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Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators and cardiac pacemakers. However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges. Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common.
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Flexible Electro‐Optical Arrays for Simultaneous Multi‐Site Colocalized Spatiotemporal Cardiac Mapping and Modulation
Abstract Bioelectronic devices that allow simultaneous accurate monitoring and control of the spatiotemporal patterns of cardiac activity provide an effective means to understand the mechanisms and optimize therapeutic strategies for heart disease. Optogenetics is a promising technology for cardiac research due to its advantages such as cell‐type selectivity and high space‐time resolution, but its efficacy is limited by the insufficient number of modulation channels and lack of simultaneous spatiotemporal mapping capabilities in current implantable cardiac optogenetics tools available for in vivo investigations. Here, soft implantable electro‐optical cardiac devices integrating multilayered highly uniform arrays of transparent microelectrodes and multicolor light‐emitting diodes in thin, flexible platforms are designed for mechanically compliant high‐content high‐precision electrical mapping and single‐/multi‐site optogenetics and electrical stimulation without light‐induced artifacts. Systematic benchtop characterizations, together with ex vivo and in vivo evaluations on healthy and diseased small animal hearts and human cardiac slices demonstrate their functionalities in real‐time spatiotemporal mapping and control of cardiac rhythm and function, with broad applications in basic and ultimately clinical cardiology.
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- PAR ID:
- 10443502
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Optical Materials
- Volume:
- 10
- Issue:
- 23
- ISSN:
- 2195-1071
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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