EAGER: Cybermanufacturing: Cloud-based, Rapid, Microscale 3D Bioprinting

精密组织工程是一个新兴领域，它将工程和生命科学的原理应用于生物替代品的开发，以恢复、维持或改善组织功能或整个器官。组织工程的成功依赖于用种子/包被活细胞制造/打印复杂的、功能性的三维结构的能力。当前的打印技术通常非常缓慢，对细胞的打印分辨率有限，并且在完全复制体内环境的能力方面受到限制，无论是在使用的材料，细胞分布还是天然生理的复杂几何形状方面。这些生物打印机通常是单独的实验室/工厂为基础，不能进入更广泛的科学界。这项探索性研究（EAGER）早期概念资助支持基础研究，为基于云的快速3D生物打印平台的开发提供所需的知识，该平台可创建用于新兴精准医学领域的功能组织。通过使用预期的系统，研究团队将能够创建专门的工具，并通过云与生物医学科学界共享关键数据。因此，这项研究的结果将有利于美国的经济和社会。这项研究涉及多个学科，包括制造、生物材料科学、云计算和精准医学。多学科方法将有助于扩大代表性不足的群体在研究中的参与，并对工程教育产生积极影响。该项目提出了一种简单快速的制造方法，将细胞封装在复杂的3D几何形状中，使用数字印刷和自然衍生的明胶基水凝胶相结合。通过提供无扫描打印，制造的结构将不会表现出由传统的逐点和逐层制造方法引起的平面伪影，这些方法涉及线性阶段到新位置的离散运动。这样的生物打印平台可以比传统的生物绘图仪创造更好的组织结构的机械完整性。在制造过程中使用的大分子溶液可以很容易地改变，以加入各种生物活性分子，如生长因子、药物或遗传线索以及多种细胞类型。这项工作填补了该领域的巨大知识空白，开发了一种可扩展的技术，用于快速制造精密医学的复杂3D细胞负载支架。基于云的软件架构将提供模块化、可扩展、远程访问和用户友好的“web应用程序”，以增强生物打印平台跨多个用户的协作潜力。研究团队将通过实验和模拟来了解光与聚合物链相互作用的机理，并建立3d打印组织支架的工艺参数与力学性能之间的关系。

Precision tissue engineering is an emerging field that applies the principles of engineering and life sciences to the development of biological substitutes that restore, maintain or improve tissue function or a whole organ. The success of tissue engineering relies on the ability to manufacture/print complex, functional three-dimensional structures with seeded/encapsulated live cells. Current printing techniques are typically very slow, have limited printing resolution for cells, and are limited in their ability to fully replicate the in vivo environment, either in terms of the material used, the distribution of cells, or the complex geometries of the native physiology. These bioprinters are usually individual lab/fab based, not accessible to the broader scientific communities. This EArly-concept Grant for Exploratory Research (EAGER) award supports fundamental research to provide needed knowledge for the development of a cloud-based, rapid, 3D bioprinting platform that creates functional tissues with application to the emerging field of precision medicine. By using the anticipated system, a research team will be able to create specialized tools and share critical data with the biomedical science community through the cloud. Therefore, results from this research will benefit the U.S. economy and society. This research involves several disciplines including manufacturing, biomaterials science, cloud computing, and precision medicine. The multi-disciplinary approach will help broaden participation of underrepresented groups in research and positively impact engineering education.This project presents a simple and rapid fabrication approach for encapsulating cells within complex 3D geometries using a combination of digital printing and a naturally-derived gelatin-based hydrogel. By providing scanless printing, the fabricated structures will not exhibit the planar artifacts induced by traditional drop-by-drop and layer-by-layer fabrication approaches that involve discrete movement of the linear stage to a new position. Such a bioprinting platform can create much better mechanical integrity of the tissue construct than a traditional bioplotter. The macromer solution used during fabrication can easily be changed to incorporate a variety of bioactive molecules, such as growth factors, drugs, or genetic cues along with multiple cell types. This work fills a large knowledge gap in the field for developing a scalable technique for rapidly fabricating complex 3D cell-laden scaffolds for precision medicine. The cloud-based software architecture will provide a modular, extensible, remotely accessible, and user-friendly "web app" to enhance the collaborative potential of the bioprinting platform across multiple users. The research team will perform experiments and simulation to understand the mechanism of light interactions with polymer chains, and establish relationships between process parameters and mechanical properties of the 3D-printed tissue scaffolds.