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Authors
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Lohmann, N. ; Schirmer, L. ; Wandel, E. ; Atallah, P. ; Forstreuter, I. ; Ferrer, R. A. ; Freudenberg, U. ; Werner, C. ; Simon, J. C. ; Franz, S.
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Title
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Immunomodulatory potential of starPEG heparin hydrogels on wound healing associated chemokines
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Date
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10.03.2016
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Number
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49861
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Abstract
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Incidences of non-healing wounds are constantly rising and signi·cantly contribute to morbidity and mortality worldwide. Non-healing wounds do not progress the phases of normal wound repair but are stuck in a chronic in·ammatory response. The wound healing process is governed by a wide range of in·ammatory and regenerative signaling molecules. In non-healing wounds the balance of these signals is shifted towards an excess of in·ammatory cytokines leading to continuing in·ltration of immune cells which release more in·ammatory cytokines and promote tissue breakdown. Resolution of this unrestrained in·ammation loop represents an unmet challenge in the treatment of non-healing wounds. Here, we suggest biohybrid starshaped polyethylene glycol (starPEG) heparin hydrogels as sequestration matrix which binds in·ammatory cytokines overproduced in chronic wounds and thus help to restore a healthy wound environment.<br /><br />To determine the hydrogels’ sequestration pro·les for in·ammatory cytokines binding assays with recombinant mediators and supernatants (SN) from activated dermal ·broblast (dFb) or in·ammatory M1 macrophages were performed. In all conditions abundant binding of the chemotactic factors MCP-1 and IL-8 was observed whereas the cytokines IL-1b, TNF and IL-6 were not targeted by the hydrogels. The impact of MCP-1 and IL-8 sequestration on their function as chemoattractant was investigated in a transmigration assay with primary human monocytes and polymorphonuclear cells (PMN). SN derived from activated dFb and r.h. chemokines after incubation with the hydrogels were used as chemotactic stimuli. Indeed, depletion of MCP-1 and IL-8 by the hydrogels decreased migration of monocytes and neutrophils, demonstrating the functional neutralization of these mediators by the hydrogels. Applying these hydrogels in a complex in vivo situation using a wound healing model of full thickness excisional wounds in mice con·rmed their abundant sequestration activity. Chemokines from the wound environment could be detected in the hydrogel networks. In·ltration of monocytes and PMN was quanti·ed in digested wound biopsies by ·ow cytometry. Strikingly, in·ux of neutrophils and monocytes/macrophages were signi·cantly decreased in wounds after application of the hydrogels for 5 days. No haemorrhagic effects were observed. In conclusion, starPEG heparin hydrogels could be of value as immunomodulating wound dressing supporting in·ammatory resolution through the sequestration and neutralization of chemokines and consequential reduction of immune cell in·ltration.<br /><br />Abstract P045 from 43nd Annual Meeting of the Arbeitsgemeinschaft Dermatologische Forschung e.V. (ADF)
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Publisher
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Experimental Dermatology
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Wikidata
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Citation
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Experimental Dermatology 25 (2016) E8
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DOI
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https://doi.org/10.1111/exd.12952
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Tags
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