# Glycogen Hydrogel Loaded with Schistosoma japonicas Peptide SJMHE1 Improves Skin Wound Healing

## TL;DR

A new hydrogel containing a helminth-derived peptide improves skin wound healing by reducing inflammation and promoting tissue regeneration.

## Contribution

A novel glycogen-based hydrogel loaded with a Schistosoma japonicum peptide is developed for enhanced wound healing.

## Key findings

- SJMHE1-gel promotes collagen deposition, angiogenesis, and hair follicle regeneration in skin wound healing.
- The hydrogel suppresses inflammation and promotes M2 macrophage polarization.
- SJMHE1 activates TGF-β and VEGFA pathways to enhance cell migration and angiogenesis.

## Abstract

Current wound healing strategies must confront numerous challenges. Helminth-induced immunomodulation offers a promising therapeutic avenue for inflammatory diseases and injury repair. However, research on the role of helminths in damage recovery remains limited. We utilized glycogen—a naturally occurring biomaterial—to encapsulate SJMHE1, a bioactive peptide derived from Schistosoma japonicum, and successfully developed a facilely prepared hydrogel formulation denoted as SJMHE1-gel. The properties of SJMHE1-gel, its effect on cell activity, and its performance in a murine full-thickness skin defect model were evaluated. The glycogen-based hydrogel exhibited a uniform pore size, excellent biocompatibility, and sustained release of SJMHE1. Topical application of SJMHE1-gel enhanced collagen deposition, promoted angiogenesis, facilitated the regeneration of hair follicles and sebaceous glands, and accelerated full-thickness wound healing. SJMHE1-gel also promoted M2 macrophage polarisation and suppressed inflammatory cytokine expression both in vivo and in vitro. Mechanistically, SJMHE1-treated macrophages upregulate TGF-β, which in turn promotes the migration of L929 fibroblasts and human umbilical vein endothelial cells (HUVECs) via the Smad3 pathway. Neutralization of TGF-β attenuates phosphorylated Smad3 (p-Smad3) levels and impairs the migratory capacity of both fibroblasts and HUVECs. Additionally, SJMHE1-treated macrophages upregulate VEGFA, thereby enhancing angiogenic tube formation in HUVECs. This easy-to-prepare hydrogel can regulate macrophage polarization, inhibit inflammation, promote angiogenesis, and accelerate collagen deposition, acting across wound healing stages to provide a novel therapeutic strategy.