In vitro model to study the biomaterial-dependent reaction of macrophages in an inflammatory environment

Background Macrophages play an important role in the reaction to biomaterials, which sometimes have to be used in a surgical field at risk of contamination. The macrophage phenotype in reaction to biomaterials in an inflammatory environment was evaluated in both an in vivo and in vitro setting. Methods In the in vivo setting, polypropylene (PP) biomaterial was implanted for 28 days in the contaminated abdominal wall of rats, and upon removal analysed by routine histology as well as immunohistochemistry for CD68 (marker for macrophages), inducible nitric oxide synthase (iNOS - a marker for proinflammatory M1 macrophages) and CD206 (marker for anti-inflammatory M2 macrophages). For the in vitro model, human peripheral blood monocytes were cultured for 3 days on biomaterials made from PP, collagen (COL), polyethylene terephthalate (PET) and PET coated with collagen (PET+COL). These experiments were performed both with and without lipopolysaccharide and interferon γ stimulation. Secretion of both M1- and M2-related proteins was measured, and a relative M1/M2 index was calculated. Results In vivo, iNOS- and CD206-positive cells were found around the fibres of the implanted PP biomaterial. In vitro, macrophages on both PP and COL biomaterial had a relatively low M1/M2 index. Macrophages on the PET biomaterial had a high M1/M2 index, with the highest increase of M1 cytokines in an inflammatory environment. Macrophages on the PET+COL biomaterial also had a high M1/M2 index. Conclusion Macrophages in an inflammatory environment in vitro still react in a biomaterial-dependent manner. This model can help to select biomaterials that are tolerated best in a surgical environment at risk of contamination. Surgical relevance Biomaterials in an environment at risk of contamination are often not tolerated owing to a high risk of postoperative infection, which may ultimately lead to removal of the biomaterial. An in vitro model with primary human macrophages was used to provide insight into the acute reaction of macrophages to a biomaterial in an inflammatory environment simulated with lipopolysaccharide and interferon γ. The reaction of macrophages in such an inflammatory environment was still biomaterial-dependent. This in vitro model can be used to study the reaction of macrophages to different biomaterials in an inflammatory environment in more detail, and thereby help to select biomaterials that are tolerated best in a surgical environment at risk of contamination. Macrophages react mesh dependently

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