Enzyme-crosslinked hyaluronic acid hydrogel scaffolds for BMSCs microenvironment and wound healing

Int J Biol Macromol. 2025 Jan 7:139566. doi: 10.1016/j.ijbiomac.2025.139566. Online ahead of print.

Abstract

Tissue engineering utilizing hydrogel scaffolds in combination with exogenous stem cells holds significant potential for promoting wound regeneration. However, the microenvironment provided by existing skin tissue engineering scaffold materials is often inadequate. Herein, we demonstrate an enzyme-crosslinked hyaluronic acid hydrogel to provide a growth microenvironment for exogenous bone marrow mesenchymal stem cells and promote acute wound healing. This material is developed by grafting dopamine onto hyaluronic acid, followed by enzyme crosslinking using horseradish peroxidase and hydrogen peroxide, which creates a loose, porous structure. The hydrogel possesses adhesive and self-healing properties, offering a microenvironment with excellent cell compatibility for exogenous BMSCs. In vivo studies showed that this hydrogel significantly accelerated the healing of acute full-thickness skin wounds, resulting in the formation of appendages such as hair follicles and minimal scarring. This study not only presents a novel skin tissue engineering scaffold but also offers a promising clinical strategy for achieving scar-minimized wound healing.

Keywords: Hyaluronic acid; Tissue engineering; Wound healing.