Light-responsive biointerfaces have emerged as a powerful strategy for modulating cellular and tissue electrophysiology without genetic modification. Over the past decade, advances in nanomaterials, optoelectronic device architectures, and biointerface engineering have enabled the development of non-genetic photostimulation systems capable of converting optical energy into electrical, electrochemical, or ionic stimuli for controlling excitable biological systems. Recent studies have demonstrated diverse material platforms—including semiconductor nanowires, quantum dots, organic optoelectronics, and biomolecular assemblies—that enable efficient phototransduction at the nano-bio interface. At the device level, innovations in soft optoelectronic interfaces, photovoltaic implants, and flexible bioelectronic scaffolds have expanded photostimulation from single-cell modulation to organ-scale control. Concurrently, emerging strategies for spatial and spatiotemporal programming of optical stimulation are enabling increasingly precise and multiplexed control of biological circuits. These developments are now accelerating the translation of photostimulation technologies toward clinical applications, including retinal prostheses, cardiac pacing, and minimally invasive bioelectronic therapies. In this Perspective, we discuss recent progress in materials and device aspects of non-genetic photostimulation, advances in spatially programmable optical biointerfaces, and emerging translational pathways toward photoelectroceuticals. We further highlight future opportunities in engineered tissues, biomolecular optoelectronics, and programmable biointerfaces that may enable next-generation therapeutic systems integrating nanotechnology, bioelectronics, and regenerative medicine.

Engineered cells have opened up a new avenue for scientists and engineers to achieve specialized biological functions. Nanomaterials, such as silicon nanowires and quantum dots, can establish tight interfaces with cells either extra-or intracellularly, and they have already been widely used to control cellular functions. The future exploration of nanomaterials in cellular engineering may reveal numerous opportunities in both fundamental bioelectric studies and clinic applications. In this review, we highlight several nanomaterials-enabled non-genetic approaches to fabricating engineered cells. First, we briefly review the latest progress in engineered or synthetic cells, such as protocells that create cell-like behaviors from nonliving building blocks, and cells made by genetic or chemical modifications. Next, we illustrate the need for non-genetic cellular engineering with semiconductors and present some examples where chemical synthesis yields complex morphology or functions needed for biointerfaces. We then provide discussions in detail about the semiconductor nanostructure-enabled neural, cardiac, and microbial modulations. We also suggest the need to integrate tissue engineering with semiconductor devices to carry out more complex functions. We end this review by providing our perspectives for future development in non-genetic cellular engineering.

Bio-integrated materials and devices can blur the interfaces between living and artificial systems. Microfluidics, bioelectronics, and engineered nanostructures, with close interactions with biology at the cellular or tissue levels, have already yielded a spectrum of new applications. Many new designs emerge, including of organ-on-a-chip systems, biodegradable implants, electroceutical devices, minimally invasive neuro-prosthetic tools, and soft robotics. In this review, we highlight a few recent advances of the fabrication and application of smart bio-hybrid systems, with a particular emphasis on the three-dimensional (3D) bio-integrated devices that mimic the 3D feature of tissue scaffolds. Moreover, neurons integrated with engineered nanostructures for wireless neuromodulation and dynamic neural output are briefly discussed. We also discuss the progress in the construction of cell-enabled soft robotics, where a tight coupling of the synthetic and biological parts is crucial for efficient function. Finally, we summarize the approaches for enhancing bio-integration with biomimetic microand nanostructures.