Engineering Pulmonary Valve Tissue for Pediatric Patients with Tetralogy of Fallot

患有先天性心脏病的儿童，如法洛四联症，通常有缺陷的心脏瓣膜。例如，法洛四联症，肺动脉和肺动脉瓣狭窄。外科医生可以使用由心脏周围的心包组织或合成织物制成的贴片扩大动脉并增加瓣叶。虽然这为婴儿或儿童提供了暂时的缓解，但修复材料不能随着患者生长而生长，并且容易形成疤痕和钙化，导致患者终身需要再手术和临床干预。在这里，我们建议使用心脏瓣膜组织工程的原理来生产可作为替代修复材料的活体瓣膜小叶组织片。这些薄片将由婴儿脐带的干细胞制成，这些干细胞生长在聚氨酯网上，最终会在体内溶解成无害的副产品，留下一个由干细胞产生的活瓣叶。为了启动组织生产，我们将首先在生物反应器中培养瓣膜组织，以锻炼组织以提高其强度和柔韧性。**大多数工程瓣膜组织因瘢痕形成而失效，因此为了防止这种情况，我们将在植入前向组织中注射含有抗瘢痕形成药物的纳米颗粒**。我们将在猪身上测试这种新型的替代组织，以评估这种材料是否耐用，不会留下疤痕，并在体内保持功能。在接下来的三年里，我们由材料科学家、心脏瓣膜专家和心脏外科医生组成的跨学科团队将培训下一代工程师、科学家和外科医生，并将与我们在SickKids医院和Tissue Regeneration therapeutics的合作伙伴合作，将这一先天性心脏缺陷修复的新概念转化为实践，**显着改善当前的护理标准，并通过**商业化产生经济影响。

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.