Three-dimensional nanofibrous polystyrene scaffolds modify macrophage phenotypes and activate macrophage angiogenic potential.

3D scaffolds represent an attractive substrate for studying macrophage activation and modification since they mimic extracellular matrix (ECM). However, macrophage response to such materials, particularly with respect to angiogenic potential is still poorly recognized. Therefore, we investigated the effect of 3D nanofibrous polystyrene scaffolds (NPSs) versus tissue culture polystyrene (TCPS) on THP-1-derived macrophages in various environmental conditions, for example, standard (m0), pro-inflammatory (m1), or anti-inflammatory (m2) with respect to pro-angiogenic potential. There were no differences in the expression of TNF-α and IL-10 mRNAs and respective proteins in cells cultured on NPSs compared with flat polystyrene (TCPS), however, NPSs induced an increased VEGF production by macrophages cultured in m0 and m1 media. Cells cultured in m1, and m2 conditions secreted elevated amounts of TNF-α and IL-10, respectively, irrespective of substrate surface geometry. Each macrophage population contains large, medium, and small cells. Moreover, there were significant differences in the proportion of large to small macrophages depending on the medium composition, that is, in m0, m1, and m2 media these proportions were 1:4, 1:3, and 1:10, respectively. The ultrastructure and the immunoexpression of TNF-α and IL-10 were analyzed under a confocal microscope. The results demonstrated differences in cell ultrastructure and suggested that the larger cells were pro-inflammatory macrophages, while the smaller cells were anti-inflammatory macrophages. In conclusion, NPSs activate macrophage pro-angiogenic potential. In addition, an increase in the proportion of pro-inflammatory macrophages relative to anti-inflammatory ones in a given population favors this potential.