Engineering the multiscale complexity of vascular networks

The survival of vertebrate organisms depends on highly regulated delivery of oxygen and nutrients through vascular networks that pervade nearly all tissues in the body. Dysregulation of these vascular networks is implicated in many common human diseases such as hypertension, coronary artery disease, diabetes and cancer. Therefore, engineers have sought to create vascular networks within engineered tissues for applications such as regenerative therapies, human disease modelling and pharmacological testing. Yet engineering vascular networks has historically remained difficult, owing to both incomplete understanding of vascular structure and technical limitations for vascular fabrication. This Review highlights the materials advances that have enabled transformative progress in vascular engineering by ushering in new tools for both visualizing and building vasculature. New methods such as bioprinting, organoids and microfluidic systems are discussed, which have enabled the fabrication of 3D vascular topologies at a cellular scale with lumen perfusion. These approaches to vascular engineering are categorized into technology-driven and nature-driven approaches. Finally, the remaining knowledge gaps, emerging frontiers and opportunities for this field are highlighted, including the steps required to replicate the multiscale complexity of vascular networks found in nature.