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The current key challenge lies in the difficulty of achieving synergistic intervention for both excessive inflammation in the acute phase and the lack of neural structure during the repair phase. Accordingly, this study constructs an IL\u201010\u2010engineered injectable short fiber (IL10\u2010mPDA@SF) system based on immune\u2010structure synergistic regulation to promote peripheral nerve repair and suppress acute and chronic postoperative pain. On one hand, IL10\u2010mPDA@SF achieves immune regulation by locally and continuously releasing IL\u201010, which effectively induces macrophage polarization toward the M2 phenotype by activating macrophage surface receptors. This remodels the anti\u2010inflammatory microenvironment and blocks neuronal hyperexcitability. On the other hand, its extracellular matrix (ECM)\u2010like short fiber structure provides physical guidance for the directional migration of Schwann cells and the orderly regeneration of nerve axons, thereby inhibiting the traumatic neuroma formation and achieving guided neural structural regeneration. In vitro\u00a0experiments demonstrate the effectiveness of this dual\u2010modal synergistic mechanism. In a mouse plantar incision model, local injection of IL10\u2010mPDA@SF significantly reduces the acute mechanical hypersensitivity threshold by over 50%, promotes the repair of nerve function and wounds, and suppresses traumatic neuroma occurrence.<\/jats:p>","DOI":"10.1002\/smll.202508780","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:29:46Z","timestamp":1763368186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Promoting Nerve Regeneration via Injectable Immune\u2010Engineered Short\u2010Fibers for Prevent Postoperative Pain"],"prefix":"10.1002","volume":"22","author":[{"given":"Tingting","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Zhongshan Hospital Shanghai Key Laboratory of Perioperative Stress and Protection Fudan University  180 Fenglin Road Shanghai 200030 P. R. 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