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可3D打印的甲基丙烯酸明胶-黄原胶水凝胶生物墨水可使人诱导多能干细胞分化为心肌细胞。

3D-Printable Gelatin Methacrylate-Xanthan Gum Hydrogel Bioink Enabling Human Induced Pluripotent Stem Cell Differentiation into Cardiomyocytes.

作者信息

Deidda Virginia, Ventisette Isabel, Langione Marianna, Giammarino Lucrezia, Pioner Josè Manuel, Credi Caterina, Carpi Federico

机构信息

Department of Industrial Engineering, University of Florence, 50139 Florence, Italy.

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.

出版信息

J Funct Biomater. 2024 Oct 5;15(10):297. doi: 10.3390/jfb15100297.

DOI:10.3390/jfb15100297
PMID:39452595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11508550/
Abstract

We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using a gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at a low concentration (5% /) allows for the growth of diverse cells, its 3D printability has been found to be limited by its low viscosity. To overcome that drawback, making the hydrogel both compatible with hiPSCs and 3D-printable, we developed an extrudable GelMA-based bioink by adding xanthan gum (XG). The GelMA-XG composite hydrogel had an elastic modulus (9 kPa) comparable to that of cardiac tissue, and enabled 3D printing with high values of printing accuracy (83%) and printability (0.98). Tests with hiPSCs showed the hydrogel's ability to promote their proliferation within both 2D and 3D cell cultures. The tests also showed that hiPSCs inside hemispheres of the hydrogel were able to differentiate into cardiomyocytes, capable of spontaneous contractions (average frequency of ~0.5 Hz and amplitude of ~2%). Furthermore, bioprinting tests proved the possibility of fabricating 3D constructs of the hiPSC-laden hydrogel, with well-defined line widths (800 μm).

摘要

我们描述了一种生物墨水的研发,该生物墨水用于使用基于甲基丙烯酸明胶(GelMA)的水凝胶对人类诱导多能干细胞(hiPSC)进行生物打印,以用于可能的心脏组织工程。虽然先前的研究表明,低浓度(5%)的GelMA能够支持多种细胞生长,但其3D打印性已被发现因其低粘度而受到限制。为了克服这一缺点,使水凝胶既与hiPSC兼容又可3D打印,我们通过添加黄原胶(XG)开发了一种可挤出的基于GelMA的生物墨水。GelMA-XG复合水凝胶的弹性模量(约9 kPa)与心脏组织相当,并实现了具有高打印精度(83%)和可打印性(0.98)的3D打印。对hiPSC的测试表明,该水凝胶能够在2D和3D细胞培养中促进其增殖。测试还表明,水凝胶半球内的hiPSC能够分化为心肌细胞,能够自发收缩(平均频率约为0.5 Hz,幅度约为2%)。此外,生物打印测试证明了制造载有hiPSC的水凝胶的3D构建体的可能性,其线宽明确(约800μm)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/8a6b39514f1c/jfb-15-00297-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/0767f21d557d/jfb-15-00297-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/68566d8376eb/jfb-15-00297-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/caff93cdaff1/jfb-15-00297-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/6c7a377915de/jfb-15-00297-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/8a6b39514f1c/jfb-15-00297-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/0767f21d557d/jfb-15-00297-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/213754276f28/jfb-15-00297-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/c63df9277b6b/jfb-15-00297-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/68566d8376eb/jfb-15-00297-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/e6b1a145b260/jfb-15-00297-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/caff93cdaff1/jfb-15-00297-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/6c7a377915de/jfb-15-00297-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/11508550/8a6b39514f1c/jfb-15-00297-g010.jpg

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