Wu Xinhui, Wang Tianlong, Zhao Jinhui, Zhang Lei, Liu Zhiqing, Chen Yixing, Luo Yiping, Liu Yaqi, Chen Yan, Jiang Hui, Duolikun Dilixiati, Liu Junjian, Cao Wentao, Zheng Longpo
Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Department of Prosthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 201102, China.
Adv Sci (Weinh). 2025 Jul;12(27):e2504293. doi: 10.1002/advs.202504293. Epub 2025 Apr 28.
The repair of osteoporotic bone defects remains inadequately addressed, primarily due to a disruption in bone homeostasis, characterized by insufficient bone formation and excessive bone resorption. Current research either focuses on promoting bone formation or inhibiting bone resorption, however, the bone repair efficacy of these single-target therapeutic strategies is limited. Herein, a "two-way regulation" bone homeostasis strategy is proposed utilizing piezoelectric composite membranes (DAT/KS), capable of simultaneously regulating osteogenesis and osteoclastogenesis, with high piezoelectric performance, good biocompatibility, and excellent degradability, to promote bone regeneration under osteoporotic conditions. The DAT/KS membrane under ultrasound (US) treatment enables the controlled modulation of piezoelectric stimulation and the release of saikosaponin D (SSD), which promotes osteogenic differentiation while simultaneously inhibiting osteoclast differentiation and function, thereby effectively restoring bone homeostasis and enhancing osteoporotic bone repair. Mechanistic insights reveal the promotion of both canonical and non-canonical Wnt signaling in bone marrow mesenchymal stem cells (BMSCs), which determines their osteogenic differentiation fate, and the downregulation of the NF-κB signaling in bone marrow mononuclear macrophages (BMMs). This study presents optimized sono-piezoelectric biomaterials capable of bidirectionally regulating both osteogenic and osteoclastic differentiation, providing a new potential therapeutic approach for pathological bone injuries.
骨质疏松性骨缺损的修复仍未得到充分解决，主要原因是骨稳态受到破坏，其特征是骨形成不足和骨吸收过度。目前的研究要么侧重于促进骨形成，要么抑制骨吸收，然而，这些单靶点治疗策略的骨修复效果有限。在此，我们提出了一种“双向调节”骨稳态策略，利用具有高压电性能、良好生物相容性和优异降解性的压电复合膜（DAT/KS），能够同时调节成骨和破骨细胞生成，以促进骨质疏松条件下的骨再生。超声（US）处理下的DAT/KS膜能够可控地调节压电刺激并释放柴胡皂苷D（SSD），其促进成骨分化，同时抑制破骨细胞分化和功能，从而有效地恢复骨稳态并增强骨质疏松性骨修复。机制研究揭示了促进骨髓间充质干细胞（BMSC）中经典和非经典Wnt信号通路，这决定了它们的成骨分化命运，并下调骨髓单核巨噬细胞（BMM）中的NF-κB信号通路。本研究提出了能够双向调节成骨和破骨细胞分化的优化超声压电生物材料，为病理性骨损伤提供了一种新的潜在治疗方法。
