Engineering Electro-Regenerative Microenvironment for Bone Repair: Advances in Electroactive Biomaterials

As a quintessential hard tissue in human, bone represents a masterpiece of biomineralization, with mineralized collagen fibrils serving as its fundamental building blocks. During the natural repair processes of bone, endogenous bioelectric fields generated by mineralized collagen have been demonstrated to promote tissue regeneration by modulating cellular behaviors and signal transduction. Inspired by these physiological mechanisms, increasing research efforts have focused on engineering electroactive biomaterials to modulate local bioelectrical cues and establish regenerative microenvironments conducive to bone repair. In this context, we propose the concept of the electro-regenerative microenvironment (ERM), which emphasizes the regulation of interconnected biological processes, including antibacterial activity, immunomodulation, angiogenesis, neurogenesis, and osteogenesis, through bioelectrical cues mediated by electroactive biomaterials. This review first discusses the nature of endogenous electric fields in bone and the electroactive, electrosensitive, and electro-responsive properties of hard tissues. Electroactive biomaterials are then discussed according to their primary electrical functions, with a focus on conductive and piezoelectric materials, while also considering triboelectric and other relevant electroactive systems. Subsequently, the mechanisms by which these materials contribute to the establishment and regulation of the ERM are summarized. Emerging trends, future research directions, and clinical translational challenges are also discussed. Overall, this review highlights recent advances in electroactive biomaterials and provides insights for designing next-generation biomaterials that engineer ERM for bone repair.