Design of self-assembling bio-inks for cell-based 3D printing

非技术性：3D打印是一个快速发展的领域，旨在为广泛的应用创造非常精确的复杂三维结构。目前，塑料的3D打印是一个相对常见的过程，通常可以在公共图书馆或服务中心以象征性的费用获得。3D打印在生物学和医学领域具有巨大的应用潜力。例如，使用3D打印机，可以在单个培养皿中创建具有精确几何形状的多种细胞类型的结构，以复制人体器官中存在的细胞相互作用类型。这些工程组织可以在体外用于预测不同类型的药物如何与人体相互作用，或者可以在体内用于替换受损组织。然而，使用这种技术来打印含细胞材料仍然是一个困难的挑战。这在一定程度上是由于生物墨水的不可用性，生物墨水既与细胞相容，又具有可打印所需的物理和化学性质。在这里，PI计划开发一系列具有打印所需特性的生物墨水，以及在打印过程中和之后保护细胞并保持其活力的能力。该项目有可能开发出一种新颖，复杂的生物墨水材料家族，可能具有巨大的治疗效果。此外，女性和代表性不足的少数民族（URM）研究生和本科生将被介绍给各种科学职业以及这些职业可能需要的技能。该项目还将促进斯坦福大学3D生物打印设施的建立，该设施将向本科生和研究生介绍工程领域的新工艺。技术：虽然热塑性塑料的3D打印现已成为常规，但用于生物技术和医学应用的载有细胞的聚合物结构的快速原型制作仍仅限于专业研究实验室。阻止基于细胞的3D打印广泛使用的一个关键限制是缺乏合适的生物墨水，这些生物墨水是细胞相容的，并且具有打印所需的物理化学性质。在这里，PI计划（1）设计一种新型生物材料家族，其具有可调的生物化学和机械特性，具有适当的物理化学特性，可用作载有细胞的生物墨水，（2）探索两阶段交联策略，以在流动期间提供机械屏蔽并提高打印结构的分辨率，以及（3）开放通道构建体内多种生化和机械线索的空间模式化以指导细胞行为。在这个项目的过程中，妇女和代表性不足的少数民族（URM）研究生和本科生将被介绍给各种STEM职业以及他们可能需要通过访问当地高中，高中科学教师的3D打印模块的准备，和暑期实习生研究经验的技能。此外，通过在斯坦福大学建立3D生物打印设施，本科生和研究生将接受3D生物打印以及新型材料设计和生产过程的培训，为他们进入工程职业道路做好准备。

Non-technical:3D printing is a fast-growing field that aims to create intricate three-dimensional structures of very precise specifications for a broad range of applications. Currently, 3D printing of plastic is a relatively common process and is often available in public libraries or service centers for a nominal fee. 3D printing has tremendous potential for applications in biology and medicine. For example, with a 3D printer, one could create structures of multiple cell types placed together with a precise geometry in a single Petri dish to replicate the types of cell interactions that are present in human organs. These engineered tissues could be used outside of the body to predict how different types of drugs may interact with humans or could be used inside the body to replace damaged tissues. However, the use of this technique to print cell-containing materials remains a difficult challenge. This is in part due to the unavailability of bio-inks that are both cell-compatible and have the physical and chemical properties required to be printable. Here, the PIs plan to develop a family of bio-inks with the properties required for printing as well as the ability to protect cells and maintain their viability during and after the printing process. This project has the potential to develop a novel, sophisticated family of bio-ink materials that may have great therapeutic impact. Additionally, women and under-represented minority (URM) graduate and undergraduate students will be introduced to a variety of scientific careers as well as the skills that may be required for these careers. This award will also facilitate the establishment of a 3D bio-printing facility at Stanford University, which will introduce students at the undergraduate and graduate level to novel processes in the field of engineering.Technical:While 3D printing of thermoplastics is now routine, the rapid prototyping of cell-laden, polymeric constructs for biotechnology and medical applications is still restricted to specialized research laboratories. A key limitation preventing the widespread use of cell-based 3D printing is the lack of suitable bio-inks that are cell-compatible and have the required physico-chemical properties for printing. Here, the PIs plan (1) the design of a novel family of biomaterials with tunable biochemical and mechanical properties with the appropriate physico-chemical properties for use as cell-laden bio-inks, (2) the exploration of a two-stage crosslinking strategy to provide mechanical shielding during flow and to improve the resolution of printed structures, and (3) the spatial patterning of multiple biochemical and mechanical cues within an open-channel construct to guide cell behavior. During the course of this project, women and under-represented minority (URM) graduate and undergraduate students will be introduced to a variety of STEM careers as well as the skills that they may require through visits to local high schools, preparation of a 3D printing module for high school science teachers, and a summer intern research experience. Additionally, through the establishment of a 3D bio-printing facility at Stanford University, students at the undergraduate and graduate levels will be trained in the process of 3D bio-printing and the design and production of novel materials, preparing them for entry into engineering career paths in the workforce.