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 defective**heart 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 from**pericardial tissue from around the heart or a synthetic fabric. While this provides temporary**relief to the infant or child, the repair materials cannot grow with the patient and are prone to**scarring and calcification, leading to a lifetime of reoperations and clinical interventions for the**patient.**Here, we propose to use principles of heart valve tissue engineering to produce sheets of**living valve leaflet tissue that can be used as an alternative repair material. The sheets will be**made 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 a**living valve leaflet produced by the stem cells. To kickstart tissue production, we will first grow**the 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 nanoparticles**loaded with an anti-scarring drug into the tissue prior to implantation. We will test this novel**replacement tissue in pigs to assess whether the material is durable, does not scar, and**remains functional in the body.**Over the next three years, our interdisciplinary team of material scientists, heart valve**experts, and cardiac surgeons will train next-generation engineers, scientists, and surgeons**and will collaborate with our partners at SickKids Hospital and Tissue Regeneration**Therapuetics to translate this novel concept in congenital heart defect repair towards practice,**significant improvement in the current standard of care, and economic impact through**commercialization.