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General Cross-Cutting - New Organ Alliance

General Cross-Cutting
Vascularization Challenges

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General cross-cutting
sub-challenges

  • Improve Understanding of Angiogenesis: more detailed understanding of the process of angiogenesis is needed for all research strategies. Creating strong, cohesive blood vessels during tissue development is difficult. Understanding blood vessel structures to allow proper nutrient diffusion without edema is critical.
  • Improve Understanding of Stem Cell Differentiation Protocols and Markers: more detail is needed to adequately understand the signals received by stem cells that produce various daughter cells. We need to better understand how to create each cell type from stem cells with the appropriate biomarkers and differentiation protocols. Additionally, there are differences in these properties between tissues that need to be better understood.
  • Define the Topology and 3d Structure of Microvasculature for Each Tissue: not enough is known about the topology of microvasculature for tissues, especially as it relates to vessel properties and network function. Improved understanding of the placement and density of capillaries throughout the tissue will aid in tissue engineering of all organs. Additional knowledge on whole-organ 3D structures is required. Creation of a comprehensive cell atlas would be beneficial.
  • Improve Understanding and Control of Cellular Microfluidics: how do cells in each type of tissue handle fluid exchange including: waste, catabolism, xenobiotic excretion. How much is required, and how does vasculature provide for these requirements? How do gradients between cells impact microfluidic exchange?
  • Identify Reliable and Available Growth Factors: improved understanding of how cells are signaled to develop into specific tissues with the appropriate cell types is needed. When and how much are these growth factors delivered to each cell type to signal appropriate growth and differentiation?
  • Improve Understanding of the Arterial-Venous gap: additional knowledge on the fluid exchange between arteries and veins is required. What is appropriate structure and development for connection (or separation) between arteries and veins in tissues. Specifically, when is venous return necessary for an engineered tissue?
  • Understand How to Integrate Engineered Tissue Vasculature with Host: the connection of large vessels is a major engineering problem that has not yet been achieved. Techniques for integration of engineered vasculature are required.
  • Be able to Incorporate Stable Lymph Vessels into thick vascularized tissues: controlling the development and connection between lymph nodes/vessels and vasculature in thick tissues will be critical for complex tissue development.
  • Understand the Developmental Timeline for Vasculature in Each Tissue: as tissues and organs grow, we need to understand what happens when, and specifically how much vasculature is produced when and where.

    • Cardiovascular Sub-Note: myocyte endothelial vasculature development happens rapidly, allowing the nascent heart to begin beating very early driving in turn electrical maturation, further development and increased vasculature. We need to know where vascular cells come from and when they are important. Muscle cells in the heart form first then endothelial cells; vasculature comes relatively late in the development of the heart. We are still in the early stages of understanding signals for this development.

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