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使用 3D 生物打印明胶图案水凝胶进行心脏组织工程的接触指导。

Contact guidance for cardiac tissue engineering using 3D bioprinted gelatin patterned hydrogel.

机构信息

Division of Materials Technology, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue 639798, Singapore.

出版信息

Biofabrication. 2018 Jan 12;10(2):025003. doi: 10.1088/1758-5090/aaa15d.

Abstract

Here, we have developed a 3D bioprinted microchanneled gelatin hydrogel that promotes human mesenchymal stem cell (hMSC) myocardial commitment and supports native cardiomyocytes (CMs) contractile functionality. Firstly, we studied the effect of bioprinted microchanneled hydrogel on the alignment, elongation, and differentiation of hMSC. Notably, the cells displayed well defined F-actin anisotropy and elongated morphology on the microchanneled hydrogel, hence showing the effects of topographical control over cell behavior. Furthermore, the aligned stem cells showed myocardial lineage commitment, as detected using mature cardiac markers. The fluorescence-activated cell sorting analysis also confirmed a significant increase in the commitment towards myocardial tissue lineage. Moreover, seeded CMs were found to be more aligned and demonstrated synchronized beating on microchanneled hydrogel as compared to the unpatterned hydrogel. Overall, our study proved that microchanneled hydrogel scaffold produced by 3D bioprinting induces myocardial differentiation of stem cells as well as supports CMs growth and contractility. Applications of this approach may be beneficial for generating in vitro cardiac model systems to physiological and cardiotoxicity studies as well as in vivo generating custom designed cell impregnated constructs for tissue engineering and regenerative medicine applications.

摘要

在这里,我们开发了一种 3D 生物打印的微通道明胶水凝胶,它可以促进人骨髓间充质干细胞(hMSC)向心肌细胞分化,并支持原代心肌细胞(CMs)的收缩功能。首先,我们研究了生物打印微通道水凝胶对 hMSC 排列、伸长和分化的影响。值得注意的是,细胞在微通道水凝胶上表现出明确的 F-肌动蛋白各向异性和伸长形态,因此显示出对细胞行为的形貌控制的效果。此外,排列的干细胞表现出心肌谱系的分化,这可以通过成熟的心脏标志物检测到。荧光激活细胞分选分析也证实了向心肌组织谱系的显著分化。此外,与无图案水凝胶相比,在微通道水凝胶上发现接种的 CMs 排列更整齐,并表现出同步跳动。总的来说,我们的研究证明了 3D 生物打印产生的微通道水凝胶支架可以诱导干细胞向心肌细胞分化,并支持 CMs 的生长和收缩性。这种方法的应用可能有益于生成体外心脏模型系统,用于生理和心脏毒性研究,以及体内生成用于组织工程和再生医学应用的定制设计的细胞浸渍构建体。

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