Soft Hypoxia-Adaptive Bioelectronics Integrating PEDOT:PSS/Polydopamine/Enzyme Biocomposites for Closed-Loop Therapeutics of Chronic Wounds

Adaptive bioelectronics that autonomously adjust to environmental changes represent an emerging paradigm, enabling reliable operation across diverse conditions. Hypoxic microenvironments are prevalent across numerous pathological conditions including chronic wounds, tumors, and ischemic tissues, creating a fundamental challenge: oxygen-dependent enzymatic biosensors fail precisely when monitoring is most critical, while oxygen deficiency simultaneously impairs tissue regeneration. We present a soft wireless Hypoxia-Adaptive Sensing and Therapeutic (HAST) system that maintains reliable biosensing functionality in oxygen-deficient environments through integrated oxygen management. Using engineered poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)/polydopamine (PDA)/enzyme biocomposites, HAST integrates multiplexed biosensing (glucose, uric acid, lactate) with dual-oxygen provision: wound exudate-triggered dissolved oxygen generation restores biosensor functionality while electrical stimulation promotes vascular regeneration for sustained tissue oxygenation. This hypoxia-adaptive design achieves about 10-fold biosensor sensitivity enhancement under oxygen-deficient conditions while promoting tissue repair. In preclinical diabetic wound models, HAST enabled accurate continuous monitoring with ∼30% accelerated wound closure, demonstrating environment-adaptive bioelectronics for precision medicine in oxygen-deficient pathological conditions.