Biomechanical Comparison of Glutaraldehyde-Crosslinked Gelatin Fibrinogen Electrospun Scaffolds to Porcine Coronary Arteries

Abstract

Cardiovascular disease (CVD) is the leading cause of death for Americans. As coronary artery bypass graft surgery (CABG) remains a mainstay of therapy for CVD and native vein grafts are limited by issues of supply and lifespan, an effective readily available tissue-engineered vascular graft (TEVG) for use in CABG would provide drastic improvements in patient care. Biomechanical mismatch between vascular grafts and native vasculature has been shown to be the major cause of graft failure, and therefore, there is need for compliance-matched biocompatible TEVGs for clinical implantation. The current study investigates the biaxial mechanical characterization of acellular electrospun glutaraldehyde (GLUT) vapor-crosslinked gelatin/fibrinogen cylindrical constructs, using a custom-made microbiaxial optomechanical device (MOD). Constructs crosslinked for 2, 8, and 24 hrs are compared to mechanically characterized porcine left anterior descending coronary (LADC) artery. The mechanical response data were used for constitutive modeling using a modified Fung strain energy equation. The results showed that constructs crosslinked for 2 and 8 hrs exhibited circumferential and axial tangential moduli (ATM) similar to that of the LADC. Furthermore, the 8-hrs experimental group was the only one to compliance-match the LADC, with compliance values of 0.0006±0.00018 mm Hg-1 and 0.00071±0.00027 mm Hg-1, respectively. The results of this study show the feasibility of meeting mechanical specifications expected of native arteries through manipulating GLUT vapor crosslinking time. The comprehensive mechanical characterization of cylindrical biopolymer constructs in this study is an important first step to successfully develop a biopolymer compliance-matched TEVG.

Computationally Optimizing the Compliance of a Biopolymer Based Tissue Engineered Vascular Graft

“…TEVGs are a potential solution to the aforementioned issues associated with bypass graft surgery as they can be engineered to have a compliance that matches that of the native vessel and also to be nonthrombogenic, biocompatible, nonimmunogenic, and infection resistant [4]. In order to design a compliance-matched TEVG, it is a logical first step to try to mimic the material and microstructure of a native vessel.…”

“…Our research group has successfully electrospun and characterized nonsynthetic biopolymer vascular grafts using gelatin and fibrinogen. The effect of crosslinking time via exposure to GLUT vapor on their mechanical behavior was also characterized [4]. Because compliance matching with the host artery is of critical importance in graft design [2,3,8], a computational technique has been developed to predict the compliance of our constructs based on the thickness of the construct and the duration of crosslinking time.…”

“…These constructs were then removed from the stainless steel rod and suspended in the air in a chamber containing 25% (v/v) liquid GLUT. Three experimental groups with three replicates each were created and allowed to crosslink for 2, 8, and 24 hrs before mechanical testing [4]. These constructs were used as the basis for the present study.…”

“…Six different protocols were performed on each specimen. After preconditioning, the intraluminal pressure was increased from 0 to 120 mm Hg with constant axial loads of 0, 10, and 30 g. The axial load was then increased from 0 to 30 g with constant intraluminal pressures of 0, 70, and 120 mm Hg [4,15,16].…”

“…50 mm Hg (1) where D 120 and D 70 are the diameters of the construct at an intraluminal pressure of 120 mm Hg and 70 mm Hg, respectively. Data from the mechanical testing were fit to a four-parameter Fung-type strain energy model [4,15]…”