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.

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Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

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Recent developments in optophysiology techniques such as optogenetics have revolutionized the ability to actuate cell activity. Further combining optophysiology and electrophysiology will integrate the advantages from both optical and electrical modalities and yield enabling technologies that allow simultaneous monitoring of cellular activity in response to modulation, which are crucial for biomedical applications. However, multifunctional devices that can deliver optical stimuli to regions beneath the electrodes and perform simultaneous sensing remain largely unexplored. Existing transparent microelectrode technologies depend on external bulk optical instruments for optical interventions. Here, innovative monolithic integrated multifunctional microsystems are demonstrated by applying transparent nanogrid electrodes onto microscale light sources to permit simultaneous electrophysiology and optical modulation at the same anatomical site. The nanogrid electrodes have transmittances > 70% with a low normalized impedance of 5.9 Ω cm2. Additional features of the devices include superior mechanical flexibility, minimized light‐induced electrical artifacts, and excellent biocompatibility. Ex vivo experiments demonstrate that the multifunctional devices can record abnormal heart rhythm in transgenic mouse hearts and simultaneously restore the sinus rhythm via optogenetic pacing. This work provides a versatile approach for constructing multifunctional colocalized biointerfaces containing crosstalk‐free optical and electrical modalities with expanded opportunities in both fundamental and applied biomedical research.

Transparent microelectrodes have recently emerged as a promising approach for crosstalk‐free multifunctional electrical and optical biointerfacing. High‐performance flexible platforms that allow seamless integration with soft tissue systems for such applications are urgently needed. Here, silver nanowires (Ag NWs)‐based transparent microelectrode arrays (MEAs) and interconnects are designed to meet this demand. The nanowire networks exhibit a high optical transparency >90.0% at 550 nm, and superior mechanical stability up to 100,000 bending cycles at 5 mm radius. The Ag NWs microelectrodes preserve low normalized electrochemical impedance of 3.4–15 Ω cm2 at 1 kHz, and the interconnects demonstrate excellent sheet resistance (Rsh) of 4.1–25 Ω sq−1. In vivo histological analysis reveals that the Ag NWs structures are biocompatible. Studies on Langendorff‐perfused mouse and rat hearts demonstrate that the Ag NWs MEAs enable high‐fidelity real‐time monitoring of heart rhythm during co‐localized optogenetic pacing and optical mapping. This proof‐of‐concept work illustrates that the solution‐processed, transparent, and flexible Ag NWs structures are a promising candidate for the next‐generation of large‐area multifunctional biointerfaces for interrogating complex biological systems in basic and translational research.

Flexible and transparent microelectrodes and interconnects provide the unique capability for a wide range of emerging biological applications, including simultaneous optical and electrical interrogation of biological systems. For practical biointerfacing, it is important to further improve the optical, electrical, electrochemical, and mechanical properties of the transparent conductive materials. Here, high‐performance microelectrodes and interconnects with high optical transmittance (59–81%), superior electrochemical impedance (5.4–18.4 Ω cm2), and excellent sheet resistance (5.6–14.1 Ω sq−1), using indium tin oxide (ITO) and metal grid (MG) hybrid structures are demonstrated. Notably, the hybrid structures retain the superior mechanical properties of flexible MG other than brittle ITO with no changes in sheet resistance even after 5000 bending cycles against a small radius at 5 mm. The capabilities of the ITO/MG microelectrodes and interconnects are highlighted by high‐fidelity electrical recordings of transgenic mouse hearts during co‐localized programmed optogenetic stimulation. In vivo histological analysis reveals that the ITO/MG structures are fully biocompatible. Those results demonstrate the great potential of ITO/MG interfaces for broad fundamental and translational physiological studies.

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