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Paradoxically, remote orthopedic trauma robustly accelerates distal skin repair, yet the systemic molecular mediators driving this \u201cbone\u2010skin crosstalk\u201d remain undefined, precluding its translation into non\u2010invasive therapies. Here, we establish that macroscopic bone fracture expedites diabetic wound healing through the systemic release of exosomal miR\u2010130b\u20103p, a potent orchestrator of coupled angiogenesis and neurogenesis. To recapitulate this physiological axis non\u2010invasively, we engineered a self\u2010assembling, cholesterol\u2010modified agomir\u2010130b\u20103p nanocomplex that could bypass endolysosomal degradation. For sustained spatial delivery, these carrier\u2010free nanoassemblies were incorporated into an in situ photocrosslinkable methacrylated collagen\/silk fibroin hydrogel, creating a bio\u2010instructive extracellular matrix that prolongs microRNA bioavailability. In streptozotocin\u2010induced diabetic mice, hydrogel\u2010mediated agomir delivery achieved 97.2% full\u2010thickness wound closure. Advanced volumetric light\u2010sheet imaging of chemically cleared whole\u2010mount skin confirmed the robust spatiotemporal reconstruction of deep vascular and neural networks. These findings decode a distinct exosome\u2010mediated inter\u2010organ repair mechanism and demonstrate that biomimetic microRNA nanoformulations can effectively translate systemic physiological cues into localized, high\u2010efficacy therapeutics for ischemic neuropathic wounds.<\/jats:p>","DOI":"10.1002\/advs.76500","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T22:19:10Z","timestamp":1783808350000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling Bone\u2010Skin Crosstalk Enables miRNA Nanoformulation for Cutaneous Neurovascular Reconstruction in Diabetic Mice"],"prefix":"10.1002","volume":"13","author":[{"given":"Tao","family":"Shen","sequence":"first","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu P. 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