Yang Jinghong, Li Runli, Wang Xiaoshuang, Lu Dongheng, Li Weichang, Wang Yan
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, China.
J Nanobiotechnology. 2025 Sep 3;23(1):603. doi: 10.1186/s12951-025-03653-y.
Irregular alveolar bone defects pose persistent clinical challenges due to their complex morphology and the lack of biomaterials that simultaneously provide structural integrity, biocompatibility, and dynamic osteoinductive potential. Herein, we report a fiber-reinforced, dual-network hydrogel system (OHADN fiber@Yoda1 hydrogel) engineered to recapitulate mechanobiological cues for enhanced bone regeneration. This injectable hydrogel integrates oxidized hyaluronic acid (OHA) crosslinked with Yoda1-loaded PLGA-collagen fiber fragments and stabilized via catechol-Fe³⁺ coordination, forming a robust and self-healing structure. The fiber network enhances matrix stiffness and sustains Yoda1 release, promoting PIEZO1 activation in stem cells and enabling persistent mechanotransduction. In vitro, this system effectively regulates macrophage polarization, maintains cellular tension homeostasis, and significantly upregulates osteogenic markers via the PIEZO1-ITGα5 axis. Transcriptomic profiling and mechanistic validation revealed that focal adhesion and cytoskeletal signaling pathways are enriched upon hydrogel treatment. In a rat alveolar bone defect model, the OHADN fiber@Yoda1 hydrogel demonstrated superior bone volume restoration and trabecular architecture compared to conventional materials. This work presents a promising paradigm for spatiotemporal control of osteoimmune microenvironments through mechanoresponsive biomaterials.
不规则的牙槽骨缺损因其复杂的形态以及缺乏能同时提供结构完整性、生物相容性和动态骨诱导潜能的生物材料而给临床带来持续挑战。在此，我们报告一种纤维增强双网络水凝胶系统（OHADN纤维@Yoda1水凝胶），其设计用于重现机械生物学线索以促进骨再生。这种可注射水凝胶整合了与负载Yoda1的PLGA - 胶原纤维片段交联并通过儿茶酚 - Fe³⁺配位稳定的氧化透明质酸（OHA），形成了坚固且可自我修复的结构。纤维网络增强了基质刚度并维持Yoda1释放，促进干细胞中PIEZO1的激活并实现持续的机械转导。在体外，该系统有效调节巨噬细胞极化，维持细胞张力稳态，并通过PIEZO1 - ITGα5轴显著上调成骨标志物。转录组分析和机制验证表明，水凝胶处理后粘着斑和细胞骨架信号通路富集。在大鼠牙槽骨缺损模型中，与传统材料相比，OHADN纤维@Yoda1水凝胶显示出更好的骨体积恢复和小梁结构。这项工作通过机械响应性生物材料为骨免疫微环境的时空控制提供了一个有前景的范例。
