Optimization of Tissue-Engineered Vascular Graft Design Using Computational Modeling

Abstract

Tissue-engineered vascular grafts hold great promise in many clinical applications, especially in pediatrics wherein growth potential is critical. A continuing challenge, however, is identification of optimal scaffold parameters for promoting favorable neovessel development. In particular, given the countless design parameters available, including those related to polymeric microstructure, material behavior, and degradation kinetics, the number of possible scaffold designs is almost limitless. Advances in computationally modeling the growth and remodeling of native blood vessels suggest that similar simulations could help reduce the search space for candidate scaffold designs in tissue engineering. In this study, we meld a computational model of in vivo neovessel formation with a surrogate management framework to identify optimal scaffold designs for use in the extracardiac Fontan circulation while comparing the utility of different objective functions. We show that evolving luminal radius and graft compliance can be matched to that of the native vein by the end of the simulation period with judicious combinations of scaffold parameters, although the inability to match these metrics at all times reveals constraints engendered by current materials. We emphasize further that there is yet a need to examine additional metrics, and combinations thereof, when seeking to optimize functionality and reduce the potential for adverse outcomes. Tissue-engineered vascular grafts have considerable promise for treating myriad conditions, and multiple designs are now in FDA-approved trials. Nevertheless, the search continues for the optimal design of the underlying polymeric scaffold. We present a novel melding of a computational model of vascular adaptation and a formal method of optimization that can aid in identifying optimal design parameters, with potential to save development time and costs while improving clinical outcomes.