Engineering Pulmonary Valve Tissue for Pediatric Patients with Tetralogy of Fallot

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Children born with congenital heart diseases, such as tetralogy of Fallot, often have defectiveheart valves. For example, in tetralogy of Fallot, the pulmonary artery and valve are narrowed.Surgeons can enlarge the artery and add a valve leaflet by using a patch made frompericardial tissue from around the heart or a synthetic fabric. While this provides temporaryrelief to the infant or child, the repair materials cannot grow with the patient and are prone toscarring and calcification, leading to a lifetime of reoperations and clinical interventions for thepatient.Here, we propose to use principles of heart valve tissue engineering to produce sheets ofliving valve leaflet tissue that can be used as an alternative repair material. The sheets will bemade from stem cells from the infants own umbilical cord grown on a polyurethane mesh,which will eventually dissolve away in the body to harmless byproducts, leaving behind aliving valve leaflet produced by the stem cells. To kickstart tissue production, we will first growthe valve tissue in bioreactors that exercise the tissue to improve its strength and flexibility.Most engineered valve tissue fails by scarring, so to prevent this, we will inject nanoparticlesloaded with an anti-scarring drug into the tissue prior to implantation. We will test this novelreplacement tissue in pigs to assess whether the material is durable, does not scar, andremains functional in the body.Over the next three years, our interdisciplinary team of material scientists, heart valveexperts, and cardiac surgeons will train next-generation engineers, scientists, and surgeonsand will collaborate with our partners at SickKids Hospital and Tissue RegenerationTherapuetics to translate this novel concept in congenital heart defect repair towards practice,significant improvement in the current standard of care, and economic impact throughcommercialization.