Grant: Collaborative Health Research Projects (NSERC partnered)

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 infant's 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.