Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice

Abstract

Excessive production of inflammatory chemokines can cause chronic inflammation and thus impair cutaneous wound healing. Capturing chemokine signals using wound dressing materials may offer powerful new treatment modalities for chronic wounds. Here, a modular hydrogel based on end-functionalized star-shaped polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG) heparin was customized for maximal chemokine sequestration. The material is shown to effectively scavenge the inflammatory chemokines MCP-1 (monocyte chemoattractant protein-1), IL-8 (interleukin-8), and MIP-1α (macrophage inflammatory protein-1α) and MIP-1β (macrophage inflammatory protein-1β) in wound fluids from patients suffering from chronic venous leg ulcers and to reduce the migratory activity of human monocytes and polymorphonuclear neutrophils. In an in vivo model of delayed wound healing (db/db mice), starPEG-GAG hydrogels outperformed the standard-of-care product Promogran with respect to reduction of inflammation, as well as increased granulation tissue formation, vascularization, and wound closure.