Precisely defined fiber scaffolds with 40 mu mporosity induce elongation driven M2-like polarization of human macrophages

Macrophages are key players of the innate immune system that can roughly be divided into the proinflammatory M1 type and the anti-inflammatory, pro-healing M2 type. While a transient initial proinflammatory state is helpful, a prolonged inflammation deteriorates a proper healing and subsequent regeneration. One promising strategy to drive macrophage polarization by biomaterials is precise control over biomaterial geometry. For regenerative approaches, it is of particular interest to identify geometrical parameters that direct human macrophage polarization. For this purpose, we advanced melt electrowriting (MEW) towards the fabrication of fibrous scaffolds with box-shaped pores and precise inter-fiber spacing from 100 mu m down to only 40 mu m. These scaffolds facilitate primary human macrophage elongation accompanied by differentiation towards the M2 type, which was most pronounced for the smallest pore size of 40 mu m. These new findings can be important in helping to design new biomaterials with an enhanced positive impact on tissue regeneration.