Comparison of the Long-Term Efficacy of Tissue-Engineered Vascular Grafts Versus Polytetrafluoroethylene Conduits Using an Established Preclinical Model
Abstract
Topic Area: This study addresses the topic area of congenital heart disease and the area of emphasis focused on development of approaches, including regenerative medicine, that provide structural support, restore native activity, allow for tissue growth, and prevent the need for reoperation. Objective and Rationale for the Proposed Study: Congenital heart disease represents the most common birth defect. Severe forms of congenital heart disease are life-threatening and require surgical repair. While there has been significant progress made in the surgical care of patients born with congenital heart disease, it remains a leading cause of death in the newborn period. A significant source of complications after congenital heart surgery arises from the use of man-made biomaterials in the form of vascular patches, grafts, or replacement heart valves, which are required in most major congenital heart operations. One problem associated with the use of man-made materials is that they lack growth potential so a child can outgrow his or her operation and require additional operations, which can cause additional problems. Tissue engineering attempts to create tissues from an individual’s own cells. Tissues can be defined as groups of cells working together to perform a function (for example, blood vessel tissue is composed of endothelial cells, smooth muscle cells, and fibroblasts, which function together to ensure blood flow throughout the circulatory system). One method of tissue engineering uses a biodegradable, three-dimensional, scaffold or matrix upon which cells can be seeded. The scaffold provides sites for cell attachment and space for tissue formation. Over time, the scaffold degrades while the tissue forms, ultimately creating a living tissue without any man-made components. Furthermore, the scaffold can serve as a template to direct tissue formation. We have previously used tissue engineering methods to create a tissue engineered vascular graft (TEVG). We performed the first clinical trial evaluating the use TEVGs in congenital heart surgery and confirmed the growth potential of the TEVG in humans. This study demonstrated that the TEVG had a tendency to form stenosis (narrowing) in some patients. In our previous Technology/Therapeutic Development Award (TTDA), we developed an improved second-generation TEVG designed to prevent narrowing. Based in part on results if this study, we obtained U.S. Food and Drug Administration (FDA) approval and initiated a new clinical trial evaluating the safety of the second-generation TEVG. The proposed expansion award builds on our initial TTDA. In the proposed study, we will evaluate the late-term performance of the second-generation TEVGs compared to the current standard of care (PTFE grafts). We will use an established large animal model to measure the structural and functional characteristics of conduit that affect its performance and determine its efficacy. We have two cohorts of sheep that were previously implanted with either TEVGs or PTFE grafts beginning in 2016 and have been serially monitored with various imaging modalities. During the course of the proposed investigation, since the average lifespan of sheep is approximately 10 years, we would be able to evaluate the performance of the grafts over the natural lifespan of these animals. Successful completion of this project coupled with successful completion of our clinical study would provide the data necessary for obtaining FDA approval. Central Problem to be Addressed: Currently used vascular grafts lack growth capacity. Therefore, patients undergoing congenital heart surgery have the potential to outgrow their operations and require additional procedures, which put them at risk for additional complications. We previously developed tissue engineered vascular patches, grafts, and replacement heart valves with growth capacity, and in a clinical pilot study evaluating the TEVG in congenital heart surgery, we confirmed i
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210597
Entities
People
- Christopher K. Breuer
Organizations
- United States Army