Publication:
SEED IT OR LEAVE IT: A LOOK AT CELL SEEDING EFFECTS ON TISSUE ENGINEERED VASCULAR GRAFTS

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Congenital heart disease is one of the most common causes of birth defect mortalities in infants. Reconstructive surgery is often the only form of treatment yet causes life-long complications for survivors. The reconstructive Fontan operation for congenital heart disease currently uses synthetic polytetrafluoroethylene (PTFE) vascular grafts. Although effective, PTFE grafts pose risks such as calcification and thrombosis, and cannot grow with the patient, which may necessitate multiple surgical interventions and ultimately affect long-term outcomes. Tissue engineered vascular grafts (TEVGs) are a promising alternative to PTFE grafts. TEVGs consist of a biodegradable polymer scaffold, which fully degrades within one year after implantation, leaving behind a neovessel formed from the patient’s own cells. Most importantly, TEVG neovessels can grow with the patient and self-repair, like native tissue. The main clinical complication precluding widespread adaptation of the TEVG is graft narrowing, or stenosis, which was determined to be inflammation driven. Currently, clinical TEVGs are seeded with the patient’s bone marrow mononuclear cells (BM-MNCs), which are believed to reduce graft immunogenicity and potentially reduce the incidence and severity of stenosis. However, this approach limits scalability in clinical settings and adds yet another operative procedure for the patients. Our goal is to understand the short- and long-term effects of cell seeding on TEVG neovessel growth and development. For this study, we assessed TEVG growth and degree of narrowing longitudinally with biomedical imaging in a large-animal ovine model. We determined that unseeded TEVGs had the same development profiles as cell seeded TEVGs. This suggests that we may be able to remove the need for cell seeding procedures in our clinical trial without compromising any aspect of TEVG development and remodeling. * - Husson University + - Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital
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