Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation.

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jennifer Kajahn - , Leipzig University (Author)
  • Sandra Franz - (Author)
  • Erik Rueckert - (Author)
  • Inka Forstreuter - (Author)
  • Vera Hintze - , Chair of Biomaterials, Max Bergmann Center of Biomaterials Dresden (Author)
  • Stephanie Moeller - (Author)
  • Jan C. Simon - (Author)

Abstract

Integration of biomaterials into tissues is often disturbed by unopposed activation of macrophages. Immediately after implantation, monocytes are attracted from peripheral blood to the implantation site where they differentiate into macrophages. Inflammatory signals from the sterile tissue injury around the implanted biomaterial mediate the differentiation of monocytes into inflammatory M1 macrophages (M1) via autocrine and paracrine mechanisms. Suppression of sustained M1 differentiation is thought to be crucial to improve implant healing. Here, we explore whether artificial extracellular matrix (aECM) composed of collagen I and hyaluronan (HA) or sulfated HA-derivatives modulate this monocyte differentiation. We mimicked conditions of sterile tissue injury in vitro using a specific cytokine cocktail containing MCP-1, IL-6 and IFNγ, which induced in monocytes a phenotype similar to M1 macrophages (high expression of CD71, HLA-DR but no CD163 and release of high amounts of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12 and TNFα). In the presence of aECMs containing high sulfated HA this monocyte to M1 differentiation was disturbed. Specifically, pro-inflammatory functions were impaired as shown by reduced secretion of IL-1β, IL-8, IL-12 and TNFα. Instead, release of the immunregulatory cytokine IL-10 and expression of CD163, both markers specific for anti-inflammatory M2 macrophages (M2), were induced. We conclude that aECMs composed of collagen I and high sulfated HA possess immunomodulating capacities and skew monocyte to macrophage differentiation induced by pro-inflammatory signals of sterile injury toward M2 polarization suggesting them as an effective coating for biomaterials to improve their integration.

Details

Original languageEnglish
Pages (from-to)226-273
Number of pages48
JournalBiomatter
Volume2
Issue number4
Publication statusPublished - 2012
Peer-reviewedYes

External IDs

PubMed 23507888
ORCID /0000-0002-5611-9903/work/184441862

Keywords

ASJC Scopus subject areas