Vascular Regeneration - Approaches

Over the past two decades, we have pioneered techniques to engineer small-diameter blood vessels that are strong enough to withstand arterial blood flow. Such technology exploits the inherent ability of smooth muscle cells to secrete extracellular matrix and mimics mechanical conditions similar to the pulsatile nature of blood flowing through a vessel. Growing a blood vessel graft involves seeding smooth muscle cells on a polymer matrix over a silicone tube in a bioreactor in a growth medium that supports matrix secretion by the cells. Pulsing PBS through the silicone tube provides additional mechanical conditioning to promote matrix deposition. Over 8 to 10 weeks, the polymer degrades, while leaving behind a tubular construct of cells, and mostly collagenous matrix.

Vascular grafts have been created from various cell sources such as rodent, canine, porcine, and human, and have shown functionality in various in vivo models. We have further focused our efforts on improving this in-house technology, in order to improve our basic understanding of vascular biology while harnessing this knowledge for the development of novel solutions for clinical applications. Some areas that have been of interest to us include:

1. Decellularization techniques to make off-the-shelf grafts.
2. Novel bioreactor designs for improved mechanical conditioning.
3. Non-invasive imaging techniques to monitor vessel growth.
4. Novel cell sources for growing vascular grafts.
5. Development of anti-thrombogenic coatings.

We are also focused on the interaction between endothelial cells (ECs) and smooth muscle cells (SMCs) in tissue engineered blood vessels and vein grafts. A functional EC coverage in the vessel lumen is crucial to prevent excessive SMC proliferation and thrombosis. Changes in EC characteristics due to adaptation to different hemodynamic conditions may result in vessel failure because of increased SMC proliferation, matrix production and inward vessel growth (intimal hyperplasia). Mehmet’s aim is to culture vessels in bioreactors under arterial flow conditions to study the effects of different types of stem cell-derived ECs on SMC behavior and vessel remodeling. Findings of his study will provide helpful information to control SMC phenotype and maintain functional structure in engineered blood vessels.