Electrical stimulation system based on electroactive biomaterials for bone tissue engineering

Traumatic injuries can lead to large bone defects under extreme conditions, which usually take a long recovery period, while the prognosis is poor. Endogenous electric field, as one major biophysical cue, plays a critical role in regulating bone homeostasis and regeneration. Thus, electrical stimulation (ES) has been considered a promising external intervention to accelerate bone defect healing. In this review, we first introduce the endogenous bioelectrical signaling in bone tissue and cellular behaviors including adhesion, proliferation, arrangement, migration, and differentiation of bone-related cells in response to ES. Then, we will provide an overview of the latest progress in the field of electroactive biomaterials (EABMs), with a specific emphasis on conductive materials (carbon-based materials, conducting polymers, metallic nanomaterials, and MXenes) and piezoelectric materials, including piezoelectric ceramics and piezoelectric polymers. This comprehensive review will highlight the significant contributions of these materials to various aspects of the bone healing process, including osteogenesis, chondrogenesis, angiogenesis, antibacterial properties, and drug delivery. Afterwards, we overview the implementation of exogenous ES signals, by either invasive or non-invasive mode, and self-powered stimulation systems, such as piezoelectric, triboelectric, and photovoltaic cells-based nanogenerators, for bone tissue engineering (BTE). Noteworthily, we also discuss the underlying mechanism of ES-induced cellular response and summarize the related signaling pathways. Finally, the future development direction of applying the ES system based on EABMs for BTE is proposed.