Promoting Nerve Regeneration via Injectable Immune‐Engineered Short‐Fibers for Prevent Postoperative Pain

Abstract Perioperative peripheral nerve injury (PNI) and impaired repair constitute a common pathological mechanism triggering acute and chronic postoperative pain. 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‐10‐engineered injectable short fiber (IL10‐mPDA@SF) system based on immune‐structure synergistic regulation to promote peripheral nerve repair and suppress acute and chronic postoperative pain. On one hand, IL10‐mPDA@SF achieves immune regulation by locally and continuously releasing IL‐10, which effectively induces macrophage polarization toward the M2 phenotype by activating macrophage surface receptors. This remodels the anti‐inflammatory microenvironment and blocks neuronal hyperexcitability. On the other hand, its extracellular matrix (ECM)‐like 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 experiments demonstrate the effectiveness of this dual‐modal synergistic mechanism. In a mouse plantar incision model, local injection of IL10‐mPDA@SF significantly reduces the acute mechanical hypersensitivity threshold by over 50%, promotes the repair of nerve function and wounds, and suppresses traumatic neuroma occurrence.