Computational Optimization of Compliance Matched Tissue Engineered Vascular Grafts

Abstract

Coronary heart disease is a leading cause of death among Americans for which coronary artery bypass graft (CABG) surgery is a standard surgical treatment. The success of CABG surgery is impaired by the compliance mismatch between vascular grafts and native vessels. Tissue engineered vascular grafts (TEVGs) have the potential to be compliance matched and thereby reduce the risk of graft failure. Glutaraldehyde (GLUT) vapor-crosslinked gelatin/fibrinogen constructs were fabricated and mechanically tested in a previous study by our research group at 2, 8, and 24 hours of GLUT vapor exposure. Constructs electrospun with tropoelastin in addition to gelatin and fibrinogen fibers were also fabricated and tested for the same amounts of GLUT vapor exposure. The current study details a computational method that was developed to predict the material properties of our constructs for crosslinking times between 2 and 24 hours by interpolation and regression of the 2, 8, and 24 hour crosslinking time data. Matlab and Abaqus were used to determine the optimal combination of fabrication parameters to produce compliance matched constructs. The validity of the method was first tested on a 16 hour crosslinked gelatin/fibrinogen construct of 130μm thickness. The predicted compliance was 0.00059 mmHg-1 while the experimentally determined compliance was 0.00065 mmHg-1, a relative difference of 9.2%. Prior data in our laboratory has shown the compliance of the left anterior descending porcine coronary (LADC) artery to be 0.00071 ± 0.0003 mmHg-1. The optimization algorithm predicts that a 258μm thick construct that is GLUT vapor crosslinked for 8.1 hours would match LADC compliance. The algorithm was expanded to predict the compliance of constructs consisting of alternating layers of tropoelastin/gelatin/fibrinogen and gelatin/fibrinogen. A four layered graft was designed and fabricated using this optimization routine. The layered construct was found to have a compliance of 0.00051 mmHg-1 while the predicted compliance was 0.00061 mmHg-1, a difference of 16%. This is a promising method for matching the compliance of our TEVGs with the native tissue of various specimens.