The Influence of Sulfation Degree of Glycosaminoglycan-Functionalized 3D Collagen I Networks on Cytokine Profiles of In Vitro Macrophage–Fibroblast Cocultures

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Franziska Ullm - , Universität Leipzig (Autor:in)
  • Alexander Renner - , Universität Leipzig (Autor:in)
  • Uwe Freudenberg - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Carsten Werner - , Professur für Biofunktionale Polymermaterialien (gB/IPF), Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Tilo Pompe - , Universität Leipzig, Leibniz-Institut für Polymerforschung Dresden (Autor:in)

Abstract

Cell–cell interactions between fibroblasts and immune cells, like macrophages, are influenced by interaction with the surrounding extracellular matrix during wound healing. In vitro hydrogel models that mimic and modulate these interactions, especially of soluble mediators like cytokines, may allow for a more detailed investigation of immunomodulatory processes. In the present study, a biomimetic extracellular matrix model based on fibrillar 3D collagen I networks with a functionalization with heparin or 6-ON-desulfated heparin, as mimics of naturally occurring heparan sulfate, was developed to modulate cytokine binding effects with the hydrogel matrix. The constitution and microstructure of the collagen I network were found to be stable throughout the 7-day culture period. A coculture study of primary human fibroblasts/myofibroblasts and M-CSF-stimulated macrophages was used to show its applicability to simulate processes of progressed wound healing. The quantification of secreted cytokines (IL-8, IL-10, IL-6, FGF-2) in the cell culture supernatant demonstrated the differential impact of glycosaminoglycan functionalization of the collagen I network. Most prominently, IL-6 and FGF-2 were shown to be regulated by the cell culture condition and network constitution, indicating changes in paracrine and autocrine cell–cell communication of the fibroblast–macrophage coculture. From this perspective, we consider our newly established in vitro hydrogel model suitable for mechanistic coculture analyses of primary human cells to unravel the role of extracellular matrix factors in key events of tissue regeneration and beyond.

Details

OriginalspracheEnglisch
Aufsatznummer450
FachzeitschriftGels
Jahrgang10
Ausgabenummer7
PublikationsstatusVeröffentlicht - Juli 2024
Peer-Review-StatusJa

Externe IDs

ORCID /0000-0003-0189-3448/work/166763380

Schlagworte

Schlagwörter

  • 3D hydrogels, coculture, collagen I networks, glycosaminoglycans, macrophages, wound healing