using-vertically-aligned-carbon-nanofiber-arrays-on-rigid-or-flexible

Using Vertically Aligned Carbon Nanofiber Arrays on Rigid or Flexible Substrates for Delivery of Biomolecules and Dyes to Plants

The delivery of biomolecules and impermeable dyes to intact plants is a major challenge. Nanomaterials are up-and-coming tools for the delivery of DNA to ...

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

Studying the formation and interactions between biological systems and artificial materials is significant for probing complex biophysical behaviors and addressing challenging biomedical problems. Bioelectrical interfaces, especially nanostructure-based, have improved compatibility with cells and tissues and enabled new approaches to biological modulation. In particular, free-standing and remotely activated bioelectrical devices demonstrate potential for precise biophysical investigation and efficient clinical therapies. Interacting with single cells or organelles requires devices of sufficiently small size for high resolution probing. Nanoscale semiconductors, given their diverse functionalities, are promising device platforms for subcellular modulation. Tissue-level modulation requires additional consideration regarding the device's mechanical compliance for either conformal contact with the tissue surface or seamless three-dimensional (3D) biointegration. Flexible or even open-framework designs are essential in such methods. For chronic organ integration, the highest level of biocompatibility is required for both the materials and device configurations. Additionally, a scalable and high-throughput design is necessary to simultaneously interact with many individual cells in the organ. The physical, chemical, and mechanical stabilities of devices for organ implantation may be improved by ensuring matching of mechanical behavior at biointerfaces, including passivation or resistance designs to mitigate physiological impacts, or incorporating self-healing or adaptative properties. Recent research demonstrates principles of nanostructured material designs that can be used to improve biointerfaces. Nanoenabled extracellular interfaces were frequently used for either electrical or remote optical modulation of cells and tissues. In particular, methods are now available for designing and screening nanostructured silicon, especially chemical vapor deposition (CVD)-derived nanowires and two-dimensional (2D) nanostructured membranes, for biological modulation in vitro and in vivo. For intra- and intercellular biological modulation, semiconductor/cell composites have been created through the internalization of nanowires, and such cellular composites can even integrate with living tissues. This approach was demonstrated for both neuronal and cardiac modulation. At a different front, laser-derived nanocrystalline semiconductors showed electrochemical and photoelectrochemical activities, and they were used to modulate cells and organs. Recently, self-assembly of nanoscale building blocks enabled fabrication of efficient monolithic carbon-based electrodes for in vitro stimulation of cardiomyocytes, ex vivo stimulation of retinas and hearts, and in vivo stimulation of sciatic nerves. Future studies on nanoenabled bioelectrical modulation should focus on improving efficiency and stability of current and emerging technologies. New materials and devices can access new interrogation targets, such as subcellular structures, and possess more adaptable and responsive properties enabling seamless integration. Drawing inspiration from energy science and catalysis can help in such progress and open new avenues for biological modulation. The fundamental study of living bioelectronics could yield new cellular composites for diverse biological signaling control. In situ self-assembled biointerfaces are of special interest in this area as cell type targeting can be achieved.

Nanoenabled Bioelectrical Modulation.

Homo- and heterojunctions play essential roles in semiconductor-based devices such as field-effect transistors, solar cells, photodetectors and light-emitting diodes. Semiconductor junctions have been recently used to optically trigger biological modulation via photovoltaic or photoelectrochemical mechanisms. The creation of heterojunctions typically involves materials with different doping or composition, which leads to high cost, complex fabrications and potential side effects at biointerfaces. Here we show that a porosity-based heterojunction, a largely overlooked system in materials science, can yield an efficient photoelectrochemical response from the semiconductor surface. Using self-limiting stain etching, we create a nanoporous/non-porous, soft-hard heterojunction in p-type silicon within seconds under ambient conditions. Upon surface oxidation, the heterojunction yields a strong photoelectrochemical response in saline. Without any interconnects or metal modifications, the heterojunction enables efficient non-genetic optoelectronic stimulation of isolated rat hearts ex vivo and sciatic nerves in vivo with optical power comparable to optogenetics, and with near-infrared capabilities.

