Modeling Diffusion-Based Transport for Drug Delivery From Fibrous Tissue Engineered Scaffolds
The development of advanced computing techniques has generated a shift out of the world contained solely in laboratories and into the world of computational modeling. These advanced methods help alleviate some of the burdens and overhead associated with the laboratory experience and allow researchers to garner substantial knowledge about the systems they work with. As tissue engineering researchers work at smaller and smaller scales (micro to nano), it becomes more difficult, costly, and time consuming to evaluate the effects of changes in the complex system. Tissue engineers are faced with trying to understand how factors such as biocompatibility, inflammatory response, cell infiltration and growth effect the long-term success of an engineered scaffold. The aims of this project were to develop a first-generation three-dimensional model designed to simulate the release of a stimuli (e.g., carbon monoxide, traditional synthetic drugs, growth factors) from an engineered fiber tissue scaffold, model the transport through fibrous material, and determine the fate of the material (via processes such as cellular uptake/consumption and vascular transport). That was accomplished through the creation of a two-part modeling system: one model that generates the simulated fibrous scaffold structure, and a second model that simulates the transport from the fibrous scaffold. The results of this two part model provide insight on the effects of changes in parameters such aa fiber diameter, fiber orientation, and diffusion mechanism on the concentration levels within the vasculature and the cells. For example, when simulating a vascular graft tissue scaffold, rotating the fiber mesh so that the fiber layers are perpendicular to the vasculature creates channeling that allows for faster diffusion of the stimuli into the vasculature. By contrast, when the fiber layers were parallel to the vasculature, minor disruptions in the diffusion path slowed diffusion across the scaffold. After additional validation studies, the foundation built by this modeling system allows researchers to explore these complex systems without the complications associated with lab work. Researchers could run thousands of perturbations before ever stepping foot into the lab, providing valuable insight and understanding that could help guide future work.