# Photocrosslinkable Chitosan Quaternary Ammonium Salt-Based Ternary Hydrogel with Fibroblast Growth Factor 21 for Diabetic Wound Healing

## TL;DR

A new hydrogel combining chitosan, gelatin, and collagen with FGF-21 was developed to improve diabetic wound healing by reducing inflammation and promoting tissue repair.

## Contribution

A novel ternary hydrogel with FGF-21 and antimicrobial properties was developed for diabetic wound healing.

## Key findings

- The hydrogel promoted anti-inflammatory macrophage polarization and fibroblast activity in vitro.
- In diabetic mice, the hydrogel accelerated wound closure and improved reepithelialization and angiogenesis.
- The composite material synergizes inflammation resolution, antimicrobial action, and mechanical support.

## Abstract

Diabetic wounds represent a critical public health challenge due to impaired healing processes driven by chronic inflammation, infection, and biomechanical deficiencies. Despite advances in wound dressings and negative-pressure therapy, current treatments often fail to provide sufficient mechanical support or to fully resolve inflammatory responses, resulting in prolonged ulceration and high risk of complications. To address these limitations, a photocrosslinkable chitosan quaternary ammonium salt (CQS) derivative (methacrylated CQS [CQS-MA]) was developed to accelerate gelation and improve structural integrity. We then used ultraviolet-initiated copolymerization of CQS-MA with gelatin methacrylate (GelMA) and type I collagen to fabricate a ternary composite hydrogel encapsulating fibroblast growth factor 21 (FGF-21), termed G/C-CS@FGF-21. This composite hydrogel synergistically combined FGF-21’s early-stage inflammation-resolving activity, CQS’s sustained antimicrobial function, GelMA’s tunable mechanical resilience, and collagen’s native cell-adhesive ligands, which could promote all phases of wound repair. In vitro, G/C-CS@FGF-21 promoted macrophage polarization toward the anti-inflammatory M2 phenotype and enhanced fibroblast proliferation and migration. In a full-thickness diabetic mouse wound-healing model, treatment with G/C-CS@FGF-21 accelerated wound closure by mitigating inflammation and promoting reepithelialization and angiogenesis. These findings suggest that the G/C-CS@FGF-21 hydrogel holds strong potential for future clinical translation in diabetic wound management.