Macrophages Influence Vessel Formation in 3D Bioactive Hydrogels

Abstract

Macrophages may play a beneficial role in blood vessel development. To study the role of macrophages in vessel development for regenerative medicine, a bioactive poly(ethylene glycol)‐based hydrogel scaffold that is modified for integrin‐mediated cell adhesion and biodegradation by matrix‐metalloproteinases 2 and 9 is utilized. This scaffold serves as a tunable cell microenvironment and supports the formation of microvascular networks. When encapsulated with endothelial cells, macrophages enhance vessel tubule volume within the hydrogel by nearly twofold compared to endothelial cells alone in hydrogels. Additionally, macrophages in the hydrogel alter their morphology in an endothelial cell‐dependent manner. Macrophages alone maintain high circularity with only 1% of the population demonstrating circularity ≤0.5 (indicating cell spreading), but when co‐encapsulated with endothelial cells, 46% of macrophages have a circularity ≤0.5. Macrophages 0–5 µm away from an endothelial cell have a circularity of 0.48 ± 0.22 whereas macrophages >20 µm away have a circularity of 0.83 ± 0.07. Two types of macrophage–endothelial cell interactions are seen: macrophages behaving as pericyte‐like cells and macrophages bridging between endothelial cells. Macrophages may be a novel cell target for regenerative medicine efforts where vasculature is often vital to success.