Determining the cross-talk between smooth muscle cells and macrophages on a cobalt-chromium stent material surface using an in vitro postimplantation coculture model.

Abstract

Smooth muscle cells (SMCs) and macrophages are important cellular components involved in the development of complications following the implantation of cardiovascular devices. This leads to various disorders such as restenosis, chronic inflammation, and may ultimately result in device failure. In this study, we developed a postimplant stent coculture model using different ratios of SMCs and macrophages seeded on to cobalt-chromium alloy. The macrophages had an increased affinity to the coculture surfaces, which resulted in decreased SMC attachment to the alloy surfaces at the initial time point. Once adhered, the macrophages spread freely and displayed advanced stages of inflammation at 48 h when cocultured with SMCs. This resulted in an increased secretion of proinflammatory cytokines (tumor necrosis factor alpha, monocyte chemotactic protein 1, interleukin [IL]-6, and IL-8) by 48 h in the coculture samples with the greatest increase observed with the high number of macrophages. Therefore, the increased levels of proinflammatory cytokines promoted the growth of SMCs in coculture to a greater extent than when the SMCs were culture alone. Thus, this study demonstrated the constant cross-talk between SMCs and macrophages occurring on the postimplant stent surface. Similar coculture models can be used to test the biocompatibility of drugs and biomaterials at possible postimplantation scenarios. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 673-685, 2018.