Development and Preclinical Validation of an Improved Tissue-Engineered Vascular Graft for Use in Congenital Heart Surgery
Abstract
Topic Area: This study addresses the FY16 PRMRP topic area Congenital Heart Disease and the area of emphasis focused on research on tissue engineering approaches to patches, grafts, and transplantation that provide structural support, restore native activity, allow for tissue growth, and prevent the need for reoperation. Comprehensive Overview of the Proposed Project: Congenital cardiac anomalies represent the most common form of 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 is the use of manmade biomaterials in the form of vascular patches, grafts, or replacement heart valves, which are used in most major congenital heart operations. One problem associated with the use of manmade 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, heart valve tissue is composed of endothelial cells and valvular interstitial cells, which function together to ensure unidirectional blood flow). One method of tissue engineering uses a biodegradable (dissolvable) three-dimensional scaffold 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 manmade components. Furthermore, the scaffold can serve as a template to direct tissue formation. We have previously used tissue engineering methods to create tissue-engineered vascular patches, grafts, and replacement heart valves and demonstrated the growth capacity of these living structures using animal models. We also performed the first clinical trial evaluating the use of tissue-engineered vascular grafts (TEVGs) in congenital heart surgery and confirmed the growth capacity of the TEVG in humans. This study also demonstrated that the TEVG had a tendency to form stenosis (narrowing) in some patients. This narrowing was problematic for it decreased blood flow and in severe cases required an additional procedure (angioplasty) to be performed to dilate the narrowing, open up the blood vessel, and restore flow. In order to improve the design of the TEVG, we investigated the cause of TEVG stenosis and then, based on our discoveries, redesigned the TEVG to prevent the formation of TEVG stenosis. In this study, we propose using a large animal model to investigate and compare the performance of second generation TEVGs, designed to inhibit the formation of stenosis, to polytetrafluoroethylene (PTFE) grafts, the most commonly used vascular grafts in congenital heart surgery. In the first part of the study, we will evaluate the safety and growth capacity of TEVGs made using several different cell doses compared to PTFE vascular grafts. In the second part of the study, we will use these data to develop a computational model that describes changes in graft structure and could be useful for predicting graft performance. In the final portion of the investigation, we will evaluate the predictive capability of the computational model and use it to further optimize the design and use of the TEVG. Central Problem To Be Addressed: Currently used vascular patches, grafts, and replacement heart valves 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
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810518
Entities
People
- Christopher K. Breuer
Organizations
- United States Army