Institute of Biomaterials Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
ACS Biomater Sci Eng. 2022 Jun 13;8(6):2144-2160. doi: 10.1021/acsbiomaterials.1c00636. Epub 2022 May 6.
Despite capturing the imagination of scientists for decades, the goal of creating an artificial heart for transplantation proved to be significantly more challenging than initially anticipated. Toward this goal, recent ground-breaking studies demonstrate the development of functional left ventricular (LV) models. LV models are artificially constructed 3D chambers that are capable of containing liquid within the engineered cavity and exhibit the functionality of native LV including contraction, ejection of fluid, and electrical impulse propagation. Various hydrogels and polymers have been used in manufacturing of LV models, relying on techniques such as electrospinning, bioprinting, casting, and molding. Most studies scaled down the models based on the dimensions of the human or rat ventricle. Initially, neonatal rat cardiomyocytes were the cell type of choice for construction the LV models. Yet, as the stem cell biology field advanced, recent studies focused on the use of cardiomyocytes derived from human induced pluripotent stem cells. In this review, we first describe the physiological characteristics of the human heart, to establish the parameter space for modeling. We then elaborate on current advances in the field and compare recently developed LV models among themselves and with the native human left ventricle. Fabrication methods, cell types, biomaterials, functional properties, and disease modeling capability are some of the major parameters that have distinguished these models. We also highlight some of the current challenges in this field, such as vascularization, cell composition and fidelity, and discuss potential solutions to overcome them.
尽管人工心脏的研究已经吸引了科学家们几十年的想象力,但事实证明,要将其成功应用于临床并移植到患者体内,远比最初预期的要困难得多。为了实现这一目标,最近的突破性研究展示了功能性左心室(LV)模型的发展。LV 模型是人工构建的 3D 腔室,能够在工程腔室内容纳液体,并表现出原生 LV 的功能,包括收缩、射液和电脉冲传播。在 LV 模型的制造中,已经使用了各种水凝胶和聚合物,并依赖于静电纺丝、生物打印、铸造和成型等技术。大多数研究都是基于人体或大鼠心室的尺寸对模型进行缩尺。最初,新生大鼠心肌细胞是构建 LV 模型的首选细胞类型。然而,随着干细胞生物学领域的发展,最近的研究集中在使用源自人类诱导多能干细胞的心肌细胞上。在这篇综述中,我们首先描述了人类心脏的生理特征,以确定建模的参数空间。然后,我们详细介绍了该领域的最新进展,并比较了最近开发的 LV 模型之间以及与原生人类左心室之间的差异。制造方法、细胞类型、生物材料、功能特性和疾病建模能力是区分这些模型的一些主要参数。我们还强调了该领域目前存在的一些挑战,例如血管化、细胞组成和保真度,并讨论了潜在的解决方案。