Computational Prediction of Mechanical and Transport Response Evolution in Degrading Porous Scaffolds

通过组织工程恢复活组织功能对医学的变革进步至关重要。组织工程材料必须具有生物相容性，并且通常以可控的方式可生物降解。例如，被切断的周围神经可以再生，但新的突起必须通过组织支架得到适当的滋养和引导。支架必须具有适合细胞生长的正确形态，适合滋养细胞的正确运输特性，以及在降解和组织再生过程中保持柔顺和完整的正确机械特性。可生物降解的支架很有吸引力，因为它们不需要通过手术移除；但它们只有在退化与神经再生同步时才有效。这只是组织工程面临的巨大挑战的众多例子之一。该奖项将产生基于物理、数学、聚合物化学和图像分析的多尺度方法，以预测和询问在程序化酶降解过程中多孔聚合物支架的运输和机械性能的演变。该项目对力学进步的贡献是一种新的方法来建模，从而理解具有神经组织工程等微观结构演变的多功能材料的行为。通过适当级别的神经科学力学应用研讨会，以及让本科生参与大脑生物力学课程的创建，教育部分包括吸引代表性不足的少数民族进入工程领域。生物可降解组织工程系统是具有复杂流固相互作用的可变形化学反应多孔混合物。该项目将特定的现有平均技术与原始的流固相互作用方法相结合，以确定在大变形和机械载荷下降解多孔聚合物网络的耦合力学和输运特性。与该项目相关的模型系统是交联聚氨酯掺杂聚酯，这是一种具有高度可控性的神经再生支架材料。这种材料将被建模为随机聚合物网络。样品将通过电子显微镜进行分析，以量化网络的形态。微观水平的输运和机械性能将通过聚合物网络结构的统计表征来确定。该过程将定义微观结构精确的代表性体积单元，然后可以通过一种基于流体-结构相互作用的新型有限元均匀化程序来分析由于降解而演变的微观结构。这个数值方案将在中尺度上作为退化的函数产生有效的力学和输运特性。力学的一个重要进步是，通过扩展浸入式有限元法（一种最先进的流固相互作用计算方法）来解释流体在微观结构不断变化的物体中的流动，将均质化问题作为流固相互作用问题的框架。该项目包括验证预测性质的实验。不同降解阶段的材料样品和全尺寸支架将在形态、弹性模量和扩散率方面进行表征，并将这些特性与相应的数值估计进行比较。

Restoring living tissue functionality via tissue engineering is crucial for transformative advances in medicine. Tissue engineering materials must be biocompatible and often biodegradable in a controlled manner. For example, severed peripheral nerves can regrow, but new projections must be properly nourished and guided via tissue scaffolds. Scaffolds must have the right morphology for cell growth, the right transport properties for nourishing cells, and the right mechanical properties to stay compliant and integral during degradation and tissue regeneration. Biodegradable scaffolds are appealing because they need not be surgically removed; but they are effective only if degradation is synchronized with nerve regrowth. This is but one of many examples illustrating the extraordinary challenges in tissue engineering. This award will yield a multi-scale approach based on physics, mathematics, polymer chemistry, and image analysis to predict and interrogate evolving transport and mechanical properties of porous polymeric scaffolds during programmed enzymatic degradation. The contribution of the project to the advancement of mechanics is a new methodology to model, and thus understand, the behavior of multi-functional materials with evolving microstructure like those in nerve tissue engineering. An educational component is included to attract underrepresented minorities to engineering via level-appropriate workshops on applications of mechanics in neuroscience, and by involving undergraduates in the creation of coursework for courses in brain biomechanics.Biodegradable tissue engineering systems are deformable chemically-reacting porous mixtures with complex fluid-structure interaction. The project integrates specific existing averaging techniques with an original fluid-structure interaction approach to determine the coupled mechanical and transport properties of degrading porous polymer networks subjected to large deformation and mechanical loadings. The model system of relevance to the project is crosslinked urethane-doped polyester, a promising scaffold material for nerve regeneration with highly controllable porosity. This material will be modeled as a random polymer network. Samples will be analyzed via electron microscopy to quantify the network's morphology. Microscopic-level transport and mechanical properties will be determined via a statistical characterization of the polymer network structure. This process will define microstructurally accurate representative volume elements whose evolution can then be analyzed via a novel finite element fluid-structure interaction-based homogenization procedure for evolving microstructure due to degradation. This numerical scheme will yield effective mechanical and transport properties at the mesoscale as a function of degradation. A crucial advancement in mechanics is the framing of the homogenization problem as a fluid-structure interaction problem, by extending the immersed finite element method (a state-of-the-art fluid-structure interaction computational approach) to account for fluid flow through bodies with evolving microstructure. The project includes experiments to validate predicted properties. Material samples and full-scale scaffold at different stages of degradation will be characterized in terms of morphology, elastic moduli, and diffusivity, and these properties compared to corresponding numerical estimates.