Engineered molecular delivery for control and enhancement of transplanted endothelial cell fate in tissue engineering

A successful engineered tissue construct must acquire a functional microvascular network that rapidly connects to the host circulation. Suspended endothelial cells (EC) within a construct will spontaneously organize into a microvascular system, but maturation depends on recruitment of host mural cells and is slow and limited. We have integrated protein delivery with transplantation of EC to create multifunctional hydrogels for use in tissue engineering. These gels consist of a protein matrix that facilitates formation of nascent endothelium and alginate microparticles capable of sustained release of multiple protein therapeutics. We have shown that delivery of vascular endothelial growth factor (VEGF) accelerates the development of graft perfusion. In this study, we examine the effects of concurrent delivery of VEGF and monocyte chemoattractant protein-1 (MCP-1). We show MCP-1 release can be achieved at physiologically relevant levels for 48-72 hours, enhancing recruitment of host monocytes, a cell population that may foster angiogenesis and vascular remodeling (arteriogeneisis). Furthermore, our results indicate combining VEGF with MCP-1 delivery facilitates improved engraftment of transplanted EC in a mouse model. These data herald the utility of combined delivery of arteriogenic (MCP-1) and angiogenic (VEGF) growth factors from EC-containing hydrogels as a promising biomaterial strategy for advanced tissue engineering.