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Acta Biomater. 2013 Mar;9(3):5621-9. doi: 10.1016/j.actbio.2012.11.016. Epub 2012 Nov 17.

Artificial extracellular matrices composed of collagen I and high-sulfated hyaluronan promote phenotypic and functional modulation of human pro-inflammatory M1 macrophages.

Author information

1
Department of Dermatology, Venerology und Allergology, Leipzig University, 04103 Leipzig, Germany. sandra.franz@medizin.uni-leipzig.de

Abstract

The sequential phases of biomaterial integration and wound healing require different macrophage functions mediated by distinct macrophage subsets. During the initial phase of healing, pro-inflammatory M1 macrophages (MΦ1) are required to clear the wound from microbes and debris; however, their unopposed, persistent activation often leads to disturbed integration of biomaterials and perturbed wound healing. Here we investigated whether pro-inflammatory macrophage functions are affected by immunomodulatory biomaterials based on artificial extracellular matrices (aECM). To address this issue, we tested the capacity of two-dimensional aECM consisting of collagen I and hyaluronan or sulfated derivatives of hyaluronan to affect functions of in vitro polarized human pro-inflammatory MΦ1. The aECM containing high-sulfated hyaluronan substantially decreased inflammatory macrophage functions, including pathogen uptake and release of the pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-12 due to impaired activation of nuclear factor "kappa-light-chain-enhancer" of activated B-cells. Moreover, these macrophages secreted immunregulatory IL-10 and showed reduced activity of the transcription factors signal transducer and activator of transcription 1 and interferon-regulating factor 5, both controlling macrophage polarization to MΦ1 subsets. Our data reveal that the collagen I matrix containing high-sulfated hyaluronan possesses immunomodulating properties and dampens inflammatory macrophage activities by impeding signaling pathways crucial for polarization of pro-inflammatory MΦ1. We therefore suggest this aECM as a promising coating for biomaterials to modulate inflammatory macrophage functions during the healing response and recommend its further testing as a three-dimensional construct and in in vivo models.

PMID:
23168224
DOI:
10.1016/j.actbio.2012.11.016
[Indexed for MEDLINE]

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