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

Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young's moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa-over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices.

Achieving tissue-level softness on stretchable electronics through a generalizable soft interlayer design.

The use of bioelectronic devices relies on direct contact with soft biotissues. For transistor-type bioelectronic devices, the semiconductors that need to have direct interfacing with biotissues for effective signal transduction do not adhere well with wet tissues, thereby limiting the stability and conformability at the interface. We report a bioadhesive polymer semiconductor through a double-network structure formed by a bioadhesive brush polymer and a redox-active semiconducting polymer. The resulting semiconducting film can form rapid and strong adhesion with wet tissue surfaces together with high charge-carrier mobility of ~1 square centimeter per volt per second, high stretchability, and good biocompatibility. Further fabrication of a fully bioadhesive transistor sensor enabled us to produce high-quality and stable electrophysiological recordings on an isolated rat heart and in vivo rat muscles.

Bioadhesive polymer semiconductors and transistors for intimate biointerfaces.

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.

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.

One of the greatest obstacles to achieving implantable electronics with long-term functionality and minimized inflammatory reactions is the immune-mediated foreign-body response (FBR). Recently, semiconducting polymers with mixed electron-ion conductivity have been demonstrated as promising candidates to achieve direct electrical interfacing on bio-tissues. However, there is limited understanding of their immune compatibility in vivo, and strategies for minimizing the FBR through molecular design remain underexplored. Here we introduce a set of molecular design strategies for enhancing the immune compatibility of semiconducting polymers. Specifically, we show that selenophene, when incorporated in the backbone, can mitigate the FBR by suppressing macrophage activation. In addition, side-chain functionalization with immunomodulatory groups decreases the FBR further by downregulating the expression of inflammatory biomarkers. Together, our synthesized polymers achieve suppression of the FBR by as much as 68% (as indicated by the collagen density). In the meantime, these immune-compatible designs still provide a high charge-carrier mobility of around 1 cm V s. We anticipate that such immune-compatible design principles can be translated to a variety of conjugated polymers to suppress the FBR for implantable applications.

Immune-compatible designs of semiconducting polymers for bioelectronics with suppressed foreign-body response.

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
Achieving tissue-level softness on stretchable electronics through a generalizable soft interlayer design. Nature communications\| PubMed ID: 37495580	2023
Bioadhesive polymer semiconductors and transistors for intimate biointerfaces. Science (New York, N.Y.)\| PubMed ID: 37561870	2023
Exploring Present and Future Directions in Nano-Enhanced Optoelectronic Neuromodulation. Accounts of chemical research\| PubMed ID: 38652467	2024
Gold-modified nanoporous silicon for photoelectrochemical regulation of intracellular condensates. Nature nanotechnology\| PubMed ID: 40234705	2025
Immune-compatible designs of semiconducting polymers for bioelectronics with suppressed foreign-body response. Nature materials\| PubMed ID: 40247019	2025
Bioelectronic Drug-free Control of Opportunistic Pathogens through Selective Excitability. Device\| PubMed ID: 40454232	2024

Zhe Cheng

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