Evaluating the Growth Potential of Tissue Engineered Vascular Grafts: Role of
Vasoactivity and Active Endothelium to Altered Mechanical Stimuli
Kristin S. Miller Ph.D.1, Ramak Khosravi B.S.2, Christopher K. Breuer M.D.3, Jay D. Humphrey
Ph.D.2,4
1Tulane
University, New Orleans, LA, 2Yale University, New Haven, CT, 3Nationwide Children’s Hospital, Columbus,
OH, 4Yale School of Medicine, New Haven, CT
Continued advances in the tissue engineering of vascular grafts have enabled a paradigm shift
from the desire to design for adequate suture retention, burst pressure, and thrombo-resistance
to the goal of minimizing compliance mismatch between the grafts and adjacent vasculature.
Toward this end, we recently presented a modeling framework that predicts salient features of
neovessel evolution considering the monotonic loss of a load-bearing polymer scaffold and the
subsequent production of collagen and passive smooth muscle. We have shown that the
computational framework is amenable to evaluate compliance mismatch as well as to assess
the consequences of different scaffold parameters on neovessel formation. The growth potential
of vascular grafts to adapt to altered hemodynamics, however, has not yet been evaluated.
Vasoactivity and an active endothelium are thought to be integral to vascular adaptation.
Despite continued advances in vascular tissue engineering, however, experiments have not yet
yielded neovessels with active smooth muscle. Toward this end, in this study we evaluate in
silico the growth potential of interposition grafts, implanted within the murine venous circulation,
to altered hemodynamics and axial stretch following the formation of a neovessel (steady
remodeled state). Further, the potential contributions of active smooth muscle and an active
endothelium to neovessel adaptation are evaluated. We submit that growth and remodeling
models enable hypothesis-driven studies to evaluate different methods of graft failure (e.g., lack
of growth potential and compliance mismatch). Computational models should thus be viewed as
valuable tools to screen scaffold designs and guide experiments, and thus advance vascular
tissue engineering.