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

血管化一直是工程化大规模或高代谢组织的瓶颈。如果没有血管的支持，工程化组织或器官的细胞活力和功能将在很短的时间内受到损害。传统的生物制造方法，如基于喷墨和基于喷墨的3D打印通常是缓慢的，并且具有用于创建仿生脉管系统的有限打印分辨率。EARLY概念探索性研究资助（EAGER）奖支持对一种新的生物制造方法的基础研究，该方法同时提供速度，分辨率和处理多种生物材料和细胞的能力，以3D打印仿生血管网络。这项研究的结果将潜在地改变生物制造领域，用于未来具有仿生血管网络的组织和器官打印。打印心脏和肝脏等器官将减少用于移植的捐赠器官短缺，挽救生命。此外，仿生体外组织模型可用于药物毒性和有效性测试的早期药物筛选，因此可为制药行业带来显著效益。这种新的生物制造方法的特点是以无扫描和连续的方式形成紫外光诱导的水凝胶，用于快速3D打印仿生血管网络。第一个研究目标是了解材料组成和工艺参数对3D打印过程中水凝胶支架机械性能的影响。为了实现这一目标，将合成甲基丙烯酸缩水甘油酯-透明质酸和明胶甲基丙烯酸酯作为具有不同甲基丙烯酸酯化比率的水凝胶材料。水凝胶支架将通过改变材料组成（如单体的分子量和浓度）和加工参数（如紫外光强度和曝光时间）来打印。打印的水凝胶支架的机械性能（如刚度和屈服强度）将通过纳米压痕仪和动态力学分析仪测量。第二个目标是了解支架形状和化学成分如何影响血管网络的形成。为了实现这一目标，将使用不同的水凝胶（甲基丙烯酸缩水甘油酯-透明质酸和甲基丙烯酸明胶）打印不同形状的支架，包括单管和支管。将人脐静脉内皮细胞和间充质干细胞包封在水凝胶中以形成血管化组织。将使用共聚焦显微镜对血管网络形成（如管腔）进行成像。

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.