Farjaminejad Samira, Dingle Aaron M
Department of Health Services Research and Management, School of Health and Psychological Sciences, University of London, London, WC1E 7HU, UK.
Department of Surgery Division of Plastic Surgery, University of Wisconsin-Madison, Madison, WI, USA.
Bioelectron Med. 2025 Aug 8;11(1):18. doi: 10.1186/s42234-025-00180-x.
Bone regeneration is a complex biological process that involves the coordinated action of osteoblasts, osteoclasts, and mesenchymal stem cells (MSCs). While bone possesses an intrinsic ability to heal, large defects, delayed unions, and non-unions require advanced therapeutic interventions. Electrical stimulation (ES) has emerged as a promising strategy to enhance bone healing by modulating cellular activity, promoting osteogenic differentiation, and accelerating vascularization. This review explores the mechanistic role of bioelectrical cues in bone regeneration, emphasizing the influence of voltage-gated ion channels, particularly voltage-gated calcium channels (VGCCs), in transducing electrical signals into biochemical responses. Various types of ES modalities, including direct current (DC), capacitive coupling (CC), Pulsed Electromagnetic Field (PEMF), and piezoelectric stimulation, are evaluated for their effectiveness in clinical and preclinical applications. Additionally, the synergistic potential of ES when combined with biomaterials, stem cells, and growth factors is discussed. Despite promising results, challenges remain in translating preclinical findings to clinical applications, with key hurdles including standardization of treatment protocols, variability in patient responses, and regulatory constraints. Large-animal models have provided insights into the efficacy of ES-based therapies, but limitations in field penetration and treatment reproducibility hinder widespread adoption. Future advancements in bioelectronic medicine, smart scaffolds, and artificial intelligence (AI)-driven personalized therapies hold potential to optimize ES-based bone regeneration. Addressing current limitations through interdisciplinary research will be critical in establishing ES as a mainstream therapeutic approach in orthopedic and maxillofacial regenerative medicine.
骨再生是一个复杂的生物学过程，涉及成骨细胞、破骨细胞和间充质干细胞（MSC）的协同作用。虽然骨骼具有自我愈合的内在能力，但大的骨缺损、延迟愈合和不愈合需要先进的治疗干预措施。电刺激（ES）已成为一种有前景的策略，可通过调节细胞活性、促进成骨分化和加速血管生成来增强骨愈合。本文综述探讨了生物电信号在骨再生中的作用机制，强调电压门控离子通道，特别是电压门控钙通道（VGCC）在将电信号转化为生化反应中的影响。评估了各种类型的电刺激方式，包括直流电（DC）、电容耦合（CC）、脉冲电磁场（PEMF）和压电刺激在临床和临床前应用中的有效性。此外，还讨论了电刺激与生物材料、干细胞和生长因子联合使用时的协同潜力。尽管取得了令人鼓舞的结果，但将临床前研究结果转化为临床应用仍面临挑战，主要障碍包括治疗方案的标准化、患者反应的变异性和监管限制。大型动物模型为基于电刺激的治疗效果提供了见解，但场穿透和治疗可重复性的限制阻碍了其广泛应用。生物电子医学、智能支架和人工智能（AI）驱动的个性化治疗的未来进展有望优化基于电刺激的骨再生。通过跨学科研究解决当前的局限性对于将电刺激确立为骨科和颌面再生医学的主流治疗方法至关重要。
