A Study Evaluating the Safety and Efficacy of Second-Generation Tissue Engineered Vascular Grafts (TEVG2)

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PROJECT SUMMARY We developed a tissue engineered vascular graft (TEVG) designed specifically for use in congenital heart surgery. The TEVG is made by seeding autologous bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold. Once implanted the scaffold degrades and the TEVG transforms into a neovessel that resembles a native blood vessel both in structure and function. Results of the first FDA- approved clinical trial evaluating the use of the TEVG in children demonstrated that the TEVG is the first man- made vascular conduit that grows making it uniquely suited for use in the surgical repair of complex congenital heart defects, however; results of this study also demonstrated that incidence of stenosis was too high to recommend routine use of this promising technology. We subsequently developed an improved, second- generation TEVG that incorporates both rationally designed strategies for inhibiting the formation of TEVG stenosis and process improvement measures for assembling the TEVG, in addition to newer less stringent criteria for performing TEVG angioplasty. Herein we propose the next step in the development and translation of the TEVG: a single-institution, prospective, single-armed, exploratory-confirmatory clinical trial designed to evaluate the safety and efficacy of the second-generation TEVG in 24 patients over a 2-year period. In this study, we will evaluate the short-term (2 year) safety and efficacy of a second-generation TEVG for use as an extracardiac conduit in children with single ventricle cardiac anomalies undergoing modified Fontan surgery. We will serially monitor all graft recipients over a 2-year time course using echocardiography and MRI. We hypothesize that the second-generation TEVG will have a significantly lower incidence of critical stenosis compared to the results of original TEVG in our previous FDA-approved pilot study. In addition, we hypothesize that the TEVG will grow and transform over time into a highly compliant capacitance vessel. We will evaluate the effect of graft compliance on flow, turbulence, and power loss across the TEVG in the Fontan circulation. The development of a man-made vascular graft with growth capacity would enable the performance of definitive reconstructive surgical procedures at an early age and mitigate the need for additional surgeries due to somatic overgrowth (the process by which a child outgrows their implant), thereby improving outcomes in patients with congenital heart disease.