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Nanocomposite Hydrogel Bioinks for 3D Printing of Living Cells

用于活细胞 3D 打印的纳米复合水凝胶生物墨水

基本信息

批准号：
1636288
负责人：
Kyungsuk Yum
金额：
$ 10万
依托单位：
University of Texas at Arlington
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：
2016-09-01 至 2019-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1636288&HistoricalAwards=false
关键词：
Nanocomposite Hydrogel Bioinks 3D Printing

项目摘要

3D printing of living cells, or 3D bioprinting, holds great promise to build 3D tissues and, ultimately, organs. However, despite recent advances in 3D printing of non-biological materials, 3D printing of living cells remains a challenge. One of the key challenges is the lack of bioinks with 3D printability and biocompatibility. This award supports fundamental research on nanocomposite hydrogel bioinks that encapsulate living cells in 3D printing process. Results from this research will enable not only the rational design of cell-encapsulating bioinks with 3D printability and biocompatibility, but also the high resolution 3D printing of tissue structures. This research potentially benefits many areas in biomedicine, including the development of tissue and organ models, tissue engineering, and regenerative medicine.The research objectives of this project are (1) to understand the effects of compositions of cell-laden nanocomposite bioinks on their dynamic mechanical properties (shear-thinning and self-healing properties) and cell viability; and (2) to establish the relationship between the dynamic mechanical properties of cell-laden nanocomposite bioinks and their 3D printability and cell-compatibility (cell viability in printed tissues). To achieve the first objective, gel-phase nanocomposite bioinks that consist of surface-functionalized single-walled carbon nanotubes, gelatin methacrylate (hydrogel matrix), and living cells will be synthesized. The concentration of nanotubes and gelatin methacrylate will be varied from 0 to 10% with the total solid fraction of less than 10%. Fibroblasts and mesenchymal stem cells (10^6 to 10^8 cells/mL) will be used as model cells. The storage and loss shear moduli of these gel-phase bioinks will be measured with oscillatory strain sweeps and strain steps (thixotropy) using a rheometer to determine the shear-thinning and self-healing properties. The viability of cells encapsulated in bioinks will be measured (hourly and daily up to 7 days). To achieve the second objective, multilayer 3D tissue structures will be printed with 100 and 200 micron nozzles. The 3D printability of gel-phase bioinks will be determined by characterizing printed structures (shape definition and structural integrity) using optical microscopy. Bioinks that produce self-supporting 3D structures with a filament diameter of less than 200 microns will be defined as 3D printable. The cell-compatibility of nanocomposite bioinks will be determined by measuring the viability of cells in printed tissues (daily up to 7 days).

活细胞的3D打印，或3D生物打印，在构建3D组织以及最终制造器官方面有着巨大的前景。然而，尽管非生物材料的3D打印最近取得了进展，但活细胞的3D打印仍然是一个挑战。其中一个关键挑战是缺乏可3D打印和生物兼容性的生物墨水。该奖项支持3D打印过程中包裹活细胞的纳米复合水凝胶生物墨水的基础研究。本研究的结果不仅将使合理设计具有3D可打印性和生物相容性的细胞包裹型生物墨水，而且还将使组织结构的高分辨率3D打印成为可能。本课题的研究目标是(1)了解载细胞纳米复合生物墨水的组成对其动态力学性能(剪切稀释性和自愈性)和细胞存活率的影响；(2)建立载细胞纳米复合生物墨水的动态力学性能与其3D可打印性和细胞相容性(打印组织中的细胞存活率)之间的关系。为了实现第一个目标，将合成由表面功能化的单壁碳纳米管、明胶甲基丙烯酸酯(水凝胶基质)和活细胞组成的凝胶相纳米复合生物墨水。纳米管和明胶甲基丙烯酸酯的浓度将在0到10%之间变化，总固体分数将低于10%。以成纤维细胞和间充质干细胞(10^6~10^8个/毫升)作为模型细胞。这些凝胶相生物墨水的储存和损失剪切模数将通过振荡应变扫描和应变阶跃(触变性)使用流变仪测量，以确定剪切稀化和自愈性能。用生物墨水包裹的细胞的活力将被测量(每小时和每天，最多7天)。为了实现第二个目标，将用100微米和200微米的喷嘴打印多层3D组织结构。凝胶相生物墨水的3D可打印性将通过使用光学显微镜表征打印结构(形状定义和结构完整性)来确定。产生细丝直径小于200微米的自支撑3D结构的生物墨水将被定义为可3D打印。纳米复合生物墨水的细胞相容性将通过测量打印组织中细胞的活性来确定(每天最多7天)。