Computational Model-Driven Design of Tissue Engineered Vascular Grafts

Stanford Bio-X Frontiers in Interdisciplinary Biosciences Seminar
JAY HUMPHREY, YALE UNIVERSITY

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 [1] can be adapted to account for the in vitro development of a tissue engineered artery in a bioreactor [2] 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 [5]. Building on these prior successes, we are now focused on using formal methods of optimization to identify improved scaffolds.

References

1. Humphrey, J.D., Rajagopal, K.R., (2002) Math Model Meth Appl Sci 12, p407.
2. Niklason, L.E., et al. (2010) Proc Nat Acad Sci USA 107, p3335.
3. Miller, K.S., et al. (2014) J Biomech 47, p2080.
4. Miller, K.S., et al. (2015) Acta Biomat 11, p283.
5. Khosravi, R., et al. (2015) Tiss Engr A 21, p1529.

April 12th, 2018 at 12:15 PM in Clark Center Seminar Room S360

Hosted by:

Alison Marsden, Associate Professor of Pediatrics and Bioengineering, Stanford University

Pre-Seminar April 10th, 2018 at 12:15 PM in Clark S361