Abstract

Extracorporeal membrane oxygenation (ECMO) has been used clinically for more than 40 years as a bridge to transplantation, with hollow-fiber membrane (HFM) oxygenators gaining in popularity due to their high gas transfer and low flow resistance. In spite of the technological advances in ECMO devices, the inevitable contact of the perfused blood with the polymer hollow-fiber gas-exchange membrane, and the subsequent thrombus formation, limits their clinical usage to only 2–4 weeks. In addition, the inhomogeneous flow in the device can further enhance thrombus formation and limit gas-transport efficiency. Endothelialization of the blood contacting surfaces of ECMO devices offers a potential solution to their inherent thrombogenicity. However, abnormal shear stresses and inhomogeneous blood flow might affect the function and activation status of the seeded endothelial cells (ECs). In this study, the blood flow through two HFM oxygenators, including the commercially available iLA® MiniLung Petite Novalung (Xenios AG, Germany) and an experimental one for the rat animal model, was modeled using computational fluid dynamics (CFD), with a view to assessing the magnitude and distribution of the wall shear stress (WSS) on the hollow fibers and flow fields in the oxygenators. This work demonstrated significant inhomogeneity in the flow dynamics of both oxygenators, with regions of high hollow-fiber WSS and regions of stagnant flow, implying a variable flow-induced stimulation on seeded ECs and possible EC activation and damage in a biohybrid oxygenator setting.

References

1.
WHO
,
2016
, “Top 10 Global Causes of Death,” World Health Organization, Geneva, Switzerland, accessed Dec. 11, 2020, http://www.who.int/mediacentre/factsheets/fs310/en/
2.
Kozower
,
B. D.
,
Meyers
,
B. F.
,
Smith
,
M. A.
,
De Oliveira
,
N. C.
,
Cassivi
,
S. D.
,
Guthrie
,
T. J.
,
Wang
,
H.
,
Ryan
,
B. J.
,
Shen
,
K. R.
,
Daniel
,
T. M.
, and
Jones
,
D. R.
,
2008
, “
The Impact of the Lung Allocation Score on Short-Term Transplantation Outcomes: A Multicenter Study
,”
J. Thorac. Cardiovasc. Surg.
,
135
(
1
), pp.
166
171
.10.1016/j.jtcvs.2007.08.044
3.
Bartlett
,
R. H.
,
2005
, “
Extracorporeal Life Support: History & Directions
,”
Semin. Perinatol.
,
29
(
1
), pp.
2
7
.10.1053/j.semperi.2005.02.002
4.
Madhani
,
S. P.
,
D'Aloiso
,
B. D.
,
Frankowski
,
B.
, and
Federspiel
,
W. J.
,
2016
, “
Darcy Permeability of Hollow Fiber Membrane Bundles Made From Membrana Pmp Fibers Used in Respiratory Assist Devices
,”
ASAIO J
,
62
(
3
), pp.
329
331
.10.1097/MAT.0000000000000348
5.
Haft
,
J. W.
,
Griffith
,
B. P.
,
Hirschl
,
R. B.
, and
Bartlett
,
R. H.
,
2002
, “
Results of an Artificial-Lung Survey to Lung Transplant Program Directors
,”
J. Heart Lung Transplant.
,
21
(
4
), pp.
467
473
.10.1016/S1053-2498(01)00378-3
6.
Wu
,
Z. J.
,
Taskin
,
M. E.
,
Zhang
,
T.
,
Fraser
,
K. H.
, and
Griffith
,
B. P.
,
2012
, “
Computational Model-Based Design of a Wearable Artificial Pump-Lung for Cardiopulmonary/Respiratory Support
,”
J. Artif. Organs
,
36
(
4
), pp.
387
399
.10.1111/j.1525-1594.2011.01369.x
7.
Zhang
,
J.
,
Taskin
,
M. E.
,
Koert
,
A.
,
Zhang
,
T.
,
Gellman
,
B.
,
Dasse
,
K. A.
,
Gilbert
,
R. J.
,
Griffith
,
B. P.
, and
Wu
,
Z. J.
,
2009
, “
Computational Design and In Vitro Characterization of an Integrated Maglev Pump-Oxygenator
,”
J. Artif. Organs
,
33
(
10
), pp.
805
817
.10.1111/j.1525-1594.2009.00807.x
8.
Fischer
,
S.
,
Simon
,
A. R.
,
Welte
,
T.
,
Hoeper
,
M. M.
,
Meyer
,
A.
,
Tessmann
,
R.
,
Gohrbandt
,
B.
