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Conventional tissue\u2010engineering strategies often lack spatiotemporal responsiveness to the pathological microenvironment or require external power sources for electrical stimulation. Inspired by enzymatic biofuel cell technology, this study introduces a microenvironment\u2010responsive self\u2010powered MXene\u2010based electroactive hydrogel (sp\u2010MEH) that uniquely integrates cascade catalysis with endogenous current generation under diabetic conditions. Unlike previously reported conductive hydrogels or piezoelectric materials, sp\u2010MEH autonomously consumes excess glucose and ROS while simultaneously producing sustained electrical signals without external energy input. This dual functionality enables three synergistic therapeutic actions: remodeling of the pathological chemical microenvironment to promote anti\u2010inflammatory macrophage polarization, activation of voltage\u2010gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels and downstream CaMKII\/PKC pathways to enhance osteogenic differentiation, and interference with bacterial energy metabolism to achieve potent antibacterial effects. sp\u2010MEH significantly outperforms its non\u2010electroactive or randomly mixed counterparts in promoting the regeneration of infected diabetic bones, as validated in vitro and in vivo. This study establishes a paradigm for self\u2010powered, microenvironment\u2010adaptive biomaterials that convert pathological cues into therapeutic signals. Thus, it presents a transformative strategy for complex bone defect repair.\n                  <\/jats:p>","DOI":"10.1002\/adma.75222","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:22Z","timestamp":1790751382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microenvironment Responsive Self\u2010Powered Hydrogel for Electro\u2010Inspired Regeneration of Infectious Diabetic Bone Defects"],"prefix":"10.1002","author":[{"given":"Shuyao","family":"Liu","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu P. R. 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