Microenvironment Responsive Self-Powered Hydrogel for Electro-Inspired Regeneration of Infectious Diabetic Bone...

Hyperglycemia, excessive reactive oxygen species (ROS), and bacterial infection considerably hinder the regeneration of infected diabetic bone defects. Conventional tissue-engineering 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-responsive self-powered MXene-based electroactive hydrogel (sp-MEH) that uniquely integrates cascade catalysis with endogenous current generation under diabetic conditions. Unlike previously reported conductive hydrogels or piezoelectric materials, sp-MEH 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-inflammatory macrophage polarization, activation of voltage-gated Ca²⁺ channels and downstream CaMKII/PKC pathways to enhance osteogenic differentiation, and interference with bacterial energy metabolism to achieve potent antibacterial effects. sp-MEH significantly outperforms its non-electroactive 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-powered, microenvironment-adaptive biomaterials that convert pathological cues into therapeutic signals. Thus, it presents a transformative strategy for complex bone defect repair.