Porosity-based heterojunctions enable leadless optoelectronic modulation of tissues.

In the dynamic biological system, cells and tissues adapt to diverse environmental conditions and form memories, an essential aspect of training for survival and evolution. An understanding of the biological training principles will inform the design of biomimetic materials whose properties evolve with the environment and offer routes to programmable soft materials, neuromorphic computing, living materials, and biohybrid robotics. In this perspective, we examine the mechanisms by which cells are trained by environmental cues. We outline the artificial platforms that enable biological training and examine the relationship between biological training and biomimetic materials design. We place emphasis on nanoscale material platforms which, given their applicability to chemical, mechanical and electrical stimulation, are critical to bridging natural and synthetic systems.

Nanoenabled Trainable Systems: From Biointerfaces to Biomimetics.

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-bioelectronics, which blend the precision of nanotechnology with the complexity of biological systems, are evolving with innovations such as silicon nanowires, carbon nanotubes, and graphene. These elements serve applications from biochemical sensing to brain-machine interfacing. This review examines nano-bioelectronics' role in advancing biomedical interventions and discusses their potential in environmental monitoring, agricultural productivity, energy efficiency, and creative fields. The field is transitioning from molecular to ecosystem-level applications, with research exploring complex cellular mechanisms and communication. This fosters understanding of biological interactions at various levels, such as suggesting transformative approaches for ecosystem management and food security. Future research is expected to focus on refining nano-bioelectronic devices for integration with biological systems and on scalable manufacturing to broaden their reach and functionality.

Beyond 25 years of biomedical innovation in nano-bioelectronics.

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.

Understanding and exploiting bioelectric signaling pathways and physicochemical properties of materials that interface with living tissues is central to advancing tissue regeneration. In particular, the emerging field of bioelectronics leverages these principles to develop personalized, minimally invasive therapeutic strategies tailored to the dynamic demands of individual patients. By integrating sensing and actuation modules into flexible, biocompatible devices, clinicians can continuously monitor and modulate local electrical microenvironments, thereby guiding regenerative processes without extensive surgical interventions. This review provides a critical examination of how fundamental bioelectric cues and physicochemical considerations drive the design and engineering of next-generation bioelectronic platforms. These platforms not only promote the formation and maturation of new tissues across neural, cardiac, musculoskeletal, skin, and gastrointestinal systems but also precisely align therapies with the unique structural, functional, and electrophysiological characteristics of each tissue type. Collectively, these insights and innovations represent a convergence of biology, electronics, and materials science that holds tremendous promise for enhancing the efficacy, specificity, and long-term stability of regenerative treatments, ushering in a new era of advanced tissue engineering and patient-centered regenerative medicine.

Bioelectric and physicochemical foundations of bioelectronics in tissue regeneration.

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.

ArticleTotal : 2	Year
Publication title Cited by 1	2023
Publication title	2025

Article	Year
Nanoenabled Bioelectrical Modulation. Accounts of materials research\| PubMed ID: 34723193	2021
Porosity-based heterojunctions enable leadless optoelectronic modulation of tissues. Nature materials\| PubMed ID: 35618824	2022
Nanoenabled Trainable Systems: From Biointerfaces to Biomimetics. ACS nano\| PubMed ID: 36516872	2022
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
Beyond 25 years of biomedical innovation in nano-bioelectronics. Device\| PubMed ID: 39119268	2024
Gold-modified nanoporous silicon for photoelectrochemical regulation of intracellular condensates. Nature nanotechnology\| PubMed ID: 40234705	2025
Bioelectric and physicochemical foundations of bioelectronics in tissue regeneration. Biomaterials\| PubMed ID: 40367812	2025
Bioelectronic Drug-free Control of Opportunistic Pathogens through Selective Excitability. Device\| PubMed ID: 40454232	2024

Pengju Li

Biography

JoVE Journal Publications

Other Publications