bidirectional-electrical-optoelectronic-interfaces-healthy-ischemic

Bidirectional Electrical and Optoelectronic Interfaces in Healthy and Ischemic <em>Ex Vivo</em> Rat Hearts

Electrophysiological studies are pivotal in exploring interactions between materials and cardiac biointerfaces. Recent advancements have introduced ...

The University of Chicago

Different research fields in energy sciences, such as photovoltaics for solar energy conversion, supercapacitors for energy storage, electrocatalysis for clean energy conversion technologies, and materials-bacterial hybrid for CO fixation have been under intense investigations over the past decade. In recent years, new platforms for biointerface designs have emerged from the energy conversion and storage principles. This paper reviews recent advances in nano- and microscale materials/devices for optical and electrical biointerfaces. First, a connection is drawn between biointerfaces and energy science, and how these two distinct research fields can be connected is summarized. Then, a brief overview of current available tools for biointerface studies is presented. Third, three representative biointerfaces are reviewed, including neural, cardiac, and bacterial biointerfaces, to show how to apply these tools and principles to biointerface design and research. Finally, two possible future research directions for nano- and microscale biointerfaces are proposed.

Nano- and Microscale Optical and Electrical Biointerfaces and Their Relevance to Energy Research.

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.

Monolithic silicon for high spatiotemporal translational photostimulation.

Electrical neuromodulation has achieved significant translational advancements, including the development of deep brain stimulators for managing neural disorders and vagus nerve stimulators for seizure treatment. Optoelectronics, in contrast to wired electrical systems, offers the leadless feature that guides multisite and high spatiotemporal neural system targeting, ensuring high specificity and precision in translational therapies known as "photoelectroceuticals". This Account provides a concise overview of developments in novel optoelectronic nanomaterials that are engineered through innovative molecular, chemical, and nanostructure designs to facilitate neural interfacing with high efficiency and minimally invasive implantation.This Account outlines the progress made both within our laboratory and across the broader scientific community, with particular attention to implications in materials innovation strategies, studying bioelectrical activation with spatiotemporal methods, and applications in regenerative medicine. In materials innovation, we highlight a nongenetic, biocompatible, and minimally invasive approach for neuromodulation that spans various length scales, from single neurons to nerve tissues using nanosized particles and monolithic membranes. Furthermore, our discussion exposes the critical unresolved questions in the field, including mechanisms of interaction at the nanobio interface, the precision of cellular or tissue targeting, and integration into existing neural networks with high spatiotemporal modulation. In addition, we present the challenges and pressing needs for long-term stability and biocompatibility, scalability for clinical applications, and the development of noninvasive monitoring and control systems.In addressing the existing challenges in the field of nanobio interfaces, particularly for neural applications, we envisage promising strategic directions that could significantly advance this burgeoning domain. This involves a deeper theoretical understanding of nanobiointerfaces, where simulations and experimental validations on how nanomaterials interact spatiotemporally with biological systems are crucial. The development of more durable materials is vital for prolonged applications in dynamic neural interfaces, and the ability to manipulate neural activity with high specificity and spatial resolution, paves the way for targeting individual neurons or specific neural circuits. Additionally, integrating these interfaces with advanced control systems, possibly leveraging artificial intelligence and machine learning algorithms and programming dynamically responsive materials designs, could significantly ease the implementation of stimulation and recording. These innovations hold the potential to introduce novel treatment modalities for a wide range of neurological and systemic disorders.

Exploring Present and Future Directions in Nano-Enhanced Optoelectronic Neuromodulation.

Seamless interfaces between electronic devices and biological tissues stand to revolutionize disease diagnosis and treatment. However, biological and biomechanical disparities between synthetic materials and living tissues present challenges at bioelectrical signal transduction interfaces. We introduce the active biointegrated living electronics (ABLE) platform, encompassing capabilities across the biogenic, biomechanical, and bioelectrical properties simultaneously. The living biointerface, comprising a bioelectronics layout and a -laden hydrogel composite, enables multimodal signal transduction at the microbial-mammalian nexus. The extracellular components of the living hydrogels, prepared through thermal release of naturally occurring amylose polymer chains, are viscoelastic, capable of sustaining the bacteria with high viability. Through electrophysiological recordings and wireless probing of skin electrical impedance, body temperature, and humidity, ABLE monitors microbial-driven intervention in psoriasis.

Active biointegrated living electronics for managing inflammation.

Nano-enabled catalysis at the interface of metals and semiconductors has found numerous applications, but its role in mediating cellular responses is still largely unexplored. Here we explore the territory by examining the once elusive mechanism through which a nanoporous silicon-based photocatalyst facilitates the two-electron oxidation of water to generate hydrogen peroxide under physiological conditions. We achieve precise modulation of intracellular stress granule formation by the controlled photoelectrochemical production of hydrogen peroxide in the extracellular environment, thereby enhancing cellular resilience to significant oxidative stress. This photoelectrochemical strategy has been evaluated for its efficacy in treating myocardial ischaemia-reperfusion injury in an ex vivo rodent model. Our data suggest that a pretreatment regimen involving photoelectrochemical generation of hydrogen peroxide at mild concentrations mitigates myocardial ischaemia-reperfusion-induced functional decline and infarction. These findings suggest a viable wireless therapeutic intervention for managing ischaemic disease and highlight the biomedical potential of nanostructured semiconductor-based catalytic devices.

Gold-modified nanoporous silicon for photoelectrochemical regulation of intracellular condensates.

The natural excitability in mammalian tissues has been extensively exploited for drug-free electroceutical therapies. However, it is unclear whether bacterial residents on the human body are equally excitable and if their excitability can also be leveraged for drug-free bioelectronic treatment. Using a microelectronic platform, we examined the electrical excitability of , a skin-residing bacterium responsible for widespread clinical infections. We discovered that a non-lethal electrical stimulus could excite , inducing reversible changes in membrane potential. Intriguingly,  became excitable only under acidic skin pH, indicating that the bacteria were 'selective' about the environment in which they display excitability. This selective excitability enabled programmable suppression of biofilm formation using benign stimulation voltages. Lastly, we demonstrated suppression of  on a porcine skin model using a flexible electroceutical patch. Our work shows that the innate excitability of resident bacteria can be selectively activated for drug-free bioelectronic control.

Article	Year
Nano- and Microscale Optical and Electrical Biointerfaces and Their Relevance to Energy Research. Small (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 34142435	2021
Monolithic silicon for high spatiotemporal translational photostimulation. Nature\| PubMed ID: 38383782	2024
Exploring Present and Future Directions in Nano-Enhanced Optoelectronic Neuromodulation. Accounts of chemical research\| PubMed ID: 38652467	2024
Active biointegrated living electronics for managing inflammation. Science (New York, N.Y.)\| PubMed ID: 38815037	2024
Gold-modified nanoporous silicon for photoelectrochemical regulation of intracellular condensates. Nature nanotechnology\| PubMed ID: 40234705	2025
Bioelectronic Drug-free Control of Opportunistic Pathogens through Selective Excitability. Device\| PubMed ID: 40454232	2024

Chuanwang Yang

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