,
Gottlieb
,
J.
,
Haverich
,
A.
, and
Strueber
,
M.
,
2006
, “
Bridge to Lung Transplantation With the Novel Pumpless Interventional Lung Assist Device NovaLung
,”
J. Thorac. Cardiovasc. Surg.
,
131
(
3
), pp.
719
723
.10.1016/j.jtcvs.2005.10.050
9.
Conrad
,
S.
,
Zwischenberger
,
J. B.
,
Eggerstedt
,
J. M.
, and
Bidani
,
A.
,
1994
, “
In V3ivo Gas Transfer Performance of the Intravascular Oxygenator in Acute Respiratory Failure
,”
J. Artif. Organs
,
18
(
11
), pp.
840
845
.10.1111/j.1525-1594.1994.tb03333.x
10.
Gartner
,
M. J.
,
Wilhelm
,
C. R.
,
Gage
,
K. L.
,
Fabrizio
,
M. C.
, and
Wagner
,
W. R.
,
2000
, “
Modeling Flow Effects on Thrombotic Deposition in a Membrane Oxygenator
,”
J. Artif. Organs
,
24
(
1
), pp.
29
36
.10.1046/j.1525-1594.2000.06384.x
11.
Haines
,
N. M.
,
Rycus
,
P. T.
,
Zwischenberger
,
J. B.
,
Bartlett
,
R. H.
, and
Undar
,
A.
,
2009
, “
Extracorporeal Life Support Registry Report 2008: Neonatal and Pediatric Cardiac Cases
,”
ASAIO J
,
55
(
1
), pp.
111
116
.10.1097/MAT.0b013e318190b6f7
12.
Lemon
,
G.
,
Lim
,
M. L.
,
Ajalloueian
,
F.
, and
Macchiarini
,
P.
,
2014
, “
The Development of the Bioartificial Lung
,”
Br. Med. Bull.
,
110
(
1
), pp.
35
45
.10.1093/bmb/ldt037
13.
Bhavsar
,
S. S.
,
Schmitz-Rode
,
T.
, and
Steinseifer
,
U.
,
2011
, “
Numerical Modeling of Anisotropic Fiber Bundle Behavior in Oxygenators
,”
J. Artif. Organs
,
35
(
11
), pp.
1095
1102
.10.1111/j.1525-1594.2011.01365.x
14.
Pantalos
,
G.
,
2009
, “
Use of Computer and In Vitro Modeling Techniques During the Development of Pediatric Circulatory Support Devices
,”
ASAIO J
,
55
(
1
), pp.
3
5
.10.1097/MAT.0b013e318198dd88
15.
Taskin
,
M. E.
,
Fraser
,
K. H.
,
Zhang
,
T.
,
Griffith
,
B. P.
, and
Wu
,
Z. J.
,
2010
, “
Micro-Scale Modeling of Flow and Oxygen Transfer in Hollow Fiber Membrane Bundle
,”
J. Membr. Sci.
,
362
(
1–2
), pp.
172
183
.10.1016/j.memsci.2010.06.034
16.
Darby
,
R.
,
2001
,
Chemical Engineering Fluid Mechanics
, 2nd ed.,
Marcel Dekker
,
New York
.
17.
Malek
,
A.
,
Li
,
K.
, and
Teo
,
W. K.
,
1997
, “
Modeling of Microporous Hollow Fiber Membrane Modules Operated Under Partially Wetted Conditions
,”
Ind. Eng. Chem. Res.
,
36
(
3
), pp.
784
793
.10.1021/ie960529y
18.
Zierenberg
,
J. R.
,
Fujioka
,
H.
,
Hirschl
,
R. B.
,
Bartlett
,
R. H.
, and
Grotberg
,
J. B.
,
2007
, “
Pulsatile Blood Flow and Oxygen Transport Past a Circular Cylinder
,”
ASME J. Biomech. Eng.
,
129
(
2
), pp.
202
215
.10.1115/1.2485961
19.
Dierickx
,
P. W.
,
de Wachter
,
D. S.
, and
Verdonck
,
P. R.
,
2001
, “
2D Finite Element Model for Oxygen Transfer in Cross-Flow Hollow Fiber Membrane Artificial Lung
,”
Int. J. Artif. Organs
,
24
(
9
), pp.
628
635
.10.1177/039139880102400904
20.
Zhang
,
J.
,
Zhang
,
T.
,
Nolan
,
T. D. C.
,
Griffith
,
B. P.
, and
Wu
,
Z. L.
,
2006
, “
Progress Toward a Multi-Objective Model for Artificial Lung Devices
,”
J. Biomech.
,
39
(
1
), p.
