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The previous studies found that lubrication supplementation is closely related to damaged matrix regeneration, but the lubrication structure is prone to disintegration and failure. Here, combining with microfluidic and photopolymerization strategies, a supramolecular lubricating hydrogel microsphere is constructed, which is medicated by dipalmitoylphosphatidylcholine (DPPC) liposomes as the core, a natural component in body fluids, and complexed with cartilage matrix\u2010binding peptide functionalized methacryloylated hyaluronan acid (WYR\u2010HAMA) as the photoinitiated site. The highly intermolecular ion\u2010dipole interaction between DPPC and WYR\u2010HAMA can form a dynamic supramolecular lubricating layer on the damaged matrix interfaces, where inflammatory factor inhibitors are coupled with DPPC liposomes via hydrophobic interaction to resist inflammatory transmission. Additionally, microspheres can autonomously regulate lubrication structure: in the early and middle stages, they can actively provide microscale lubrication (\u00b5 \u2248 0.04); in the late stage, the wear debris induced by endogenous enzymatic decomposition transmitted to provide nanoscale lubrication for the damaged matrix (\u00b5 \u2248 0.06). In vivo experiments demonstrate microspheres promoted efficient extracellular matrix synthesis and the autonomous release of lubrication factors at the cellular level. The developed bioplatform allowing cellular lubrication metabolism would provide a promising strategy for regenerating friction\u2010induced matrix damage.<\/jats:p>","DOI":"10.1002\/advs.202504319","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T01:51:09Z","timestamp":1752717069000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Supramolecular Lubricating Hydrogel Microspheres Reshape Damaged Matrix Regeneration"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9506-7616","authenticated-orcid":false,"given":"Hui","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 P. R. 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