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A Novel Pulse Damper for Endothelial Cell Flow Bioreactors

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Abstract

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.

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Abbreviations

CCD:

Charge coupled device

EC:

Endothelial cells

ERK:

Extra-cellular signal-regulated kinase

fps:

Frames per second

HUVEC:

Human umbilical vein endothelial cells

ID:

Inner diameter

MAP:

Mitogen activated protein

OD:

Outer diameter

OSI:

Oscillatory shear stress

PD:

Pulse damper

PDMS:

Polydimethylsiloxane

PIV:

Particle image velocimetry

PP:

Peristaltic pump

psig:

Pound per square inch, gauge

RPM:

Revolution per minute

\(f\) :

Flow signal (pressure, flow rate, or shear stress)

\(\varvec{p}\) :

Static pressure

\(\varvec{q}\) :

Flow rate

\(\varvec{u}\left( \varvec{y} \right)\) :

Flow velocity distribution near the vessel wall

\(y\) :

Perpendicular distance from the vessel wall

\(\mu\) :

Dynamic viscosity

\(\varvec{\tau}_{\varvec{w}}\) :

Wall shear stress

\(\varvec{\psi}\) :

Damping effectiveness based on signal standard deviation

\(\phi\) :

Damping effectiveness based on signal peak-to-peak

\({\mathbf{K}}\) :

Peak-to-peak of a waveform or signal

\({\varvec{\upsigma}}\) :

Standard deviation of a waveform or signal

\(\varvec{D}\) :

Damped

\(\varvec{U}\) :

Un-damped

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Acknowledgments

Casting molds for the arched bioreactor model were produced via CNC machining by J. Nassif and J. Zoullikian. GFO thanks Prof. SL Ceccio from U. Michigan for hosting his sabbatical which made the production of this manuscript possible.

Funding

This work was supported by the American University of Beirut through the Faculty of Engineering and Architecture (Dar-Shair Grant), and the Faculty of Medicine (F. Jabre Grant).

Conflict of interest

M.M. Alloush declares that he has no conflict of interest. M. Liermann declares that he has no conflict of interest. A Zedan declares that he has no conflict of interest. G.F. Oweis declares that he has no conflict of interest.

Ethical Approval

No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article. The HUVEC culture used in this study was obtained commercially.

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Author notes

  1. M. Liermann

    Present address: Danfoss Power Solutions, Krokamp 35, 24539, Neumünster, Germany

Authors and Affiliations

  1. Department of Mechanical Engineering, MS Faculty of Engineering and Architecture, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon

    M. M. Alloush, M. Liermann & G. F. Oweis

  2. Department of Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon

    A. Zedan

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  1. M. M. Alloush
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Correspondence to G. F. Oweis.

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Associate Editor Jonathan Butcher and Ajit P. Yoganathan oversaw the review of this article.

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Alloush, M.M., Liermann, M., Zedan, A. et al. A Novel Pulse Damper for Endothelial Cell Flow Bioreactors. Cardiovasc Eng Tech 10, 95–111 (2019). https://doi.org/10.1007/s13239-018-00394-y

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