Electric field stimulation-responsive hydrogels for bone regeneration: from mechanisms to applications

The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases, with fractures and osteoporosis being prominent examples. Consequently, promoting bone regeneration is a crucial medical challenge that demands immediate attention. As early as the mid-20th century, researchers revealed that electrical stimulation could effectively promote the healing and regeneration of bone tissue. This is achieved by mimicking the endogenous electric field within bone tissue, which influences cellular behavior and molecular mechanisms. In recent years, electroactive hydrogels responsive to electric field stimulation have been developed and applied to regulate cell functions at different stages of bone regeneration. This paper elaborates on the regulatory effects of electrical stimulation on MSCs, macrophages, and vascular endothelial cells during the process of bone regeneration. It also involves the activation of relevant ion channels and signaling pathways. Subsequently, it comprehensively reviews various electric-field-responsive hydrogels developed in recent years, covering aspects such as material selection, preparation methods, characteristics, and their applications in bone regeneration. Ultimately, it provides an objective summary of the existing deficiencies in hydrogel materials and research, and looks ahead to future development directions.