Collaborative Research: Fluid Dynamics Foundations of Cell Printing

0936235/0936238 Qiao/Xu结构细胞打印（SCP），或打印组织基质中细胞的三维结构，一直是一个令人着迷的想法。利用基于液滴的打印技术的微米分辨率，SCP有望实现与单个细胞大小相当的细胞沉积分辨率。在体外实现这样的分辨率将解决组织工程中最根本的挑战之一，并在许多领域实现革命性的突破。尽管存在重大问题，特别是细胞是否能在苛刻的打印过程中存活，但SCP的可行性最近已经得到了证明。然而，尽管SCP研究的爆炸性增长，这种技术仍处于起步阶段，许多关键问题仍未解决。最重要的是，设想的细胞沉积分辨率尚未实现，细胞活力需要提高。要解决这些问题，就必须彻底了解SCP进程。 本项目的目的是研究基于喷墨的SCP工艺中的关键步骤，即，使用集成的实验和建模方法，将载有细胞的液滴打印到薄液膜上以形成二维细胞图案。将研究这一关键步骤的两个单元操作，即，具有单个细胞的点（细胞点）的印刷和细胞线（细胞线）的印刷。细胞点打印的研究将集中于阐明载有细胞的液滴冲击液膜的动力学，重点是液滴的扩散和渗透行为以及细胞的应力演变，这决定了细胞沉积分辨率和细胞活力。细胞系打印的研究将集中在描绘之间的相互作用的顺序打印细胞装载液滴和这些相互作用如何影响液滴液膜的影响，液滴内的细胞的应力，并最终细胞沉积分辨率和细胞活力。智力优点：拟议的研究是一个先驱研究的流体动力学涉及基于喷墨的SCP技术。这里获得的见解将为SCP过程的合理设计提供知识基础，以实现最佳的细胞沉积分辨率和细胞活力，从而有助于消除这种新技术的关键障碍，以充分发挥其潜力。通过描绘SCP过程特有的液滴和细胞动力学，例如，细胞在微秒量级的极强剪切流中的动力学研究，也将丰富液滴和细胞动力学的流体动力学理论。拟议的研究将受益于两个PI之间的协同合作，在细胞打印和多物理学模拟方面具有互补的专业知识，并得到最先进的实验和计算设施的支持。更广泛的影响：该项目将与PI所在机构的本科研究生教育密切相关。参加这个跨学科项目的学生将接触到不同的领域，如流体动力学，细胞力学和生物工程。每年将有五名本科生参与这项研究。各种资源，例如，将利用公共教育学院的少数族裔招生方案，从代表性不足的群体中招收学生参加这一项目。研究结果将被制作成电影，用于K-12外展活动，并提交给Efluid.com主办的流体运动/图像画廊。为了帮助传播研究，以奠定观众，并帮助他们欣赏流体动力学研究在开发有用的技术的重要性，我们将开发一个名为细胞打印的书呆子的一面网站。该网站将通过使用实验/计算机生成的图像和电影来解释结构细胞打印中涉及的流体动力学，这些图像和电影易于公众理解。将通过正式和非正式渠道向目标受众宣传该网站。

0936235/0936238 Qiao/Xu Structural cell printing (SCP), or printing three dimensional structures of cells held in a tissue matrix, has long been a fascinating idea. Drawing on the micrometer resolution of droplet based printing techniques, SCP holds the promise of achieving cell deposition resolution comparable to the size of a single cell. Achieving such a resolution in vitro will resolve one of the most fundamental challenges in tissue engineering and enable revolutionary breakthroughs in numerous areas. Despite significant concerns, in particular whether cells can survive the harsh printing process, the feasibility of SCP has been demonstrated recently. However, despite the explosive growth of research in SCP, such a technique is still in its infancy and many critical issues remain unresolved. Most importantly, the envisioned cell deposition resolution has yet to be achieved and the cell viability needs to be improved. Addressing these issues necessitates a thorough understanding of the SCP process. The objective of this project is to investigate a key step in the ink jet based SCP process, i.e., printing cell laden droplets onto a thin liquid film to form two dimensional cell patterns, using an integrated experimental and modeling approach. Two unit operations of this critical step will be studied, namely, the printing of a dot featuring a single cell (cell dot) and the printing of a line of cells (cell line). The study of cell dot printing will focus on elucidating the dynamics of a cell laden droplet impacting a liquid film with an emphasis on the spreading and penetration behavior of the droplet and the stress evolution of the cell, which govern the cell deposition resolution and cell viability. The study of cell line printing will focus on delineating the interactions between sequentially printed cell-laden droplets and how these interactions affect the droplet liquid film impact, the stress of cells inside the droplets, and ultimately the cell deposition resolution and cell viability.Intellectual Merit: The proposed research is a pioneer study of the fluid dynamics involved in ink jet based SCP techniques. The insights gained here will provide a knowledge base for the rational design of SCP process to achieve optimal cell deposition resolution and cell viability, and thus will help remove critical barriers for this new technique to reach its fullest potential. By delineating the droplet and cell dynamics unique to the SCP process, e.g., the dynamics of cells in exceedingly strong shear flows at microsecond time scale, this research will also enrich the fluid dynamics theories of droplet and cell dynamics. The proposed research will benefit from the synergistic collaboration between two PIs with complementary expertise in cell printing and mutliphysics simulations, and is supported by state-of-the-art experimental and computing facilities.Broader Impacts: The project will be tied closely to the undergraduate graduate education at the PIs home institutions. Students participating in this interdisciplinary project will be exposed to diverse fields such as fluid dynamics, cell mechanics and bioengineering. Five undergraduate students will be involved in the research each year. Various resources, e.g., the minority recruitment programs at the PIs institutions, will be utilized to recruit students from underrepresented groups to participate in this project. Research results will be developed into movies for use in K-12 outreach activities and for submission to the gallery of fluid motion/image hosted by Efluid.com. To help disseminate research to lay audiences and to help them appreciate the significance of fluid dynamics research in developing useful technologies, we will develop a website named The Nerdy Side of Cell Printing. This website will explain the fluid dynamics involved in structural cell printing by using experiment/computer generated images and movies that are easily understandable to the general public. The website will be advertised to the target audience via formal and informal channels.