Uniform pore morphology of bijel-templated materials reduces cell circularity and inflammatory expression of macrophages

The design of implantable biomaterials often aims to guide local cell behavior to control immune response. Non-chemical routes exploit the effect of mechanical properties and structure morphology on cell behavior. A class of substrates known as bicontinuous interfacially jammed emulsion gel (bijel)-templated materials (BTMs) exhibit characteristically uniform pore size and surface curvature. Existing research on these materials in vivo demonstrates their ability to modulate the inflammatory response in the anti-inflammatory direction. We investigate a subset of the contributing components to that effect by examining the behavior and phenotype of macrophages within BTMs in vitro. The comparative substrate, the particle-templated material (PTM), has an equivalent chemical composition, but has variable pore size and surface curvature. Macrophages within these two materials take on notably different cell shapes and phenotypes. Macrophages interacting with the BTM exhibit less circular cell shapes and a lower state of inflammation. This effect is significant enough to induce lower pro-fibrotic activation in fibroblasts, without direct BTM-fibroblast contact. These results suggest that microscale curvature and pore size have a direct effect on macrophages, and that this effect can cause phenotypic changes in other cells. Findings reaffirm the significance of targeting macrophages in biomaterials design and support further investigation of the immune signaling cascade that occurs within BTMs. Our contributions to the fundamental knowledge of cell behaviors in these porous materials provide new insights applicable to advancing biomaterials design.