Vascularization of Microfluidic Hydrogels

Current methods for engineering vascularized tissues rely primarily on the self-organization of vascular cells (endothelial cells, pericytes, and smooth muscle cells) or their progenitors in a scaffold and/or on the recruitment of new vessels via release of angiogenic factors [1,2]. While these approaches certainly accelerate the process of graft vascularization, they still require several days to achieve perfusion of the graft. It is difficult to see how thick, densely cellularized grafts (e.g., a myocardial patch) could survive the stagnant transition period that separates in vitro culture from in vivo perfusion. In clinical tissue transplantation, grafted tissues are almost always (re)perfused upon completion of the surgical procedure. For instance, successful transfer of a “free flap” between distant regions of the human body requires microvascular anastomoses between the small vessels that feed the tissue and those that reside in the recipient bed [3]. Insetting the graft without establishing such anastomoses usually leads to necrosis of the graft (with the exception of thin tissues such as epidermal grafts). These issues have prompted us and others to investigate how to create tissues that can be immediately perfused. Our approach is to form scaffolds that contain microfluidic networks that serve both as channels for perfusion and as templates for vascular growth [4 6]. We emphasize that such an approach differs from the “prevascularization” that often results in organization of vascular cells into short segments that have not been shown to sustain flow across the entire scaffold [7,8]. This chapter describes methods to form, vascularize, and optimize microfluidic scaffolds for perfusion of engineered tissues, and proposes a computational algorithm to simplify the design of microfluidic scaffolds for this application.