Hak-Joon Sung
Assistant Professor of Biomedical Engineering, Assistant Professor of Medicine-Cardiovascular Medicine
Last active: 2/12/2015

Elucidation of adhesion-dependent spontaneous apoptosis in macrophages using phase separated PEG/polyurethane films.

Zachman AL, Page JM, Prabhakar G, Guelcher SA, Sung HJ
Acta Biomater. 2013 9 (2): 4964-75

PMID: 23128157 · PMCID: PMC3606556 · DOI:10.1016/j.actbio.2012.10.038

Circulating monocytes undergo spontaneous apoptosis when there is no activation stimulus, which is critical to population control for proper host response to implants. As activation and apoptosis of monocytes/macrophages are regulated by cell-cell and cell-matrix interactions, their regulatory mechanism was investigated in this study using polyethylene glycol (PEG)-containing polyurethane films in which PEG-rich and polyester-rich domains were phase separated. Human blood monocyte-derived macrophages (HBMs) preferentially adhered to PEG domains (cell-matrix interaction) due to the low molecular weight (600 g mol⁻¹), resulting in increased HBM density (cell-cell interaction). As both cell-cell and cell-matrix interactions were promoted, HBM apoptosis increased, while their activation as measured by phagocytosis, intracellular reactive oxygen species (ROS) level and matrix metalloproteinase-9 production decreased compared to PEG-free films. When cell seeding density and cell-adhesive gelatin coating on silicone films were controlled, a cooperative role of cell-matrix (adhesion) and cell-cell (density) interactions in inducing HBM apoptosis was observed. Expression of the macrophage adhesion molecule CD11b caused apoptosis in this context, which was mediated by tissue necrosis factor-α signaling but down-regulated by the ROS inhibitor diphenylene iodonium and the anti-inflammatory peptide Ac-SDKP, suggesting a new concept for the design of biomaterials that allows for cell adhesion without excessive inflammatory activation.

Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

MeSH Terms (20)

Adsorption Apoptosis Cell Adhesion Cell Communication Cell Count Cell Proliferation Collagen Cytokines Enzyme Activation Extracellular Matrix Humans Human Umbilical Vein Endothelial Cells Inflammation Intracellular Space Macrophages Matrix Metalloproteinase 9 Polyethylene Glycols Polyurethanes Reactive Oxygen Species Spectroscopy, Fourier Transform Infrared

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