Project 463386

Vascularization is an indispensable requirement of fabricating large solid tissues and organs. The vascular networks in the human body differ among the organs and tissues. In a typical network, the blood flows into the tissues through arteries which sub-divide into arterioles. The arterioles sub-divide to form capillaries that participate in the exchange of nutrients and waste through diffusive mass transport. Further, the capillaries merge to form venules which, in turn, merge to form the veins for outflow of the blood from the tissue. A few studies have attempted to fabricate perfusable scaffolds using sacrificial materials which formed simple hollow channels as the vasculature or geometrically simple closed networks which resulted in blood flow shunting and required more complexity in their architecture. Therefore, a more complex and biomimetic vasculature capable of nutrient transport to the entire bioprinted organ is needed. Since porous hydrogels are used for fabricating these vascular tissues/organs the diffusive mass transport from the vasculature walls occurs until the endothelial lumens are formed. The surrounding cells rely on this diffusive transport until the capillaries are formed by angiogenesis. Hence, the fabricated vasculature should be simplified to meet the bioprinting capabilities and sufficiently complex to provide nutrient transport to the entire scaffold during the tissue/organ maturation period. We propose to develop a numerical model of designing the vasculature by utilizing the tissue/organ anatomy. Starting with processing the patient's medical images, organ structure, tissue-specific cues, and key vasculature tethers will be determined for guiding the vasculature. The generated 3D networks will be used to model nutrient transport and consumption in the organ and optimize the vasculature in an iterative manner. The resulting personalized networks can ensure uniform cell growth and maturation of bioprinted tissues for faster regeneration.