Multiscale Modeling and Applications of Three-Dimensional (3D) Laser Bio-printing

生物打印已经成为3D打印最具影响力的应用之一，旨在解决对适合移植的具有长期机械和生物稳定性的生物结构的日益增长的需求，以及改进的药物发现模型。现有的3D生物打印技术使用机电工艺来提供含有活细胞的“墨水”，通常被称为生物墨水。生物油墨对热和机械应力极其敏感，因此现有的生物印刷工艺面临着在印刷过程中保持细胞活力的挑战。在此背景下，我的研究的长期目标是满足对改进的3D生物打印方法的持续需求，该方法(I)与低粘度和高粘度的生物墨水配方兼容，(Ii)能够以高分辨率和高速度产生与生物相关的大小的功能性生物结构。为了实现这一目标，我们将开发、建模和验证新的生物打印方法，这些方法利用激光产生的微型喷射器来生物打印3D生物结构。具体目标是：(A)为激光打印生物墨水所涉及的物理机制开发一个完整的建模框架。(B)使用模型油墨对新型3D激光生物打印架构的性能进行实验验证和优化。(C)验证优化的3D激光生物打印架构，用于功能3D生物结构的逐层打印。拟议的计划可以实现与多种生物油墨配方兼容的生物打印工艺，并提供增强的打印后细胞生存能力。重要的是，它最终可能导致开发出负担得起的、占地面积小的生物打印设备，用于组织工程应用。在不久的将来，这些系统预计将被大量用于药物筛选模型，因为化合物可以在人体试验开始之前在生物打印组织上进行评估。

Bio-printing has emerged as one of the most influential applications of 3D printing, aiming to address the increased demand for living constructs with long term mechanical and biological stability suitable for transplantation, as well as improved drug discovery models. Existing 3D bio-printing technologies use electromechanical processes to deliver “inks” containing live cells, usually called bio-inks. Bio-inks are extremely sensitive to thermal and mechanical stress, thus existing bio-printing processes face the challenge of maintaining cell viability during the printing process. In this context, the long-term objective of my research is to address the ongoing demand for improved 3D bio-printing approaches, which are (i) compatible with both low and high viscosity bio-ink formulations, and (ii) capable to generate functional living constructs of biological relevant size with high resolution and speed. Towards this aim, we will develop, model, and validate novel bio-printing approaches that leverage laser-generated micro-jets to bio-print 3D living constructs. The specific aims are: (a) To develop a complete modeling framework for the physical mechanisms involved in laser printing of bio-inks. (b) To experimentally validate and optimize the performance of novel 3D laser bio-printing architectures by using model inks. (c) To validate optimized 3D laser bio-printing architectures for layer-by-layer printing of functional 3D living constructs. The proposed program can enable bio-printing processes that are compatible with a large variety of bio-ink formulations and offer enhanced post-printing cell viability. Importantly, it can eventually lead to the development of affordable, small-footprint bio-printing devices for tissue engineering applications. In the near future, those systems are expected to be heavily used for drug screening models, as compounds could be evaluated on bio-printed tissue before initiation of human trials.