MSM: Multiscale Mechanics of Bioengineered Tissues

描述（由申请人提供）：我们建议继续我们的生物工程组织的多尺度力学分析。在之前的资助期内，我们使用了双尺度模型，微观尺度通过离散网络表示胶原纤维，宏观尺度通过连续有限元表示组织整体；这两个尺度是完全耦合的，我们已经将该模型应用于各种系统。主要进展包括：(1)基于图像的模型生成方案；(2)双相分析，包括网络-流体和网络-固体系统；(3)单个纤维的动态修饰以表示酶降解或损伤；(4)纯凝胶（胶原蛋白）和共凝胶（胶原-琼脂糖和胶原-纤维蛋白）的实验研究。目前的模型已经非常成功，但在一个合适的工程组织材料科学可以说存在之前，还有更多的工作要做。在这次更新中，我们提出了三个主要的进展，将创建下一代生物工程组织的理论描述：(1)我们将通过第三个尺度将细胞力学添加到模型中。这三个尺度将代表组织，细胞-基质复合物

DESCRIPTION (provided by applicant): We propose to continue our multiscale mechanical analysis of bioengineered tissues. In the previous grant period, we used a two-scale model, with the microscopic scale representing collagen fibers via a discrete network and the macroscopic scale representing tissue as a whole via continuous finite elements; the two scales are fully coupled, and we have applied the model to a variety of systems. Major advances include (1) An image-based model generation scheme, (2) Biphasic analysis, including both network-fluid and network-solid systems, (3) Dynamic modification of individual fibers to represent enzymatic degradation or damage, and (4) Experimental studies of pure gels (collagen) and co-gels (collagen-agarose and collagen-fibrin). The current model has been extremely successful, but there is still more work to be done before a proper materials science of engineered tissues can be said to exist. In this renewal, we propose three major advances that will create the next generation theoretical description of a bioengineered tissue: (1) We will add cell mechanics to the model via a third scale. The three scales will represent the tissue, the cell-matrix composite with discrete cells, and the fiber matrix. This model will be a significant advance over existing models of cell-gel composites in that it will provide a mechanism to capture the internal mechanics of the matrix and to explore a wide range of cytomechanical models. (2) We will extend our initial model of fiber failure into a model that can capture progressive damage to the fibers and damage to the interfibrillar material, the latter potentially important because of the high strength of collagen relative to many other ECM components. (3) We will supplement our existing model with viscoelastic terms due to the fiber network, the interfibrillar material, and he cells, as well as add an extra water phase to the model to account for the effect of interstitial flow through the interfibrillar materials (extending our earlier biphasic models). The first advanc will address tissue complexity but remains prefailure and quasistatic. The second will allow the study of failing or damaged systems, and the third will capture dynamic tissue behavior. All three proposed theoretical advances will be combined with experiments to specify and test the models. Tissue engineering, the creation of replacements for damaged or diseased tissues, is an important area, especially for mechanical tissues such as artery, heart valve, and skin. A major impediment to advances in tissue engineering, especially to the creation and use of wholly bioengineered tissues, is our inability to design tissues as we design other engineered products. This project relates directly to public health because it will provide tools to help creae the next generation of replacement tissues.