Closed-Loop Bioelectronics: From Functional Materials to Autonomous Therapy

Closed-loop bioelectronic systems sense physiological signals, compute adaptive therapeutic decisions, then deliver precisely timed interventions without human oversight, meeting a clinical need that fixed-schedule treatments cannot address. Achieving this capability at clinical scale requires functional materials that form stable, mechanically matched interfaces with living tissue, sensing and actuation components operating across electrical, chemical, or optical modalities, alongside system architectures that integrate real-time feedback control with wireless autonomous operation within implantable form factors. This review traces recent advances along the complete closed-loop pipeline, from functional material families at its foundation, through the transducer technologies and control architectures that enable autonomous operation, to the clinical systems that validate therapeutic outcomes. Spanning neurological, cardiovascular, metabolic, and wound healing applications, closed-loop operation has advanced from preclinical proof-of-concept to human clinical validation, with commercially approved devices now operating across multiple disease domains. Chronic interface stability, the generalization of embedded machine learning beyond controlled experimental settings, and wireless power delivery at clinical tissue depths, alongside the regulatory complexity of next-generation adaptive combination products, constitute the defining challenges at the current frontier of the field.