Directional control of angiogenesis to produce a designed multiscale micro-vascular network with bioprinting

Abstract

Department of Biomedical EngineeringThe biomimetic vascular network is a key element in regeneration of viable, functional and scalable artificial tissues. In this study, we developed a multiscale vascular network that can be patterned freely by using bioprinting technology. An endothelialized channel of several hundred micrometer scale was directly printed. The micro-vascular network consisting of tubular structures of several tens of micrometers was generated through the direction control of angiogenic sprouting using the chemotaxis effect. For this purpose, human umbilical vein endothelial cells (HUVEC) and angiogenic factor secreting cells, normal human dermal fibroblasts (NHDF), were co-patterned at 1 to 2 mm intervals using water soluble bio-ink and alginate based bio-ink, respectively. Then, a bridge pattern connecting the two patterned gels was made with fibrin gel. After printing, an endothelialized channel of about 800 ??m was formed by selective removal of water soluble bio-ink. The angiogenic sprouting was induced at about 200 ??m/day along the bridge pattern from the channel. It was also possible to fabricate a multiscale micro-vascular network with diagonal, wave and branch shapes using bridge patterns of various designs. In this study, we investigated the functionality of hepatocytes by co-culturing mouse primary hepatocytes after fabricating a vascular construct with hepatic lobule-shaped pattern to confirm the utility of the constructed process. As a result, we could confirm largely improved albumin and urea secretion. Based on these results, we confirmed that the tissue specific multiscale vascular network could be constructed. This technique should provide a useful tool for the development of functional and scalable vascularized tissues.clos