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

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机构: [1]Capital Med Univ, Beijing Tongren Hosp, Dept Foot & Ankle Surg, Beijing 100730, Peoples R China [2]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Traumatol & Orthopaed, Sch Med,Dept Orthopaed,Shanghai Key Lab Prevent &, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China
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关键词: cartilage senescence efferocytosis Hydrogel microspheres lesion-localized osteoarthritis

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

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出版当年[2023]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 2 区 纳米科技
最新[2023]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 2 区 纳米科技
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出版当年[2022]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

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第一作者机构: [1]Capital Med Univ, Beijing Tongren Hosp, Dept Foot & Ankle Surg, Beijing 100730, Peoples R China [2]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Traumatol & Orthopaed, Sch Med,Dept Orthopaed,Shanghai Key Lab Prevent &, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China
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