Elucidating the role of graft compliance mismatch on intimal hyperplasia using an ex vivo organ culture model

Abstract

There is a growing clinical need to address high failure rates of small diameter (<6 mm) synthetic vascular grafts. Although there is a strong empirical correlation between low patency rates and low compliance of synthetic grafts, the mechanism by which compliance mismatch leads to intimal hyperplasia is poorly understood. To elucidate this relationship, synthetic vascular grafts were fabricated that varied compliance independent of other graft variables. A computational model was then used to estimate changes in fluid flow and wall shear stress as a function of graft compliance. The effect of compliance on arterial remodeling in an ex vivo organ culture model was then examined to identify early markers of intimal hyperplasia. The computational model prediction of low wall shear stress of low compliance grafts and clinical control correlated well with alterations in arterial smooth muscle cell marker, extracellular matrix, and inflammatory marker staining patterns at the distal anastomoses. Conversely, high compliance grafts displayed minimal changes in fluid flow and arterial remodeling, similar to the sham control. Overall, this work supports the intrinsic link between compliance mismatch and intimal hyperplasia and highlights the utility of this ex vivo organ culture model for rapid screening of small diameter vascular grafts. STATEMENT OF SIGNIFICANCE: We present an ex vivo organ culture model as a means to screen vascular grafts for early markers of intimal hyperplasia, a leading cause of small diameter vascular graft failure. Furthermore, a computational model was used to predict the effect of graft compliance on wall shear stress and then correlate these values to changes in arterial remodeling in the organ culture model. Combined, the ex vivo bioreactor system and computational model provide insight into the mechanistic relationship between graft-arterial compliance mismatch and the onset of intimal hyperplasia.

Keywords: Bioreactor; Compliance; Computational model; Intimal hyperplasia; Vascular graft; Wall shear stress.