Authors Lohmann, N. ; Schirmer, L. ; Atallah, P. ; Wandel, E. ; Ferrer, R. A. ; Werner, C. ; Simon, J. C. ; Franz, S. ; Freudenberg, U.
Title Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice
Date 08.03.2018
Number 55466
Abstract Chronic wounds represent a challenge to conventional wound treatments. As a result, novel materials for the targeted treatment are urgently needed. Excessive production of inflammatory chemokines, establishing chemoattractant gradients, can cause chronic inflammation and therefore impair wound healing. Accordingly, capturing such chemokine signals using wound dressing materials may attenuate inflammation and thus may become a powerful treatment option for chronic wounds. <br />In here, a modular hydrogel based on star–shaped polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG) heparin was customized for maximal chemokine sequestration. The engineered hydrogel has been shown to effectively scavenge the pro–inflammatory chemokines MCP–1 (monocyte chemoattractant protein–1), IL–8 (interleukin–8), MIP–1a (macrophage inflammatory protein–1 alpha), and MIP–1ß (macrophage inflammatory protein–1 beta) from wound fluids from patients suffering from chronic venous leg ulcers. Consequently, starPEG–GAG hydrogels considerably reduced the migratory activity of human monocytes and polymorphonuclear neutrophils using inflammatory conditioned medium and decreased the immune cell influx and inflammatory signaling in wound sites in a murine model of full–thickness excisional wounds (C57BL/6 mice). Finally, starPEGGAG hydrogels suppressed wound inflammation and improved granulation tissue formation, vascularization, and wound closure in an in vivo model of delayed wound healing (db/db mice). <br />Further testing of the promising starPEG–GAG materials may pave the way for a potential future application in human patients. Beyond that, the underlying concept is expected to be similarly applicable in the treatment of other disorders associated with pathologically enhanced inflammatory processes.
Publisher Experimental Dermatology
Citation Experimental Dermatology 27 (2018) E18-E19, P0043

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