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

通过组织工程恢复活组织的功能对医学的变革性进步至关重要。组织工程材料必须是生物相容的，而且通常是可控制的生物降解材料。例如，切断的周围神经可以再生，但新的投射必须通过组织支架得到适当的营养和引导。支架必须具有适合细胞生长的合适的形态，适合滋养细胞的运输特性，以及合适的机械特性，以便在降解和组织再生过程中保持顺应性和完整性。生物可降解支架很有吸引力，因为它们不需要通过手术移除；但只有在降解与神经再生同步的情况下，它们才有效。这只是许多例子中的一个，说明了组织工程中的非凡挑战。该奖项将产生一种基于物理、数学、聚合物化学和图像分析的多尺度方法，以预测和询问多孔聚合物支架在编程酶降解过程中不断演变的运输和机械性能。该项目对力学进步的贡献是一种新的方法来模拟和理解具有演变微结构的多功能材料的行为，如神经组织工程中的材料。包括一个教育部分，通过神经科学中力学应用的适当水平的研讨会，并通过让本科生参与脑生物力学课程的创建，来吸引代表不足的少数族裔进入工程学。生物可降解组织工程系统是可变形的化学反应的多孔混合物，具有复杂的流体-结构相互作用。该项目将现有的特定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的多孔性聚合物网络的耦合力学和传输特性。与该项目相关的模型系统是交联型氨基甲酸酯掺杂聚酯，这是一种具有高度可控孔隙率的有望用于神经再生的支架材料。这种材料将被建模为随机的聚合物网络。样品将通过电子显微镜进行分析，以量化网络的形态。微观层面的传输和机械性能将通过聚合物网络结构的统计特征来确定。这一过程将定义微观结构上精确的代表性体积元素，然后可以通过一种新的基于有限元流固耦合的均化过程来分析这些体积元素的演化，以研究由于退化而产生的微观结构的演变。这种数值格式将在中尺度上产生有效的力学和输运性质，作为退化的函数。力学上的一个重要进展是，通过扩展浸没有限元方法(一种最先进的流固耦合计算方法)来考虑流体在具有不断变化的微观结构的物体中的流动，将均化问题框架化为流固耦合问题。该项目包括验证预测特性的实验。材料样品和不同降解阶段的足尺支架将在形态、弹性模量和扩散系数方面进行表征，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.