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心脏组织工程学和芯片上心脏的研究进展。

Advances in cardiac tissue engineering and heart-on-a-chip.

机构信息

Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.

Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.

出版信息

J Biomed Mater Res A. 2024 Apr;112(4):492-511. doi: 10.1002/jbm.a.37633. Epub 2023 Nov 1.

Abstract

Recent advances in both cardiac tissue engineering and hearts-on-a-chip are grounded in new biomaterial development as well as the employment of innovative fabrication techniques that enable precise control of the mechanical, electrical, and structural properties of the cardiac tissues being modelled. The elongated structure of cardiomyocytes requires tuning of substrate properties and application of biophysical stimuli to drive its mature phenotype. Landmark advances have already been achieved with induced pluripotent stem cell-derived cardiac patches that advanced to human testing. Heart-on-a-chip platforms are now commonly used by a number of pharmaceutical and biotechnology companies. Here, we provide an overview of cardiac physiology in order to better define the requirements for functional tissue recapitulation. We then discuss the biomaterials most commonly used in both cardiac tissue engineering and heart-on-a-chip, followed by the discussion of recent representative studies in both fields. We outline significant challenges common to both fields, specifically: scalable tissue fabrication and platform standardization, improving cellular fidelity through effective tissue vascularization, achieving adult tissue maturation, and ultimately developing cryopreservation protocols so that the tissues are available off the shelf.

摘要

近年来,心脏组织工程和芯片上心脏的发展都基于新的生物材料开发以及创新制造技术的应用,这些技术能够精确控制所模拟的心脏组织的机械、电气和结构特性。心肌细胞的长形结构需要调整基底特性并施加生物物理刺激,以驱动其成熟表型。已经取得了诱导多能干细胞衍生的心脏贴片的里程碑式进展,这些贴片已经进入人体测试阶段。现在,许多制药和生物技术公司都在使用芯片上心脏平台。在这里,我们提供了心脏生理学的概述,以便更好地定义功能组织再现的要求。然后,我们讨论了在心脏组织工程和芯片上心脏中最常用的生物材料,接着讨论了这两个领域的最新代表性研究。我们概述了这两个领域共同面临的重大挑战,特别是:可扩展的组织制造和平台标准化、通过有效的组织血管化提高细胞保真度、实现成人组织成熟以及最终开发冷冻保存方案,以便随时获得组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef87/11213712/96a87684afb7/nihms-1996094-f0001.jpg

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