Pulsatile Perfusion Bioreactor for Biomimetic Vascular Impedances

Abstract

Pulsatile waves of blood pressure and flow are continuously augmented by the resistance, compliance, and inertance properties of the vasculature, resulting in unique wave characteristics at distinct anatomical locations. Hemodynamically generated loads, transduced as physical signals into resident vascular cells, are crucial to the maintenance and preservation of a healthy vascular physiology; thus, failure to recreate biomimetic loading in vitro can lead to pathological gene expression and aberrant remodeling. As a generalized approach to improve native and engineered blood vessels, we have designed, built, and tested a pulsatile perfusion bioreactor based on biomimetic impedances and a novel five-element electrohydraulic analog. Here, the elements of an incubator-based culture system were formulaically designed to match the vascular impedance of a brachial artery by incorporating both the inherent (systemic) and added elements of the physical system into the theoretical approach. Freshly harvested porcine saphenous veins were perfused within a physiological culture chamber for 6 h and the relative expression of seven known mechanically sensitive remodeling genes analyzed using the quantitative polymerase chain reaction (qPCR) method. Of these, we found plasminogen activator inhibitor-1 (SERPINE1) and fibronectin-1 (FN1) to be highly sensitive to differences between arterial- and venous-like culture conditions. The analytical approach and biological confirmation provide a framework toward the general design of long-term hemodynamic-mimetic vascular culture systems.