A bioengineering approach aimed at understanding the role of hemodynamic forces acting on human saphenous vein after coronary artery by-pass grafting

Saphenous vein (SV) graft disease represents an unresolved problem in coronary artery bypass grafting (CABG). After CABG, a progressive remodeling of the SV wall occurs, possibly leading to the lumen occlusion. This process is termed intima hyperplasia (IH). The investigation of cellular and molecular aspects of IH progression is a primary endpoint toward the generation of occlusion-free vessels that may be used as ‘life-long’ grafts. While animal transplantation and in vitro models have clarified some of the remodeling factors, the human SV pathology is far from being completely understood. The aim of the present doctoral project was to explore new tools and procedures to investigate ex vivo the effects of altered mechanical load experienced by the human SV after CABG surgery. The issue of the ex vivo mimicry of the pathologic arterialization mechanism, involved in SV graft disease, was addressed by a multidisciplinary approach. Advanced bioengineering/biotechnology modeling and prototyping tools, complying with biological methods and tissue engineering/regenerative medicine requirements, were applied. Furthermore, the application of principles and methods of life-science engineering were used for providing a reliable model system, facilitating the understanding of pathogenesis of vein graft IH. Particular focus was given to the control over the environmental conditions for tightly reproducing the essential stimuli involved in the pathological SV remodelling. The integration of these methodologies led to devising a novel laboratory-oriented culture platform, that was used for conducting extensive arterialization conditioning campaigns with human SVs, under strictly controlled hemodynamic conditions. The resulting ex vivo platform tried to overcome some of the limitations of the state-of-the-art models, focusing onto the control of the hemodynamic and biochemical microenvironments. In our view, this is crucial to obtain a global comprehension of VGD progression, and in perspective to perform comparative studies of drug administration or gene expression modulation (gene therapy, siRNA and antagomir approaches), to devise preconditioning protocols and/or regenerative medicine strategies that reduce the clinical impact of VGD pathology.