<p>Collagen-based hydrogels are promising scaffolds for regenerative medicine due to their inherent bioactivity and biocompatibility. However, their clinical translation is hindered by the trade-off between injectability and fibrillar structural fidelity. Herein, we present a dynamic collagen hydrogel via a stage-mimicking assembly strategy that decouples rapid in situ crosslinking from subsequent fibrillogenesis. Methacrylated collagen (ColMA) was first crosslinked with dithiothreitol (DTT) through a visible light-induced thiol-ene reaction, forming an amorphous gel within seconds (Stage Ⅰ). Upon physiological incubation, the system spontaneously reconstructed into a fibrous matrix (Stage Ⅱ) with tunable mechanics and redox activity. The formed collagen nanofibers recapitulated extracellular matrix features, supported cell adhesion and orderly migration, while DTT-derived thiol groups conferred reactive oxygen species (ROS) scavenging capacity. In a diabetic wound model, the fibrillar hydrogel significantly promoted wound closure and epithelial regeneration, outperforming non-fibrillar or non-antioxidant controls. Histological and transcriptomic analyses confirmed enhanced M2 macrophage polarization, integrin β1-mediated adhesion, and activation of redox-responsive and cell–matrix interaction pathways. This study provides a versatile injectable collagen platform that integrates structural biomimicry, dynamic remodeling, and redox modulation, demonstrating high potential for chronic wound repair and broader bioresponsive scaffold design.</p> Graphical Abstract <p></p>

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Stage-Mimicking Assembly Strategy Enables Processable and Biomimetic Collagen Nanofiber Materials

  • Jiaqi Qiu,
  • Shuo Ma,
  • Sujie Xie,
  • Runzhi Huang,
  • Songsong Shi,
  • Yuening Mai,
  • Shizhao Ji,
  • Changsheng Liu,
  • Xue Qu

摘要

Collagen-based hydrogels are promising scaffolds for regenerative medicine due to their inherent bioactivity and biocompatibility. However, their clinical translation is hindered by the trade-off between injectability and fibrillar structural fidelity. Herein, we present a dynamic collagen hydrogel via a stage-mimicking assembly strategy that decouples rapid in situ crosslinking from subsequent fibrillogenesis. Methacrylated collagen (ColMA) was first crosslinked with dithiothreitol (DTT) through a visible light-induced thiol-ene reaction, forming an amorphous gel within seconds (Stage Ⅰ). Upon physiological incubation, the system spontaneously reconstructed into a fibrous matrix (Stage Ⅱ) with tunable mechanics and redox activity. The formed collagen nanofibers recapitulated extracellular matrix features, supported cell adhesion and orderly migration, while DTT-derived thiol groups conferred reactive oxygen species (ROS) scavenging capacity. In a diabetic wound model, the fibrillar hydrogel significantly promoted wound closure and epithelial regeneration, outperforming non-fibrillar or non-antioxidant controls. Histological and transcriptomic analyses confirmed enhanced M2 macrophage polarization, integrin β1-mediated adhesion, and activation of redox-responsive and cell–matrix interaction pathways. This study provides a versatile injectable collagen platform that integrates structural biomimicry, dynamic remodeling, and redox modulation, demonstrating high potential for chronic wound repair and broader bioresponsive scaffold design.

Graphical Abstract