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

Autor: Wei Xiong, Zeyu Han, Sheng‐Long Ding, Haoran Wang, Yawei Du, Wenguo Cui, Ming‐Zhu Zhang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 19, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202400345
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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