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A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing
Fan Zhang1,2,3, Haijuan Zhang1,2, Shengfu Wang1,2
1Department of Wound healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Nature Communications
|April 20, 2025
Summary
This study introduces a novel hydrogel that rapidly heals infected wounds without scarring. The F/R gel clears bacteria, reduces inflammation, and promotes tissue regeneration for scarless wound repair.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Wound Healing
Background:
- Rapid and scar-free wound repair is a critical challenge in regenerative medicine.
- Chronic infected wounds present complex barriers to effective healing and often result in scarring.
- Current treatments struggle to address infection, inflammation, and fibrosis simultaneously.
Purpose of the Study:
- To develop a phase-adaptive hydrogel (F/R gel) for integrated promotion of rapid re-epithelization and scar suppression in chronic infected wounds.
- To investigate the hydrogel's ability to eliminate bacterial biofilm and modulate the wound microenvironment.
- To assess the hydrogel's capacity for controlled release of therapeutic agents to enhance regeneration and prevent fibrosis.
Main Methods:
- Construction of a dynamically Schiff base-crosslinked hydrogel (F/R gel).
- Incorporation of ε-polylysine for antimicrobial activity against bacterial biofilm.
- Integration of ceria nanozyme to interrupt oxidative stress and inflammation.
- Co-loading of fibroblast growth factor and c-Jun siRNA in microcapsules for controlled release to promote healing and inhibit scarring.
Main Results:
- The F/R gel effectively eliminated multidrug-resistant bacterial biofilm in an infectious microenvironment.
- Ceria nanozyme release interrupted the oxidative stress-inflammation cycle, creating a pro-regenerative environment.
- Controlled release of fibroblast growth factor and c-Jun siRNA promoted neoangiogenesis and cell proliferation while suppressing c-Jun overexpression.
- Normal-like skin regeneration with no perceptible scars was observed in infected male mouse and female rabbit ear wound models.
Conclusions:
- The developed F/R gel provides a promising strategy for scarless wound repair by addressing infection, inflammation, and fibrosis.
- The phase-adaptive hydrogel integrates multiple therapeutic functions for enhanced regenerative outcomes.
- This approach emphasizes immunomodulatory and fibroblast subtype modulation for advanced wound healing applications.
