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An adaptable MSC membrane fusogenicity technology is conceptualized for lipid raft\u2010mediated targeting ligand embedding by using toolkits of discoidal high\u2010density lipoprotein (HDL)\u2010containing biomimicking 4F peptides. According to the pathological clues of brain diseases, the vascular cell adhesion molecule 1 specialized VBP peptide is fused with 4F to assemble 4F\u2010VBP (HDL), which acts as a biobridge and transfers VBP onto the living cell membrane via lipid rafts for surface engineering of MSCs in suspension. When compared with the membrane\u2010modifying strategies of PEGylated phospholipids, 4F\u2010VBP (HDL) provides a 3.86 higher linkage efficiency to obtain MSCs<jats:sup>4F\u2013VBP(HDL)<\/jats:sup>, which can recognize and adhere to the inflammatory endothelium for efficient blood\u2013brain barrier crossing and brain accumulation. In APPswe\/PSEN1dE9 mice with Alzheimer's disease (AD), the transcriptomic analysis reveals that systemic administration of MSCs<jats:sup>4F\u2013VBP(HDL)<\/jats:sup> can activate pathways associated with neuronal activity and diminish neuroinflammation for rewiring AD brains. This customizable HDL\u2010mediated membrane fusogenicity platform primes MSC inflammatory brain delivery, which can be expanded to other disease treatments by simply fusing 4F with relevant ligands for living cell engineering.<\/jats:p>","DOI":"10.1002\/adma.202302367","type":"journal-article","created":{"date-parts":[[2023,8,5]],"date-time":"2023-08-05T21:49:00Z","timestamp":1691272140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Nanodisc\u2010Paved Biobridge Facilitates Stem Cell Membrane Fusogenicity for Intracerebral Shuttling and Bystander Effects"],"prefix":"10.1002","volume":"35","author":[{"given":"Yi","family":"Jin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University  Nanjing 210009 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