Piezoelectric hydrogels empowering closed-loop smart medicine: from self-powered sensing to autonomous therapy

Closed-loop medicine is characterized not by a specific smart material, but by the integration of sensing and treatment processes.A complete feedback-controlled loop encompasses the acquisition, processing, and therapeutic intervention of physiological signals, as well as the evaluation of the response.For this purpose, piezoelectric hydrogels are promising because they can convert periodic biomechanical movements into electrical signals for self-powered sensing and, in some designs, localized actuation.We review the design, integration, and balance of materials, sensing, and therapeutic and self-powered actuation mechanisms, while distinguishing the self-powered transduction from true closed-loop control.Reported applications include the control of seizures, management of diabetes, and the therapeutic care of chronic wounds, with some representative studies reporting drug accumulation reductions of three orders of magnitude and achievement of greater than 95% closure of wounds.Although these results are promising, intrinsic challenges remain, such as the lack of feedback assurance, piezoelectric hydrogels' long-term stability during implantation, immunocompatibility, and large-scale manufacturing, and standardized assessments.Programmable hydrogel networks combined with artificial intelligence may enable more autonomous therapeutic decisions in the future.For these reasons, we classify these piezoelectric hydrogel platforms as open-loop, semi-closed-loop, or fully autonomous systems based on the degree of integration of the sensing, processing, and decision-making, as well as the therapeutic intervention and feedback systems.This systems-level perspective may provide some insights into the potential of piezoelectric hydrogels for closed-loop medicine systems.