Enhancing regeneration and functionality of excitable tissues via integrating bioelectronics and bioengineered constructs

Abstract The inherent complexities of excitable cardiac, nervous, and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical, structural, and mechanical properties. Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors, tissue regeneration, and therapeutic efficacy for excitable tissues. This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues, considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems. We explore the synergistic effects of these electrical microenvironments, combined with structural and mechanical guidance, on the regeneration of excitable tissues using tissue engineering scaffolds. Additionally, the emergence of micro/nanoscale bioelectronics has significantly broadened this field, facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular, tissue, and organ levels. These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs. The integration of tissue engineering and bioelectronics promises optimal outcomes, highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues. Furthermore, we envision critical challenges in engineering the next-generation hybrids, focusing on integrated fabrication strategies, the development of ionic conductive biomaterials, and their convergence with biosensors.