Mechanically tunable fiber-based hydrogel activates PIEZO1-integrin axis for enhanced bone repair
Jinghong Yang1, Runli Li1, Xiaoshuang Wang1
1Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, China.
Journal of Nanobiotechnology
|September 3, 2025
Summary
A new fiber-reinforced hydrogel promotes bone regeneration by activating stem cell mechanotransduction. This biomaterial enhances bone volume and structure in defect models, offering a promising approach for alveolar bone repair.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Alveolar bone defects present significant clinical challenges due to complex morphology.
- Existing biomaterials often lack the necessary structural integrity, biocompatibility, and osteoinductive potential for effective regeneration.
Purpose of the Study:
- To engineer a fiber-reinforced, dual-network hydrogel system capable of delivering mechanobiological cues for enhanced bone regeneration.
- To investigate the hydrogel's ability to promote stem cell activation and regulate the osteoimmune microenvironment.
Main Methods:
- Development of an injectable hydrogel (OHADN fiber@Yoda1 hydrogel) integrating oxidized hyaluronic acid (OHA), Yoda1-loaded PLGA-collagen fibers, and catechol-Fe³⁺ coordination.
- Assessment of hydrogel properties including stiffness, self-healing, and sustained Yoda1 release.
- In vitro studies on stem cell mechanotransduction (PIEZO1 activation), macrophage polarization, and osteogenic marker expression.
- In vivo evaluation in a rat alveolar bone defect model.
Main Results:
- The hydrogel system demonstrated robust structural integrity and self-healing properties.
- Sustained Yoda1 release activated PIEZO1 in stem cells, promoting persistent mechanotransduction and upregulating osteogenic markers via the PIEZO1-ITGα5 axis.
- In vitro studies showed regulation of macrophage polarization and cellular tension homeostasis.
- The hydrogel significantly improved bone volume restoration and trabecular architecture in a rat model compared to controls.
Conclusions:
- The fiber-reinforced, dual-network hydrogel system effectively recapitulates mechanobiological cues for bone regeneration.
- This mechanoresponsive biomaterial demonstrates potential for spatiotemporal control of the osteoimmune microenvironment.
- The developed hydrogel offers a promising therapeutic strategy for treating irregular alveolar bone defects.
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