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Abstract：
Tissue engineering, with the goal of repairing or replacing damaged tissue and organs, has continued to make dramatic science-based advances since its origins in the late 1980\'s and early 1990\'s. Such advances are always multi-disciplinary in nature, from basic biology and chemistry through physics and mathematics to various engineering and computer fields. This review will focus its attention on two topics critical for tissue engineering liver development: (a) fluid flow, zonation, and drug screening, and (b) biomechanics, tissue stiffness, and fibrosis, all within the context of 3D structures. First, a general overview of various bioreactor designs developed to investigate fluid transport and tissue biomechanics is given. This includes a mention of computational fluid dynamic methods used to optimize and validate these designs. Thereafter, the perspective provided by computer simulations of flow, reactive transport, and biomechanics responses at the scale of the liver lobule and liver tissue is outlined, in addition to how bioreactor-measured properties can be utilized in these models. Here, the fundamental issues of tortuosity and upscaling are highlighted, as well as the role of disease and fibrosis in these issues. Some idealized simulations of the effects of fibrosis on lobule drug transport and mechanics responses are provided to further illustrate these concepts. This review concludes with an outline of some practical applications of tissue engineering advances and how efficient computational upscaling techniques, such as dual continuum modeling, might be used to quantify the transition of bioreactor results to the full liver scale.
摘要：
组织工程,目的是修复或更换受损的组织和器官，自20世纪80年代末和90年代初起源以来，一直在以科学为基础的巨大进步。这种进步本质上总是多学科的，从基础生物学和化学到物理和数学，再到各种工程和计算机领域。这篇综述将把注意力集中在对组织工程肝脏发育至关重要的两个主题上：（a）流体流动，分区,和药物筛选，和（b）生物力学，组织硬度,和纤维化，都在3D结构的背景下。首先,为研究流体运输和组织生物力学而开发的各种生物反应器设计的一般概述。这包括提及用于优化和验证这些设计的计算流体动力学方法。此后,计算机模拟流动提供的视角，反应性传输,概述了肝小叶和肝组织尺度的生物力学反应，除了如何在这些模型中利用生物反应器测量的特性。这里,突出了曲折和升级的基本问题，以及疾病和纤维化在这些问题中的作用。提供了纤维化对小叶药物转运和力学反应影响的一些理想化模拟，以进一步说明这些概念。这篇综述总结了组织工程进展的一些实际应用概述，以及如何有效地计算升级技术，例如双连续体建模，可用于量化生物反应器结果到整个肝脏规模的转变。
