Scalable Laser Printing of Three-Dimensional Living Tissue Constructs

移植成功率的提高导致了对更多组织和器官的迫切需求。仅在美国，就有大约9.5万人在等待新器官，每天都有一些人在等待移植时死亡。器官打印为解决器官供体短缺问题提供了一个有希望的解决方案。该奖项支持基础研究，以产生能够扩大用于器官打印的基于喷射的无孔激光生物打印技术的知识。这项研究的结果将使激光打印在植入活体组织结构的制造中得到更广泛的应用。此外，该奖项将促进细胞和器官打印生物打印技术的发展，并为细胞行为和药代动力学研究提供三维工程组织。在这种新的激光生物打印技术中，将光学扫描仪集成到激光束传输系统中，以光学引导激光脉冲有效地传输条带的生物墨水，而不是机械地移动条带。本研究的目的是了解激光脉冲诱导的相邻流体射流相互作用对光学扫描仪激光诱导正向转移生物打印过程中的喷射性和可打印性的影响。可喷性将根据射流形成过程中是否能形成两个相邻的明确的射流来评估，可打印性将根据明确的射流能否形成明确的线条来评估。每个激光诱导射流的形成将使用现有的均匀核相爆炸理论进行建模。射流作用下的控制流体连续性和液滴形成的Navier-Stokes方程将采用混合插值有限元法进行空间离散，隐式有限差分法进行时间积分。为了推导出包含控制物理的简化方程组和边界条件，将对控制方程和界面条件进行尺度分析。尺度分析结果将用于验证两个相邻射流作用下不稳定（液滴形成）开始的数值模拟。由此获得的相邻射流相互作用的知识将用于预测打印条件（如光学扫描仪的扫描速度）对喷射性和可打印性的影响，并在细胞管的激光生物打印过程中进一步验证。

The rising success rate of transplants has resulted in a critical need for more tissues and organs. Approximately 95,000 people are on the waiting list for new organs in the US alone, and some die every day waiting for transplants. Organ printing provides a promising solution to the problem of organ donor shortage. This award supports fundamental research to generate knowledge that enables the scale up of a jet-based, orifice-free laser bioprinting technique for organ printing. Results from this research will enable the wider use of laser printing for the fabrication of living tissue constructs for implantation. In addition, this award will promote the development of bioprinting technologies for cell and organ printing and provide three-dimensional engineered tissues for cell behavior and pharmacokinetics studies.In this new laser bioprinting technique, an optical scanner will be incorporated into the laser beam delivery system to optically guide laser pulses to efficiently transfer bioinks of a ribbon instead of mechanically moving the ribbon. The objective of this research is to understand the effects of the interaction of laser pulses-induced adjacent fluid jets on the jettability and printability during optical scanner-enabled laser-induced forward transfer bioprinting. The jettability will be evaluated based on whether two adjacent well-defined jets can be formed during jet formation, and the printability will be assessed based on whether a well-defined line can be formed from well-defined jets. The formation of each laser-induced jet will be modeled using the existing homogenous nucleation-based phase explosion theory. The governing fluid continuity and Navier-Stokes equations for droplet formation under the jet interaction will be solved numerically using a finite element method with mixed interpolation for spatial discretization as well as an implicit finite difference method for time integration. In order to derive a reduced system of equations and boundary conditions containing the governing physics, a scale analysis of the governing equations and interfacial conditions will be performed. The scale analysis results will be used to validate the numerical simulation on the onset of instability (droplet formation) under the effects of two adjacent jets. The resulting knowledge of the interaction of adjacent jets will be used to predict the influences of printing conditions such as the scanning speed of optical scanner on the jettability and printability and further validated during the laser bioprinting of cellular tubes.