Effects of Curved Substrates on Human Macrophages

Abstract

Bone regeneration and osseointegration are important factors for orthopedic implant success. Osteoimmunomodulation (OIM) has emerged as a design strategy to guide macrophage polarization through biomaterial surface properties, promoting the immune conditions that favours osseointegration. While discrete topographic features have been extensively studied, substrate curvature as a continuously variable geometric cue remains underexplored. This thesis investigated whether curvature orientation influences human THP-1-derived macrophage behaviour, using polystyrene substrates with convex (cvPS) and concave (ccPS) unduloid geometries compared to flat controls (fPS).
Although a decrease of M1 macrophages, both M0 and M1 are found viable on all substrates. Curvature orientation influenced spatial distribution: macrophages on ccPS preferentially localised within concave unduloid regions, while on cvPS cells accumulated relatively more in the flat interspaces by day 3. Three morphological categories were identified across all surfaces, with a general temporal shift toward rounded morphologies by day 3 independent of substrate geometry. M0 macrophages on curved substrates showed upregulation of TNFA, CD86 and CD206, while M1 macrophages mainly showed trends toward increased anti-inflammatory gene expression with high inter-experimental variability.
These results provide the first evidence that unduloid surface curvature influences macrophage spatial organisation and gene expression, supporting substrate curvature as a relevant and tunable parameter for osteoimmunomodulatory biomaterial design.