A Novel Pulse Damper for Endothelial Cell Flow Bioreactors.

PURPOSE: Peristaltic pumps (PP) are favored in flow bioreactors for their non-contact sterile design. But they produce pulsatile flow, which is consequential for the cultured cells. A novel pulse damper (PD) is reported for pulsatility elimination. METHODS: The PD design was implemented to target static pressure pulsatility and flow rate (velocity) pulsatility from a PP. Damping effectiveness was tested in a macro-scale, closed-loop recirculating bioreactor mimicking the aortic arch at flow rates up to (4 L/min). Time-resolved particle image velocimetry was used to characterize the velocity field. Endothelial cells (EC) were grown in the bioreactor, and subjected to continuous flow for 15 min with or without PD. RESULTS: The PD was found to be nearly 90% effective at reducing pulsatility. The EC exposed to low PP flow without PD exhibited distress signaling in the form of increased ERK1/2 phosphorylation (2.5 folds) when compared to those exposed to the same flow with PD. At high pump flow without PD, the cells detached and did not survive, while they were perfectly healthy with PD. CONCLUSIONS: Flow pulsatility from PP causes EC distress at low flow and cell detachment at high flow. Elevated temporal shear stress gradient combined with elevated shear stress magnitude at high flow are believed to be the cause of cell detachment and death. The proposed PD design was effective at minimizing the hemodynamic stressors in the pump's output, demonstrably reducing cell distress. Adoption of the proposed PD design in flow bioreactors should improve experimental protocols.

Distribution of hepatic venous blood in the total cavo pulmonary connection: an in vitro study into the effects of connection geometry.

The total cavo pulmonary connection, or TCPC, is a surgical correction to congenital heart defects. The geometry of this connection has been shown to determine the fluid power loss as well as the distribution of hepatic fluid that enters through the inferior vena cava. In vitro studies were performed to measure the power loss and hepatic fluid distribution in models of the TCPC with four different geometries. It was found that a zero offset straight geometry provided good hepatic fluid distribution but large power loss. A zero offset flared geometry provided low power loss but poor hepatic fluid distribution. The optimal geometry from those tested was found to be the zero offset cowl geometry whereby an enlargement was made on one side of the inferior and superior vena cava. So long as the cowl was directed toward the pulmonary artery of lowest flow rate, low power loss and relatively good distribution of hepatic flow could be obtained.