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

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.