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<p>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.</p> Graphical abstract <p></p>

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Mechanically tunable fiber-based hydrogel activates PIEZO1–integrin axis for enhanced bone repair

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月3日

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  • Jinghong Yang,
  • Runli Li,
  • Xiaoshuang Wang,
  • Dongheng Lu,
  • Weichang Li,
  • Yan Wang

摘要

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.

Graphical abstract