Kojic M, Milosevic M, Simic V, Koay E J, Fleming J B, Nizzero S, Kojic N, Ziemys A, Ferrari M
Houston Methodist Research Institute, The Department of Nanomedicine, 6670 Bertner Ave., R7-117, Houston, TX 77030.
Bioengineering Research and Development Center BioIRC Kragujevac, Prvoslava Stojanovica 6, 3400 Kragujevac, Serbia.
Comput Methods Appl Mech Eng. 2017 Sep 1;324:413-437. doi: 10.1016/j.cma.2017.06.019. Epub 2017 Jun 29.
One of the key processes in living organisms is mass transport occurring from blood vessels to tissues for supplying tissues with oxygen, nutrients, drugs, immune cells, and - in the reverse direction - transport of waste products of cell metabolism to blood vessels. The mass exchange from blood vessels to tissue and vice versa occurs through blood vessel walls. This vital process has been investigated experimentally over centuries, and also in the last decades by the use of computational methods. Due to geometrical and functional complexity and heterogeneity of capillary systems, it is however not feasible to model individual capillaries (including transport through the walls and coupling to tissue) within whole organ models. Hence, there is a need for simplified and robust computational models that address mass transport in capillary-tissue systems. We here introduce a smeared modeling concept for gradient-driven mass transport and formulate a new composite smeared finite element (CSFE). The transport from capillary system is first smeared to continuous mass sources within tissue, under the assumption of uniform concentration within capillaries. Here, the fundamental relation between capillary surface area and volumetric fraction is derived as the basis for modeling transport through capillary walls. Further, we formulate the CSFE which relies on the transformation of the one-dimensional (1D) constitutive relations (for transport within capillaries) into the continuum form expressed by Darcy's and diffusion tensors. The introduced CSFE is composed of two volumetric parts - capillary and tissue domains, and has four nodal degrees of freedom (DOF): pressure and concentration for each of the two domains. The domains are coupled by connectivity elements at each node. The fictitious connectivity elements take into account the surface area of capillary walls which belongs to each node, as well as the wall material properties (permeability and partitioning). The overall FE model contains geometrical and material characteristics of the entire capillary-tissue system, with physiologically measurable parameters assigned to each FE node within the model. The smeared concept is implemented into our implicit-iterative FE scheme and into FE package PAK. The first three examples illustrate accuracy of the CSFE element, while the liver and pancreas models demonstrate robustness of the introduced methodology and its applicability to real physiological conditions.
生物体中的关键过程之一是物质从血管向组织的传输,为组织提供氧气、营养物质、药物、免疫细胞,以及在相反方向上,将细胞代谢的废物传输到血管。物质在血管和组织之间的交换通过血管壁进行。几个世纪以来,人们一直通过实验研究这一重要过程,在过去几十年中也利用计算方法进行研究。然而,由于毛细血管系统的几何形状和功能的复杂性及异质性,在整个器官模型中对单个毛细血管进行建模(包括通过血管壁的传输以及与组织的耦合)是不可行的。因此,需要简化且稳健的计算模型来处理毛细血管 - 组织系统中的物质传输。我们在此引入一种用于梯度驱动物质传输的模糊建模概念,并制定一种新的复合模糊有限元(CSFE)。在毛细血管内浓度均匀的假设下,首先将来自毛细血管系统的传输模糊为组织内的连续质量源。在此,推导了毛细血管表面积与体积分数之间的基本关系,作为对通过毛细血管壁的传输进行建模的基础。此外,我们制定了CSFE,它依赖于将一维(1D)本构关系(用于毛细血管内的传输)转换为由达西张量和扩散张量表示的连续体形式。引入的CSFE由两个体积部分组成——毛细血管和组织域,并且有四个节点自由度(DOF):两个域各自的压力和浓度。这些域通过每个节点处的连接单元耦合。虚拟连接单元考虑了属于每个节点的毛细血管壁的表面积以及壁材料特性(渗透率和分配系数)。整个有限元模型包含整个毛细血管 - 组织系统的几何和材料特性,模型中的每个有限元节点都分配了生理上可测量的参数。模糊概念被应用到我们的隐式迭代有限元方案以及有限元软件包PAK中。前三个例子说明了CSFE单元的准确性,而肝脏和胰腺模型展示了所引入方法的稳健性及其在实际生理条件下的适用性。