Neuroengineering and Bioelectronics for Advanced Healthcare Materials
Authors: Philipp Gutruf, Róisín M. Owens, Anna Maria Pappa, John A Rogers
Journal: Advanced Healthcare Materials (2024)

Recent advances in neural interface technology and electrode development have significantly contributed to the fields of neuroscience and biomedical engineering. Key findings from a series of original as well as review and perspective articles highlighted in this special edition expand knowledge on the topics of neural modulation, safety, and electrode performance. Materials innovation can facilitate progress in neural engineering. An example is by Wang et al. (article 202302330), who demonstrated the potential of photothermal modulation using 2D materials, Ti3C2Tx Mxene, to excite neurons with high spatial and temporal precision. This study evaluates the biosafety of Ti3C2Tx-based photothermal modulation across multiple assays, including assessments of plasma membrane integrity, mitochondrial stress, and oxidative stress. The findings reveal that culturing neurons on Ti3C2Tx films and applying laser pulses with incident energy from 2 to10 mW per pulse does not damage the cell membrane, induce cellular stress, or generate oxidative stress; and therefore, establishes a safe operational range for photothermal modulation using Ti3C2Tx. A mechanically deployable approach presented by Terenzi et al. (article 202303812) engineers lipid-based pop-up conductive interfaces using conducting polymers and light-responsive azopolymer films. These interfaces offer dynamic and responsive neural interfaces that can be controlled through external stimuli, such as light. Electrically conducting polymers, summarized by Cuttaz et al. (article 202304447), are another capable class of materials, that present new opportunities in the design and fabrication of next generation electrodes for bidirectional skin interfacing. Conducting polymers rely on doping to exhibit electrical conductivity; however, depending on the type of doping, this can sometimes pose challenges in terms of stability, but also, unique opportunities in their design versatility and tunability, as thoroughly explained by Fidanovski at al. (article 202302354). In fact, through rational material design, materials can exhibit stretchability, self-healing ability, biocompatibility, breathability, and biodegradability—the five essential functionalities for skin-like biointegrated electronics, as discussed by Oh et al. (article 202303797). Further development in organ interfaces is showcased by Rauhala et al. (article 202302613), that demonstrates an E-Suture, a mixed-conductor based medical device. This suture integrates electronic functionality into traditional surgical sutures, enabling real-time monitoring and stimulation at the site of implantation, with demonstrations in electrophysiological recording in the central and peripheral nervous system. The concept of soft electronic neural interfaces is also explored in the context of Ma et al.'s work (article 202304164) that introduces high-density, conformable conducting polymer-based implantable neural probes for the developing brain. These probes are designed to adapt to the dynamic environment of the developing brain, ensuring stable and high-quality neural recordings over extended periods. Notably, for precision bioelectronics, integration of thermofluidic designs is an option to align device precision with the bodily fluids and the complexity of biological structures, as discussed by Jingcheng Ma et al. (article 202302431), in their perspective. Precision is key, for example, in applications where controlled and targeted drug delivery is required, offering benefits such as fewer side effects, reduced toxicity, and optimized dosages. Recent breakthroughs in soft, flexible, and adaptable bioelectronic micro-systems have enabled electronically controlled drug delivery with extreme precision in the brain, as summarized by Mariello et al. (article 202302969). The electrode–tissue interface is another critical aspect ensuring stability, precision, and sensitivity. As thoroughly investigated by Gryszel et al. (article 202302400), the volumetric capacitance created through reactive Pt sputtering is shown to result in high surface area electrodes. These electrodes exhibit enhanced capacitance and improved performance for neural recording and stimulation applications. Another electrode performance deep dive is performed in a study by Lewis et al. (article 202303401) that systematically investigates recording quality relative to electrode impedance, emphasizing the importance of optimizing electrode impedance to achieve good quality neural recordings. Alongside investigating new materials and optimizing the critical material– tissue interface, developing multi-modal methods to better