Bioprinting Vascular Networks in Scaffolds

Abstract

An interconnected vascular network is required to maintain the viability and biological function of a large cell population in growing tissue. In vivo, well-distributed vascular capillaries are seen in different tissues at a distance of every ~100–200 µm. Tissue regeneration with the aid of scaffolds, particularly large and thick scaffolds, requires the incorporation of an interconnected vascular network to facilitate mass transfer of nutrients, signaling molecules, oxygen, growth factors, metabolic waste, etc., between the cells within scaffolds and the culture medium or blood. As such, understanding in vivo blood vessels and their formation is essential to the design and fabrication of functional vascular networks within engineered constructs or scaffolds. As such, vascular anatomy and capillary vessel formation mechanisms in vivo are discussed in the first part of this chapter. To fabricate a vascularized tissue scaffold, direct and indirect approaches based on bioprinting are used to create a capillary-like structure or macro-blood vessels. The direct approach allows the biofabrication of lumen-containing strands within the scaffolds, analogous to native vessels. In this approach, cell/hydrogel mixtures are used as a bioink, with growth factors, proteins, and peptides often added to enhance the biofunctionality of the bioink. In the indirect approach, vascular networks are generated within the scaffold by removing sacrificial strands that are created by bioprinting or other additive manufacturing techniques. Biopolymer free approaches, such as de-cellularized native tissue, self-assembled tissue filaments or cell aggregates, and cell sheets, have also been considered as appropriate for the formation of macro- or micro-blood vessels. The second part of this chapter introduces these bioprinting-based approaches and others to create vascular networks within tissue scaffolds, along with the merits and limitations associated with each approach discussed.