GOALI: Printing of Heterogeneous Tissue Constructs from Reactive Biomaterials using Intersecting Jets

GOALI：使用相交喷射机打印反应性生物材料的异质组织结构

• 批准号: 1634755
• 负责人: Yong Huang
• 金额: $ 30万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1634755&HistoricalAwards=false
• 关键词: GOALI; Printing; Heterogeneous; Tissue; Constructs

Inkjet bioprinting is an additive manufacturing approach for creating 3D tissue constructs using cell suspensions and hydrogels as bioinks. Many hydrogels and cell suspensions can be mixed to prepare cell-laden bioinks for traditional mixing-then-printing applications. However, some hydrogels are chemically reactive with cell suspensions upon mixing. Bioinks prepared by mixing these hydrogels and cell suspensions have significantly deteriorated printability and even are not printable at all. This GOALI award supports fundamental research on a mixing-while-printing approach to print reactive hydrogels and cell suspensions. Results from this research will expand the versatility of 3D inkjet bioprinting with reactive biomaterials. Printed heterogeneous tissue constructs can be used as organ models for various biomedical applications such as drug screening, and might be used for organ transplantation in the future.With the mixing-while-printing approach, reactive hydrogels and cell suspensions are printed as two individual jets; the jets break up, intersect, and mix with each other due to droplet collision and coalescence, resulting in a gelled heterogeneous building block. The research objectives are two-fold: (1) to understand the effects of printing conditions on droplet formation, impingement, collision, and coalescence processes when using intersecting jets; and (2) to elucidate the influences of droplet impingement, collision, and coalescence on the material mixing performance during mixing-while-printing biofabrication. To achieve the first objective, cell-laden droplet formation process will be modeled using a volume of fluid-based computational approach to predict the droplet morphology, size, and velocity under different nozzle diameters and exciting voltages. Droplet impingement, collision, and coalescence processes will be modeled using a meshfree smooth particle hydrodynamic method under different intersecting angles and standoff distances. Some model predictions will be compared with experimental results, and the droplet morphology, size, and velocity before and after jet intersecting will be measured using high speed imaging. To achieve the second objective, material mixing performance will be evaluated in terms of how living cells are distributed in a printed structure. The mixing performance will be modeled using a set of material property and printing condition-related dimensionless numbers based on a scale analysis of governing conservation equations and interfacial conditions. Predicted mixing performance will be compared with the measured cell distribution of deposited droplets and fabricated tissue constructs using particle image velocimetry and optical imaging, respectively, under different droplet impingement, collision, and coalescence scenarios.

喷墨生物打印是一种增材制造方法，用于使用细胞悬浮凝胶和水凝胶作为生物键创建3D组织构建体。许多水凝胶和细胞悬浮液可以混合，以制备传统混合使用细胞的生物互联，然后打印出印刷的应用。但是，一些水凝胶在混合后具有化学反应性，细胞悬浮液。通过混合这些水凝胶和细胞悬浮液来制备的生物键具有明显的可打印性，甚至根本不可打印。该目标奖支持对打印反应性水凝胶和细胞悬浮液的混合印刷方法的基础研究。这项研究的结果将扩大与反应性生物材料的3D喷墨生物打印的多功能性。印刷的异质组织构建体可以用作各种生物医学应用（例如药物筛查）的器官模型，并可能在将来用于器官移植。与混合打印方法，反应性水凝胶和细胞悬浮液一起被打印为两个单独的JET。由于液滴的碰撞和结合，喷气机分解，相交并相互混合，导致凝胶异质的构建块。研究目标是两个方面：（1）使用相交的喷气机时，要了解印刷条件对液滴形成，撞击，碰撞和结合过程的影响； （2）阐明液滴撞击，碰撞和聚结对混合时混合性能的影响。为了实现第一个目标，将使用基于流体的计算方法来对富含细胞的液滴形成过程进行建模，以预测不同喷嘴直径和令人兴奋的电压下的液滴形态，大小和速度。液滴撞击，碰撞和聚合过程将在不同的相交角度和隔离距离下使用网状平滑粒子流体动力学方法进行建模。一些模型预测将与实验结果进行比较，并且将使用高速成像来测量射流相交之前和之后的液滴形态，大小和速度。为了实现第二个目标，将根据如何在印刷结构中分布生物细胞来评估材料混合性能。混合性能将使用一组材料属性和印刷条件相关的无量纲数字进行建模，该数字基于管理保护方程和界面条件的比例分析。在不同的液滴撞击，碰撞和合并的情况下，分别将预测的混合性能与沉积液滴和制造组织构建体的细胞分布进行比较。

项目成果

Phase Diagram of Pinch-off Behaviors During Drop-on-Demand Inkjetting of Alginate Solutions

• DOI: 10.1115/1.4044252
• 发表时间: 2019-06
• 期刊: Journal of Manufacturing Science and Engineering
• 作者: Changxue Xu;Zhengyi Zhang;Yong Huang;Heqi Xu

Study of Layer Formation During Droplet-Based Three-Dimensional Printing of Gel Structures

• DOI: 10.1115/1.4036785
• 发表时间: 2017-09
• 期刊: Journal of Manufacturing Science and Engineering-transactions of The Asme
• 影响因子: 4
• 作者: Kyle Christensen;Yong Huang

Deformation Compensation During Buoyancy-Enabled Inkjet Printing of Three-Dimensional Soft Tubular Structures

• DOI: 10.1115/1.4037996
• 发表时间: 2018-01-01
• 期刊: JOURNAL OF MANUFACTURING SCIENCE AND ENGINEERING-TRANSACTIONS OF THE ASME
• 影响因子: 4
• 作者: Christensen, Kyle;Zhang, Zhengyi;Huang, Yong
• 通讯作者: Huang, Yong

Inkjet Bioprinting of 3D Silk Fibroin Cellular Constructs Using Sacrificial Alginate

• DOI: 10.1021/acsbiomaterials.6b00432
• 发表时间: 2017-08-01
• 期刊: ACS BIOMATERIALS SCIENCE & ENGINEERING
• 影响因子: 5.8
• 作者: Compaan, Ashley M.;Christensen, Kyle;Huang, Yong
• 通讯作者: Huang, Yong

Study of extrudability and standoff distance effect during nanoclay-enabled direct printing

• DOI: 10.1007/s42242-018-0009-y
• 发表时间: 2018-06-01
• 期刊: BIO-DESIGN AND MANUFACTURING
• 影响因子: 7.9
• 作者: Jin, Yifei;Zhao, Danyang;Huang, Yong
• 通讯作者: Huang, Yong