Fiber‐Electrospun Hydrogel Therapy for DNP: A synergistic electrospun‐hydrogel composite for alleviating diabetic neuropathic pain via MMP9 regulation and sodium channel inhibition

Diabetic neuropathic pain (DNP) remains a significant challenge in diabetes care, and effective therapeutic strategies are urgently needed. This study introduces an innovative electrospinning‐hydrogel composite, Fiber‐SIN/Gel‐LidC, designed for the controlled and synergistic release of Sinomenine (SIN) and Lidocaine (Lid). Bioinformatics and network pharmacology analyses identified MMP9 as a key player in DNP alleviation. The composite, composed of SIN‐loaded fibers and Lid microcrystals, ensures sustained drug release over 7 days, demonstrating excellent biocompatibility. In vivo experiments on diabetic rats revealed significant improvements in thermal and mechanical pain thresholds, along with a reduction in sciatic nerve excitability. Additionally, the composite significantly attenuated neuroinflammation, neuronal apoptosis, and morphological damage. Mechanistic studies highlighted the neuroprotective effects of Fiber‐SIN/Gel‐LidC, particularly through the regulation of MMP9 and inhibition of sodium channels. These findings suggest that Fiber‐SIN/Gel‐LidC holds great potential as an innovative biomaterial‐based approach for managing DNP, offering promising therapeutic prospects for diabetic neuropathy.