understand and evaluate those technologies is crucial. Yang et al. (article 202302362) showcases an integrated microprism and microelectrode array for simultaneous electrophysiology and two-photon imaging across cortical layers. This technology enables the concurrent monitoring of neural activity and high-resolution imaging, offering a comprehensive tool for studying complex brain functions and diseases. The work by Kumari et al. (article 202302871) on multiscale modeling of magnetoelectric nanoelectrodes for the analysis of spatially selective neural stimulation provides a comprehensive framework for understanding and optimizing the spatial selectivity of neural stimulation techniques. This modeling approach aids in the design of more effective and targeted neural interface devices. Despite major technological advances, when it comes to implantables (e.g., intracranial bioelectronics), challenges remain, especially for clinical translation; for example, for the treatment of brain tumor or epilepsy, as discussed by Yoo et al. (article 202303563). In clinical settings, primarily wire-based techniques are used, associated with complications such as increased risk of infection. Wireless neuromodulation techniques, including opto–mechano- and magneto–electronics, as well as self-powered devices coupled with materials advances, can synergistically provide a new avenue for clinical translation described by Wang et al. (article 202303316). Another important aspect for the diagnosis and treatment of neurological disorders, as well as the exploration of brain neural circuit functionality, is adaptive sensing/ modulation, that is, systems that generate or detect signals and subsequently utilize them to interact with cells, tissues, and networks for closed-loop interrogation, as explained by Li et al. (article 202303289). Of relevance to that, is neuroprostheses, aiming to restore sensory, motor, and cognitive functions in disabled people. Re-establishing the connection between transplanted organs and the nervous system via optimizing the implantation type, location, and the closed-loop control algorithms will open-up new avenues in neuroprosthetics, as reviewed by Micera et al. (article 202302896). These studies collectively push the boundaries of current neural interface technologies, offering new insights and tools for the modulation, recording, and stimulation of neural activity. They pave the way for the development of more sophisticated and integrated biomedical devices that can improve our understanding of neural function and treatment of neurological disorders. Philipp Gutruf is an associate professor in the Biomedical Engineering Department at the University of Arizona. He received his postdoctoral training at Northwestern University and received his Ph.D. in 2016 at the RMIT University (Australia). His research group focuses on creating devices that intimately integrate with biological systems by combining innovations in soft materials, photonics, and electronics to create systems with broad impact on health diagnostics, therapeutics, and mechanistic insight. Róisín M. Owens is Professor of Bioelectronics at the Dept. of Chemical Engineering and Biotechnology at the University of Cambridge and Fellow of Newnham College. She is the deputy head of the School of Technology at Cambridge, in charge of research and strategy. With her group, she studies the integration of electronic devices with biological systems for continuous monitoring, from cell membranes to tissues and organs, with a particular interest in studying the microbiome–gut–brain axis. Anna-Maria Pappa is an assistant professor in the Department of Biomedical Engineering at the Khalifa University. Prior to this appointment, Anna-Maria held the Oppenheimer postdoctoral fellowship in Cambridge University and the Maudslay Butler fellowship in Pembroke College, Cambridge. She received her PhD in Bioelectronics in 2017, from the Ecole des Mines De St Etienne, France. Anna-Maria is currently leading the Bioelectronics and Biosensors on chip group (LAB-BBC), combining synthetic biology with bioelectronics toward point-of-care biosensors for health diagnostics and drug discovery. John A. Rogers is professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery at Northwestern University, where he is also director of the Querrey/Simpson Institute for Bioelectronics. He was an undergraduate, a Ph.D. student, and postdoctoral fellow at the University of Texas at Austin, MIT, and Harvard, respectively. He spent time at Bell Laboratories and the University of Illinios at Urbana/Champaign before joining Northwestern in 2016. His research interests connect engineering science and medical science. He is a member of the National Academy of Engineering, National Academy of Sciences, and National Academy of Medicine.