Nanoenabled Bioelectrical Modulation

[Image: see text] 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.