Event Abstract

Back to Event

StarPEG-heparin hydrogels as chemokine scavenger to improve aberrant wound healing processes

Nadine Lohmann1, 2, Lucas Schirmer2, 3, Elke Wandel1, 2, Passant Atallah2, 3, Inka Forstreuter1, 2, Uwe Freudenberg2, 3, Carsten Werner2, 3, Jan C. Simon1, 2 and Sandra Franz1, 2
  • 1 Leipzig University, Department of Dermatology, Venerology and Allergology, Germany
  • 2 SFB-TRR67, Collaborative Research CenterMatrixengineering, Germany
  • 3 Center for Regenerative Therapies Dresden, Leibnitz Institute of Polymer Research Dresden, Germany

New ECM based hydrogels are developed to act as immunomodulating wound dressing to bring unrestrained inflammation in chronic wounds under control and thus restore the normal wound healing response[1]. In our approach, we test biohybrid hydrogels composed of poly(ethylene glycol) (starPEG) and heparin derivates varying in their sulfation pattern. Heparin acts as multifunctional cross-linker allowing functionalization of the hydrogels e.g. through biomimetic presentation of growth factors as shown for FGF-2 and VEGF promoting angiogenesis[2]. As heparin is known for its high binding affinity for growth factors, chemokines and cytokines we hypothesize that starPEG-heparin hydrogels are capable to sequester inflammatory mediators from chronic wound sites and by this allow for inflammatory resolution.

Hydrogels were prepared by reacting the carbodiimide/N-hydroxysulfosuccinimide (EDC/s-NHS)-activated carboxylic acid group of heparin with amine-functionalized starPEG. Different heparin derivatives were utilized: standard heparin (SH), N-desulfated heparin (N-DSH) and 6-O/N-desulfated heparin (6ON-DSH). Binding capacities of the hydrogels for inflammatory TNF, IL-1b, IL-6, IL-8 and MCP-1 were examined in an adsorption assay using either recombinant (r.h.) mediators or supernatants (SN) from activated dermal fibroblasts (dFb) or macrophages producing these mediators. Migration of human monocytes (Mon) and PMN was investigated in a transwell chamber migration assay to assess the impact on chemokine bioactivity after hydrogel binding. Hydrogels were applied in a full thickness excisional wound mouse model to test their capability to modulate immune cell influx in vivo. Infiltration of Mon and PMN was analysed in digested wound biopsies on day 5 after wounding by flow cytometry.

Mediator adsorption assays reveal a strong binding of MCP-1 and IL-8 by all starPEG-heparin hydrogels while TNF, IL-1b and IL-6 are only less or not bound. Capacity for chemokine binding of the hydrogels are dependent on the sulfation level of the heparin component (SH>N-DSH≥6ON-DSH). Sequestration of MCP-1 and IL-8 by the hydrogels reduces their bioactivity as shown by significant decreased migration of Mon and PMN towards r.h. chemokines or SN derived from activated dFb after incubation with the hydrogels. Moreover, hydrogels also reduce immune cell influx into wounds. The amount of Mon and PMN is significant reduced in day 5 wounds when starPEG-heparin hydrogels were applied compared to control starPEG-PEG hydrogels.

We conclude that starPEG-heparin hydrogels are capable to sequester chemokines from the wound site and thereby downregulate inflammatory immune cell influx. We suggest that starPEG-heparin hydrogels may have the potential to improve healing of chronic wounds by modulating the inflammatory environment in the wounds. This immunomodulating effect may be additionally enhanced by delivery of mediators (IL-10/IL-4) promoting inflammatory resolution through these hydrogels.

Deutsche Forschungsgemeinschaft (SFB-TR67/A10 and B3)

References:
[1] Franz S. et al., Biomaterials. 32:6692-709, 2011
[2] Zieris A. et al., J. Control Release 156:28-36, 2011

Keywords: Dermatology, Hydrogel, Regenerative Medicine, cytokine

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: New Frontier Oral

Topic: Biomaterials in wound healing

Citation: Lohmann N, Schirmer L, Wandel E, Atallah P, Forstreuter I, Freudenberg U, Werner C, Simon JC and Franz S (2016). StarPEG-heparin hydrogels as chemokine scavenger to improve aberrant wound healing processes. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00956

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 27 Mar 2016; Published Online: 30 Mar 2016.