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Electrical stimulation (ES) enhances bone repair, but its underlying mechanism remains elusive. This study presents a masticatory\u2010driven piezoelectric hydrogel that converts chewing motions into endogenous\u2010like ES, triggering on\u2010demand NPY condensate release to enhance regeneration, validated in rat critical\u2010sized defect models. NPY as a key mediator is identified: ES triggers its phase transition to activate osteogenic signaling. The engineered hydrogel generates &gt;20\u00a0mV\u00a0cm\n                    <jats:sup>\u22121<\/jats:sup>\n                    (exceeding the \u22652\u00a0mV\u00a0cm\n                    <jats:sup>\u22121<\/jats:sup>\n                    threshold for NPY liquid\u2010liquid phase separation, LLPS) under physiological chewing. ES induces NPY conformational rearrangement (N\u2010terminus buried) to activate Y2 receptors (Y2R) on periodontal ligand\u2010derived stromal cells (PDLSCs). Mechanistically, ES plus NPY condensate promotes osteogenic differentiation of PDLSCs through pAKT\u2010Runx2 signaling. In vitro, the hydrogel boosts PDLSCs osteogenesis by 2\u2010fold (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\n                    <jats:italic>0.001<\/jats:italic>\n                    ). In 4\u2010week and 12\u2010week rat mandibular bone defects, it yielded greater bone volume and higher density (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\n                    <jats:italic>0.01<\/jats:italic>\n                    ) vs. controls, with Y2R\u2010pAKT\u2010RUNX2 activation confirmed. This self\u2010powered strategy leverages mastication for targeted ES, offering a mechanism\u2010driven solution that addresses current limitations and holds clinical promise.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504780","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:31:31Z","timestamp":1769495491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Masticatory\u2010Driven Piezoelectric Hydrogels with Electrical Stimulation\u2010Triggered NPY Condensate for Mandibular Bone Regeneration"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiaoting","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Prosthodontics, School of Stomatology Capital Medical University  Beijing China"},{"name":"Laboratory of Oral Health and Homeostatic Medicine, School of Stomatology and Beijing Laboratory of Oral Health Capital Medical University  Beijing 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