Supplement-free induction of macrophage polarization solely through the topography of materials is an auspicious strategy but has so far significantly lacked behind the efficiency and intensity of media-supplementation based proto-cols. We investigated Melt-Electrowriting (MEW) for the fabrication of fibrous 3D scaffolds made from poly(ε-caprolactone) (PCL) and advanced the precisely defined inter-fiber spacing from 100 µm down to 40 µm for a variety of pore geometries (rectangular, triangular and round) with the aim to identify structural design criteria for the fabrication of scaffolds with strong topographic immunomodulation for human monocyte-derived macrophages. These scaffolds did facilitate primary human macrophage differentiation towards the M2 type, which was most pronounced for box-shaped pores with 40 µm inter-fiber spacing, but not with the desired efficiency .
We then found that human monocyte-derived macrophages show a strong M2a like pro-healing polarization when cultured on type I rat-tail collagen fibers but not on collagen I films. Therefore, we hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical biomimetic similarity to native collagen I fibers, would induce a localized macrophage polarization. Through integration of flow directed polymer phase separation into MEW we developed Melt-Electrofibrillation, a process that yields nano-fiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical grade PCL. These biomimetic fibrillar structures indeed induce a pronounced elongation of human monocyte-derived macrophages and unprecedentedly triggered their M2-like polarization similar in efficacy as IL-4 cytokine treatment .
- T. Tylek et al: Precisely De-fined Fiber Scaffolds with 40 µm Porosity Induce Elongation Driven M2-like Polarization of Human Macrophages. Biofabrication, 2020, 12, 025007.
- M. Ryma et al: Translation of Collagen Ultrastructure to Biomaterial Fabrication for Material-Independent but Highly Efficient Topographic Immunomodulation. Advanced Materials 2021, 33(33), 2101228.