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However, traditional bone\u2010guiding 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\u2010PF@PPy), creating a \u201cmechanical\u2010electrical\u2010pharmaceutical coupling\u201d system. In a micromotion mechanical environment, Met\u2010PF@PPy converts mechanical energy into electrical signals, activating the electrochemical reduction of PPy and triggering stress\u2010responsive Met release. The generated electrical signals suppress inflammation through M1\u2010to\u2010M2 macrophage polarization and simultaneously enhance osteogenesis. Simultaneously, Met inhibits the NF\u2010\u03baB pathway to reduce pro\u2010inflammatory cytokines while activating the AMPK pathway to promote osteogenesis and angiogenesis. In a diabetic mouse femoral fracture model, Met\u2010PF@PPy significantly reduces inflammatory markers, enhances vascularization, and increases bone mineral density and bone volume fraction by over 30%. This \u201cforce\u2010electric\u2010drug coupling\u201d strategy provides an innovative approach for active regulation in diabetic fracture repair and offers a versatile platform for advancing piezoelectric materials in regenerative medicine.<\/jats:p>","DOI":"10.1002\/adma.202505061","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T03:33:34Z","timestamp":1746502414000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Micromotion\u2010Driven \u201cMechanical\u2010Electrical\u2010Pharmaceutical Coupling\u201d Bone\u2010Guiding Membrane Modulates Stress\u2010Concentrating Inflammation Under Diabetic Fractures"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-9977","authenticated-orcid":false,"given":"Junhao","family":"Sui","sequence":"first","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengchen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqi","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Health Sciences and Engineering University of Shanghai for Science and Technology  Shanghai 200093 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Health Sciences and Engineering University of Shanghai for Science and Technology  Shanghai 200093 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Maxillofacial\u2010Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology Shanghai Jiao Tong University  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuogui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-2764","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Changhai Hospital Affiliated to the Navy Military Medical University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30061-9"},{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4283-6"},{"key":"e_1_2_7_1_3","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0199"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30378-X"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.02.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3843"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14254"},{"key":"e_1_2_7_3_3","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3847"},{"key":"e_1_2_7_4_1","first-page":"2024","author":"Jeon H. 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