COMPUTATIONAL GROWTH AND REMODELING MODEL FOR EVOLVING TISSUE ENGINEERED VASCULAR GRAFTS IN THE VENOUS CIRCULATION

摘要

The field of vascular tissue engineering continues to advance rapidly, yet there is a pressing need to understand better the time course of polymer degradation and the sequence of cell-mediated matrix deposition and organization. Mounting evidence suggests that cells respond to mechanical perturbations through a process of growth and remodeling (G&R) to establish, maintain, and restore a preferred state of homeostatic stress. Previous computational models utilizing G&R approaches have captured arterial responses to diverse changes in mechanical loading [1, 8, 9]. Recently, a G&R framework was also introduced to account for the kinetics of polymer degradation as well as synthesis and degradation of neotissue constituents [5]. Niklason et al. demonstrated that models of G&R can predict both evolving tissue composition and mechanical behavior after extended periods of in vitro culture of polymer-based tissue-engineered vascular grafts (TEVGs), thus providing insights into the timecourse of neotissue formation and polymer removal. Moreover, they suggest that models of G&R can be powerful tools for the future refinement and optimization of scaffold designs. Nevertheless, such computational models have not yet been developed for examining the formation of neotissue following the implantation of a polymeric TEVG in vivo. Previously, Roh et al. [6] demonstrated the potential of TEVGs composed of nonwoven sheets of polyglycolic acid sealed with a copolymer of poly-L-lactide and -ε-caprolactone PGA/P(CL/LA) for high flow, low pressure applications. Follow up studies investigating the formation of neotissue suggested that the TEVGs transform into functional neotissues via an inflammatory-mediated process of vascular remodeling [2,7]. A theoretical framework to account for both stress- and inflammation-mediated G&R has not yet been developed. Finally, a recent study characterized the biomechanical properties of the degrading PGA-P(CL/LA) scaffold and evolving neotissue composite TEVG in the venous circulation using a murine model [4].