Abstract
Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.
Highlights
Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics
Current methods to provide cardiac stimuli to small animal models almost exclusively feature a physical tether for electrical power supply and user control, thereby limiting investigations to anesthetized in vivo studies of immobilized animals
Devices that feature optogenetic interfaces to the heart are in their infancy, as most are derived from those employed for optogenetic techniques in the brain[9]
Summary
Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. We present a class of device that supports optical and electrical multisite stimulation in engineering designs that address these requirements, with formats that allow full subdermal implantation in small animal models such as rats and mice. The tether-free nature of such devices allows for paradigms with fully conscious, freely moving subjects, in isolation or in social groups
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