Micromotion‐Driven “Mechanical‐Electrical‐Pharmaceutical Coupling” Bone‐Guiding Membrane Modulates Stress‐Concentrating Inflammation Under Diabetic Fractures

Abstract The use of piezoelectric materials to convert micromechanical energy at the fracture site into electrical signals, thereby modulating stress‐concentrated inflammation, has emerged as a promising treatment strategy for diabetic fractures. However, traditional bone‐guiding membranes often face challenges in diabetic fracture repair due to their passive and imprecise drug release profiles. Herein, a piezoelectric polyvinylidene fluoride (PVDF) fibrous membrane is fabricated through electrospinning and oxidative polymerization to load metformin (Met) into a polypyrrole (PPy) coating (Met‐PF@PPy), creating a “mechanical‐electrical‐pharmaceutical coupling” system. In a micromotion mechanical environment, Met‐PF@PPy converts mechanical energy into electrical signals, activating the electrochemical reduction of PPy and triggering stress‐responsive Met release. The generated electrical signals suppress inflammation through M1‐to‐M2 macrophage polarization and simultaneously enhance osteogenesis. Simultaneously, Met inhibits the NF‐κB pathway to reduce pro‐inflammatory cytokines while activating the AMPK pathway to promote osteogenesis and angiogenesis. In a diabetic mouse femoral fracture model, Met‐PF@PPy significantly reduces inflammatory markers, enhances vascularization, and increases bone mineral density and bone volume fraction by over 30%. This “force‐electric‐drug coupling” strategy provides an innovative approach for active regulation in diabetic fracture repair and offers a versatile platform for advancing piezoelectric materials in regenerative medicine.