Computational Model-Driven Design of Tissue Engineered Vascular Grafts
The Fontan surgical procedure is used to treat children born with particular congenital heart defects, namely to provide a direct connection between the inferior vena cava and the right pulmonary artery. This procedure has proven successful in better oxygenating and delivering blood despite the absence of one ventricle. Synthetic conduits are useful, but they can lead to diverse complications and they cannot grow with the child. Tissue engineering promises to enable an improved vascular conduit and is in clinical trials in the USA. There is a need, however, to find an optimal scaffold design that can minimize possible post-operative complications.
We previously showed that a basic constrained mixture formulation of vascular growth and remodeling  can be adapted to account for the in vitro development of a tissue engineered artery in a bioreactor  and we have now adapted this approach to describe the in vivo degradation of a polymeric scaffold that enables neotissue formation as a Fontan conduit [3,4]. Briefly, we include inflammatory effects due to the foreign body response and account for a transition from an immuno-biological to a mechano-biological driven production of extracellular tissue. Simulations demonstratethat the model can be parameterized to describe the evolving geometry and material properties of a tissue engineered graft over 6 months in a murine model relevant to the low-pressure Fontan circulation. Importantly, the model was then found to predict well subsequent evolution over the next 18 months . Building on these prior successes, we are now focused on using formal methods of optimization to identify improved scaffolds.Professor Humphrey has over 30 years of experience in the field of continuum biomechanics, with primary interest in vascular mechanics and mechanobiology. Professor Humphrey's lab has considerable experience in the design and construction of novel computer-controlled multiaxial test systems, measurement of vascular tissue mechanical properties and in vivo hemodynamics, nonlinear constitutive formulations, and computational biomechanics (mainly finite elements). They have formulated a unique “Constrained Mixture Theory” for soft tissue growth and remodeling (G&R) that has provided significant insight into the biomechanics of arterial adaptations to altered hemodynamics as well as aneurysmal enlargement, vein graft maladaptation, and tissue engineered vascular graft development. They have developed a finite element model of the effects of pooled glycosaminoglycans within the aortic wall, a histopathological characteristic unique to thoracic aortic aneurysms and dissections, and a fluid-solid-interaction model of the aortic tree that enables hypothesis generation and testing as well as experimental design. Much of their work relies on mouse models of mechano- and immuno-mediated vascular remodeling, which they phenotype biomechanically and model computationally.