Abstract Cyclic strain is known to influence many aspects of vascular cell biology (Mills et al., 1993). Certain vessels undergo some combination of cyclic distension, longitudinal stretching, and twist. In the coronary arteries, for example, the beating heart induces such motion (Pao et al., 1992; Hamid et al., 1992). Saphenous vein coronary bypass grafts endure similar deformations. It is thought that subjecting constituent cells to such strains contributes to the etiology and pathogenesis of certain vascular maladies. The in-vitro simulation of the cyclic strain associated with the vasculature has been carried out mostly by manipulating flat membranes on which cell monolayers are cultured (Mills et al., 1993). However, native vascular cells are subjected simultaneously to multidirectional forces and deformations in-situ, and this is not accurately simulated with existing devices. The purpose of this work was to create an apparatus which may be used to apply cyclic twist and longitudinal stretch consistent with those found in native blood vessels to perfused, intact, vascular specimens.
One of the major failings in vascular tissue engineering is the limited capacity of autologous differentiated cells to reconstitute tissues. A logical solution is the use of pluripotent stem cells, whose use in vascular treatments is yet to be fully realized. Although biochemical stimulation has been explored to differentiate bone marrow derived mesenchymal stem cells MeSCs to smooth muscle, the use of biomechanical forces in differentiation remains largely unexplored. We have begun preliminary investigations into the role of physiological levels of cyclic strain on MeSCs differentiation. Populations of cells were isolated from rat bone marrow by their adherence to tissue culture plastic. After 14 days in culture, the cells grew in colonies and the cells labelled positive for CD34, CD90 and CD117. Cells were cultured at sub-confluent levels and stimulated with 10% strain at 1 Hz for 7 days. Observations showed that cyclic strain inhibited proliferation and aligned the cells perpendicular to the direction of strain. In addition, cyclic stretch switched on vascular smooth muscle actin and h-calponin. These preliminary studies demonstrate the potential of physiologic biomechanical stimulation in the differentiation of MeSCs to cells of the vascular lineage, and this could have important implications for vascular tissue engineering.
Abstract Abdominal aortic aneurysm (AAA) is an irreversible focal dilation of the infrarenal aorta. If left untreated, AAA will continue to expand and eventually rupture. Ruptured AAA is ranked as the 13th leading cause of death in the United States [1]. Accurate prediction of AAA rupture is critical for patient management. From a biomechanical point of view, this occurs when the stress in the aneurysm wall exceeds its strength. Therefore, reliable assessment of the risk of AAA rupture demands information on wall stress as well as wall strength.
Vascular bypass graft failure is a significant clinical problem and is frequently due to the formation of intimal hyperplasia (IH) [1–3]. IH is characterized by the accumulation of smooth muscle cells (SMC) and extracellular matrix in the intima of the vessel, which occurs when the normal balance between vascular cell proliferation and apoptosis (regulated cell death) is altered [4]. The disturbed flow present at the anastomosis has been implicated in the formation of IH and the link between hemodynamics and graft failure is via a complex cascade of events whereby biomechanical forces cause biological responses [5, 6]. For example, immediate early genes (IEG) such as c-fos, c-jun and egr-1 are involved in the signaling pathways for proliferation and apoptosis. When extracellular biomechanical stimuli (e.g. shear stress) cause the expression of IEG, their protein products translocate to the nucleus. These proteins regulate the expression of a number of genes implicated in cardiovascular disease including growth factors, adhesion molecules, proapoptotic substrates and coagulation factors [7–9]. Because IEG are involved in both proliferation and apoptosis, their expression may upset the normal balance between cell proliferation and apoptosis and could play a vital role in the IH formation in vascular bypass grafts.
Rupture of abdominal aortic aneurysm (AAA) represents a significant clinical event, having a mortality rate of 90% and being currently ranked as the 13th leading cause of death in the US. The ability to reliably evaluate the susceptibility of a particular AAA to rupture on a case-specific basis could vastly improve the clinical management of these patients. Because AAA rupture represents a mechanical failure of the degenerated aortic wall, biomechanical considerations are important to understand this process and to improve our predictions of its occurrence. Presented here is an overview of research to date related to the biomechanics of AAA rupture. This includes a summary of results related to ex vivo and in vivo mechanical testing, noninvasive AAA wall stress estimations, and potential mechanisms of AAA wall weakening. We conclude with a demonstration of a biomechanics-based approach to predicting AAA rupture on a patient-specific basis, which may ultimately prove to be superior to the widely and currently used maximum diameter criterion.
