EAGER: Scanningless 3D Bioprinting of Multiple Biomaterials and Cells for Biomimetic Vascular Network

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Vascularization has been the bottleneck for engineering large-scale or highly metabolic tissues. Without vascular support, cellular viability and function of engineered tissues or organs will be compromised in very short time. Traditional biomanufacturing methods such as nozzle-based and ink-jet based 3D printing are often slow and have limited printing resolution for creating biomimetic vasculature. This EArly-concept Grant for Exploratory Research (EAGER) award supports fundamental research on a new biomanufacturing method that simultaneously offers the speed, the resolution, and the ability to process multiple biomaterials and cells to 3D print biomimetic vascular network. Results from this research will potentially transform the biomanufacturing field for future tissue and organ printing with biomimetic vascular network. Printing organs such as heart and liver will reduce the shortage of donor organs for transplantations and save lives. Additionally, the biomimetic in vitro tissue models could significantly benefit the pharmatheutical industry because they can be used in early drug screening for drug toxicity and efficacy testing.The new biomanufacturing method features ultraviolet light-induced hydrogel formation in a scanningless and continuous fashion for rapid 3D printing of biomimetic vascular network. The first research objective is to understand the effects of material composition and processing parameters on mechanical properties of the hydrogel scaffolds for the 3D printing process. To achieve this objective, glycidal methacrylate-hyaluronic acid and gelatin methacrylate will be synthesized as the hydrogel materials with different methacrylation ratios. Hydrogel scaffolds will be printed by varying material composition (such as molecular weight and concentration of the monomers) and processing parameters (such as ultraviolet light intensity and exposure time). Mechanical properties (such as stiffness and yield strength) of printed hydrogel scaffolds will be measured by a nanoindentor and dynamic mechanical analyzer. The second objective is to understand how scaffold shape and chemistry affect vascular network formation. To achieve this objective, scaffolds of different shapes including single tubes and branched tubes will be printed using different hydrogels (glycidal methacrylate-hyaluronic acid and gelatin methacrylate). Human umbilical vein endothelial cells and mesenchymal stem cells will be encapsulated in the hydrogels to form a vascularized tissue. Vascular network formation such as lumens will be imaged using confocal microscopy.