Humidity-Gated Moisture-Electric Therapy via Dual-Modal Eelectrostimulation for Adaptive Bioelectronic Interventions.

Abstract

With the development of bioelectronic devices, achieving adaptive therapy in dynamic environments remains challenging. Traditional electrostimulation struggles with external power dependence, insufficient responsiveness, and lack of environmental adaptability. This study presents a humidity-responsive moisture-electric generator (MEG) that autonomously delivers dual-mode electrostimulation tailored to dynamic physiological environments, addressing a long-standing challenge in adaptive bioelectronic therapy. The MEG is engineered using 3D-printed nanocomposites integrating a hygroscopic PEDOT:PSS/graphene oxide core and a mechanically robust polycaprolactone structure, enabling humidity-gated voltage modulation. Under low-humidity conditions (<60% RH), the device generates subthreshold voltages (<500 mV) that activate transient receptor potential vanilloid-1 (TRPV1)-mediated calcium signaling, enhancing fibroblast migration, angiogenesis, and M2 macrophage polarization-leading to a 33.17% acceleration in wound healing. Conversely, in high-humidity tumor microenvironments (>95% RH), the MEG produces therapeutic voltages (>500 mV) that disrupt cytoskeletal integrity, improve chemotherapeutic drug penetration, and activate TNF-α/NF-κB signaling, resulting in immunogenic cell death and 88.34% tumor suppression. Transcriptomic analyses reveal distinct pathway engagement-calcium signaling dominates regenerative responses, while TNF cascades mediate antitumor immunity. This humidity-adaptive platform represents a closed-loop, self-powered therapeutic system that couples environmental sensing with intelligent bioelectronic output. Beyond its dual applications, the MEG introduces a transformative paradigm for autonomous, personalized medical intervention.