Development of a novel organ culture system allowing independent control of local mechanical variables and its implementation in studying the effects of axial stress on arterial remodeling
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Arterial remodeling is a process by which arteries respond to sustained changes in their mechanical environment. This process occurs in a way such that an artery's local mechanical environment (circumferential, shear, and axial stress) is maintained at a homeostatic level. However, most studies utilize a methodology that controls the global parameters (pressure, flow rate, and axial stretch). This approach often confounds the results since the actual drivers of remodeling are not independently isolated. This research involved developing a methodology and system capable of independently controlling each of the local parameters and examining the effect of axial stress on remodeling. An organ culture system capable of monitoring and controlling the three global parameters and calculating the cross sectional geometry was developed. This combination of hardware was incorporated into LabVIEW which afforded the user the ability to define desired values for the local mechanical parameters. Porcine common carotid arteries were cultured for seven days in this system under physiologically normal circumferential and shear stresses and a constant axial stress of either 150 kPa or 300 kPa. Material response, general arterial morphology, tissue viability, and collagen synthesis were examined in order to gauge the effectiveness of the organ culture system and assess any arterial remodeling. The results of this study demonstrate the ability of the organ culture system in achieving and maintaining target values of stress throughout the culture period. Cell viability, general arterial morphology, and collagen synthesis rates were maintained for all arteries. The elevated axial stress appeared to cause a softening of the artery in both the axial and circumferential direction. It was hypothesized that this softening was the result of a changing collagen structure. Additional softening seen in arteries was attributed to the effects of the culture system.