Targeted LystaMab Therapy to Optimize Tissue Engineered Vascular Graft Performance

Project Description Despite significant advances in the surgical and medical management of congenital heart diseasecongenital cardiac anomalies remain a leading cause of death in the newborn periodMost severe forms of congenital heart disease require surgical interventionComplications arising from the use of currently available prosthetic materials in the form of vascular graftspatchesor replacement heart valves are a leading source of morbidity and mortality after congenital heart surgeryCurrently available prosthetic materials such as polytetrafluoroethylene are a significant source of thromboembolismhave poor durability due to neointimal hyperplasiaare susceptible to infectionand perhaps most importantly lack growth capacitywhich results in the need for additional operations as children outgrow their prostheticsThe development of better biomaterials with growth potential could substantially improve the outcomes of children requiring congenital heart surgery by reducing the number of graft related complications and enabling earlier definitive surgical repair without risk of serial re operationsTissue engineering offers a potential solution to this vexing problemUsing tissue engineering methodsbioprosthetics can be made from an individual s own cells creating a living material with excellent biocompatibility and the ability to growrepairand remodelThe goal of this application is to optimize the design of an improved vascular graft for use in congenital heart surgeryUsing the tissue engineered vascular graftTEVGas a model for bioprosthetics specifically developed for use in congenital heart surgerywe will rationally design an improved TEVG based on the mechanisms underlying vascular neotissue formationWe will focus our work on developing strategies for inhibiting TEVG stenosis by anti LYST immunomodulationThe successful development of therapeutic strategies for inhibiting TEVG stenosis would overcome a critical barrier preventing the widespread use of this promising technology Public Health Relevance Statement Congenital cardiac anomalies are the most common birth defect and a leading cause of death in the newborn periodThe most effective treatment for congenital cardiac anomalies is reconstructive surgeryUnfortunatelycomplications arising from the use of currently available vascular conduits are a significant cause of postoperative morbidity and mortalityThe development and translation of an improved vascular graftcreated from an individual s own cellswith the ability to grow and remodelholds great promise for advancing the field of congenital heart surgery and improving outcomes of infants requiring surgical intervention