Zhang Yuheng, Wang Yi, Zou Jiahu, Huang Jiandang, Zhong Qiang, Xu Yixin, Lei Mingyuan, Chen Rong, Wang Ding, Li Hao, Wang Hongyu, Wang Jian, Shi Zhanjun, Cheng Hao
Department of Orthopedic, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Mater Today Bio. 2026 Feb 11;37:102922. doi: 10.1016/j.mtbio.2026.102922. eCollection 2026 Apr.
Bone defects caused by trauma, infection, tumors, osteoporosis, and diabetes disrupt skeletal integrity and impair regeneration. The healing process involves inflammatory hematoma formation, callus development, and remodeling, coordinated by diverse cells and signaling pathways. Conventional grafts and inorganic implants are limited by donor scarcity, immune rejection, and low bioactivity, necessitating more effective repair strategies. Recently, multifunctional smart hydrogels have emerged as a frontier in bone regeneration due to their biocompatibility, tunable structure, and ability to integrate diverse functionalities. This review systematically summarizes recent advances in thermotherapy- and electrotherapy-stimulative hydrogels for bone defect repair. Photothermal and magnetothermal hydrogels provide controlled thermal stimulation to activate Wnt/β-catenin, HIF-1α, and heat shock protein pathways, thereby promoting osteogenesis, angiogenesis, and immune modulation while exhibiting antibacterial and antitumor effects. Conductive and piezoelectric hydrogels reconstruct the native bioelectric microenvironment of bone, enhancing cellular activity and matrix mineralization through electrical or mechanoelectrical coupling. Finally, the review discusses the current challenges, design considerations, and future perspectives of advanced hydrogel systems in bone regeneration.
由创伤、感染、肿瘤、骨质疏松症和糖尿病引起的骨缺损会破坏骨骼完整性并损害再生能力。愈合过程包括炎症性血肿形成、骨痂发育和重塑，由多种细胞和信号通路协调。传统的移植物和无机植入物受到供体稀缺、免疫排斥和低生物活性的限制，因此需要更有效的修复策略。最近，多功能智能水凝胶因其生物相容性、可调节结构以及整合多种功能的能力，已成为骨再生领域的前沿研究方向。本文综述系统地总结了用于骨缺损修复的热疗和电疗刺激水凝胶的最新进展。光热和磁热水凝胶提供可控的热刺激，以激活Wnt/β-连环蛋白、HIF-1α和热休克蛋白通路，从而促进成骨、血管生成和免疫调节，同时展现出抗菌和抗肿瘤作用。导电和压电水凝胶重建骨骼的天然生物电微环境，通过电耦合或机电耦合增强细胞活性和基质矿化。最后，本文综述讨论了先进水凝胶系统在骨再生中的当前挑战、设计考量和未来前景。
