Research ArticleWound Healing

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

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Science Translational Medicine  19 Apr 2017:
Vol. 9, Issue 386, eaai9044
DOI: 10.1126/scitranslmed.aai9044

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Capturing chemokines in chronic wounds

Chronic, poor healing wounds are characterized by the lack of resolution of initial proinflammatory signaling present during acute injury. Lohmann et al. designed a synthetic hydrogel wound dressing based on heparin, a glycosaminoglycan that can bind and sequester chemokines. The hydrogel mopped up inflammatory chemokines such as MCP-1 and IL-8 from fluid from patients’ chronic venous leg ulcers in vitro and inhibited neutrophil and monocyte migration. Applying the hydrogel to skin wounds in diabetic mice improved wound healing and vascularization and reduced inflammation more effectively than the FDA-approved hydrogel Promogran. Capturing chemokines may be an effective strategy to promote tissue regeneration in chronic wounds.

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.

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