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纤维增强凝胶支架引导 3D 打印心室中的心肌细胞排列。

Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles.

机构信息

Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, USA.

Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.

出版信息

Nat Mater. 2023 Aug;22(8):1039-1046. doi: 10.1038/s41563-023-01611-3. Epub 2023 Jul 27.

Abstract

Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol-gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties.

摘要

水凝胶是组织工程中极具吸引力的材料,但迄今为止的研究进展表明,水凝胶在产生促进细胞自组织成层次化三维(3D)器官模型所需的微观结构特征方面的能力有限。在这里,我们开发了一种含有预制明胶纤维的水凝胶墨水,用于打印 3D 器官级支架,这些支架再现了心脏的细胞内和细胞间组织。将预制明胶纤维添加到水凝胶中可以调整墨水的流变特性,从而实现可控的溶胶-凝胶转变,以实现无需额外支撑材料的独立 3D 结构的精确打印。在墨水挤出过程中纤维的剪切诱导排列提供了微尺度的几何线索,促进了培养的人心肌细胞在体外自组织成各向异性的肌肉组织。由此产生的 3D 打印心室体外模型表现出仿生各向异性的电生理和收缩性能。

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