Open thoracic surgical implantation of cardiac pacemakers in rats.

Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.

A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy.

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.

Flexible and Transparent Metal Oxide/Metal Grid Hybrid Interfaces for Electrophysiology and Optogenetics.

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.