Collaborative Research: Fluid Dynamics Foundations of Cell Printing

0936235/0936238乔/徐结构细胞打印，即打印组织基质中细胞的三维结构，长期以来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，并使许多领域能够取得革命性的突破。尽管人们非常担心，尤其是细胞能否在严酷的印刷过程中幸存下来，但SCP的可行性最近已经得到证明。然而，尽管SCP的研究取得了爆炸性的增长，但这项技术仍处于起步阶段，许多关键问题仍未解决。最重要的是，细胞沉积的分辨率还没有达到，细胞存活率还有待提高。解决这些问题需要对SCP过程有透彻的了解。本项目的目标是研究基于喷墨的SCP工艺的关键步骤，即使用集成的实验和建模方法将细胞液滴打印到薄膜上形成二维细胞图案。将研究这一关键步骤的两个单位操作，即以单个单元为特征的点的打印(单元点)和单元线(单元线)的打印。细胞斑点印刷的研究将集中在阐明细胞液滴撞击液膜的动力学，重点是液滴的扩散和渗透行为以及细胞的应力演变，这决定了细胞沉积的分辨率和细胞的存活率。细胞线打印的研究将集中于描绘顺序打印的细胞负载液滴之间的相互作用，以及这些相互作用如何影响液滴液膜撞击、液滴内细胞的应力，最终影响细胞沉积分辨率和细胞存活率。智能优点：所提出的研究是对基于喷墨的SCP技术中涉及的流体动力学的开创性研究。所获得的见解将为合理设计SCP工艺以实现最佳的细胞沉积分辨率和细胞存活率提供知识基础，从而有助于消除这一新技术发挥其最大潜力的关键障碍。通过描绘SCP过程特有的液滴和细胞动力学，例如，细胞在微秒级极强剪切流中的动力学，本研究还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在细胞印刷和多物理模拟方面具有互补专业知识的私人投资机构之间的协同合作，并得到最先进的实验和计算设施的支持。广泛的影响：该项目将与私人投资机构本土机构的本科生研究生教育密切相关。参与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。将利用各种资源，例如，私人投资机构的少数族裔招聘方案，从代表性不足的群体中招募学生参加这一项目。研究成果将被制作成电影，用于K-12外展活动，并提交给由Efluid.com主办的流体运动/图像画廊。为了帮助将研究传播给普通读者，并帮助他们认识到流体动力学研究在开发有用技术方面的重要性，我们将开发一个名为细胞打印的书呆子一面的网站。该网站将通过使用普通公众容易理解的实验/计算机生成的图像和电影来解释结构细胞打印所涉及的流体动力学。网站将通过正式和非正式渠道向目标受众进行广告宣传。

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.