M0 and M2 Macrophages Enhance Vascularization of Tissue Engineering Scaffolds

Abstract

In order to address limitations in the field of tissue engineering, vascularization of scaffolds has been considered. This work focuses on the use of macrophages as a novel cell source to enhance vessel formation within a 3D hydrogel scaffold. The influence macrophages can have on vessel development is generally believed to be dependent on macrophage phenotype. To study the influence of macrophage phenotypes in vessel development, we encapsulated endothelial cells and macrophages into a bioactive poly(ethylene glycol) (PEG)-based hydrogel. Specifically, the hydrogel was modified to be cell-adhesive and sensitive to proteolytic degradation. This hydrogel served as a controlled 3D matrix that can support the spontaneous formation of vascular tubule structures. When co-encapsulated with primary aortic endothelial cells (AECs) in the 3D hydrogel matrix, M2 macrophages enhanced the volume of tubules formed from AECs by nearly threefold when compared to AECs alone. M0 macrophages encapsulated with AECs also enhanced tubule volume by twofold when compared to AECs alone. Conversely, M1 macrophages encapsulated with AECs reduced tubule volume by nearly 90% of the tubule volume observed for AECs alone. We found that M2 and M0 macrophages were more likely to directly interact with endothelial cells within the PEG-based hydrogels than M1 macrophages. This data indicated that M2 macrophages can play a role in enhancing vessel formation. The field of tissue engineering endeavors to create tissues by seeding cells within 3D biodegradable scaffolds. The size of engineered tissue scaffolds is limited due to oxygen and nutrient demands. In order to overcome size limits, blood vessels can be grown in engineered tissues. This work focuses on using macrophages as a cell source to help vessel formation in a scaffold material. Macrophages are present at sites of implantations and are known to influence vessel formation. Macrophages can adopt different characteristics based on environmental cues. We investigate which macrophage characteristics allow macrophages to help vessel formation in engineered tissues.