulatory mechanism to eliminate apoptotic cells, will be suppressed due the delayed apoptosis process in aging‐related diseases, such as osteoarthritis (OA). In this study, cartilage lesion‐localized hydrogel microspheres are developed remodel situ efferocytosis reverse senescence and recruit endogenous stem cells accelerate repair. Specifically, aldehyde‐ methacrylic anhydride (MA)‐modified hyaluronic acid (AHM), loaded with pro‐apoptotic liposomes (liposomes encapsulating ABT263, A‐Lipo) PDGF‐BB, namely A‐Lipo/PAHM, prepared by microfluidic photo‐cross‐linking techniques. By a degraded porcine explant OA model, lesion location experiment illustrated that aldehyde‐functionalized promote affinity for cartilage. vitro data showed A‐Lipo induced of senescent chondrocytes (Sn‐chondrocytes), which can then phagocytosed macrophages, remodeling facilitated protection normal maintained chondrogenic differentiation capacity MSCs. vivo experiments confirmed localized reversed promoted repair OA. It is believed strategy great significance tissue regeneration diseases.