S255
.10.1016/S0021-9290(06)83970-9
21.
Chan
,
K. Y.
,
Fujioka
,
H.
,
Suresh
,
V.
,
Bartlett
,
R. H.
,
Hirschl
,
R. B.
, and
Grotberg
,
J. B.
,
2006
, “
Pulsatile Flow and Mass Transport Over an Array of Cylinders: Gas Transfer in a Cardiac-Driven Artificial Lung
,”
ASME J. Biomech. Eng.
,
128
(
1
), pp.
85
96
.10.1115/1.2133761
22.
Zierenberg
,
J. R.
,
Fujioka
,
H.
,
Cook
,
K.
, and
Grotberg
,
J. B.
,
2008
, “
Pulsatile Flow and Oxygen Transport Past Cylindrical Fiber Arrays for an Artificial Lung: Computational and Experimental Studies
,”
ASME J. Biomech. Eng.
,
130
(
3
), p.
031019
.10.1115/1.2907752
23.
Fung
,
Y. C.
,
1969
, “
Blood Flow in the Capillary Bed
,”
J. Biomech.
,
2
(4), pp. 353–372.10.1016/0021-9290(69)90013-X
24.
Esch
,
M. B.
,
Post
,
D. J.
,
Shuler
,
M. L.
, and
Stokol
,
T.
,
2011
, “
Characterization of In Vitro Endothelial Linings Grown Within Microfluidic Channels
,”
Tissue Eng., Part A
,
17
(
23–24
), pp.
2965
2971
.10.1089/ten.tea.2010.0371
25.
Ergun
,
S.
,
1952
, “
Fluid Flow Through Packed Columns
,”
Chem. Eng. Prog.
,
48
(
2
), pp.
89
94
.http://dns2.asia.edu.tw/~ysho/YSHO-English/2000%20Engineering/PDF/Che%20Eng%20Pro48,%2089.pdf
26.
Milnor
,
W.
,
1982
,
Haemodynamics
,
Williams & Wilkins
,
Baltimore, MD
, p.
390
.
27.
Prasad
,
R. M.
,
Jin
,
X.
,
Aboualaiwi
,
W. A.
, and
Nauli
,
S. M.
,
2014
, “
Real-Time Vascular Mechanosensation Through Ex Vivo Artery Perfusion
,”
Biol. Proced. Online
,
16
(
1
), p.
6
.10.1186/1480-9222-16-6
28.
ANSYS, Inc.,
2018
, “
ANSYS Fluent 19.2. User's Guide
,” ANSYS Inc., Canonsburg, PA.
29.
Gage
,
K. L.
,
Gartner
,
M. J.
,
Burgreen
,
G. W.
, and
Wagner
,
W. R.
,
2002
, “
Predicting Membrane Oxygenator Pressure Drop Using Computational Fluid Dynamics
,”
Artif. Organs
,
26
(
7
), pp.
600
607
.10.1046/j.1525-1594.2002.07082.x
30.
Lipowsky
,
H. H.
,
Kovalcheck
,
S.
, and
Zweifach
,
B. W.
,
1978
, “
The Distribution of Blood Rheological Parameters in the Microvasculature of Cat Mesentery
,”
Circ. Res.
,
43
(
5
), pp.
738
749
.10.1161/01.RES.43.5.738
31.
Zarins
,
C. K.
,
Giddens
,
D. P.
,
Bharadvaj
,
B. K.
,
Sottiurai
,
V. S.
,
Mabon
,
R. F.
, and
Glagov
,
S.
,
1983
, “
Carotid Bifurcation Atherosclerosis: Quantitative Correlation of Plaque Localization With Flow Velocity Profiles and Wall Shear Stress
,”
Circ. Res.
,
53
(
4
), pp.
502
514
.10.1161/01.RES.53.4.502
32.
Marieb Elaine
,
N.
, and
Hoehn
,
K.
,
2013
, “
The Cardiovascular System: Blood Vessels
,”
Human Anatomy & Physiology
, 9th ed.,
Pearson Education
, Boston, MA, p.
712
.
33.
Aird
,
W. C.
,
2012
, “
Endothelial Cell Heterogeneity
,”
Cold Spring Harbor Perspect. Med.
,
2
(
1
), p.
a00642
.10.1101/cshperspect.a006429
34.
Nayak
,
A.
,
Konig
,
C. S.
,
Kishore
,
U.
, and
Evans
,
P. C.
,
2013
, “
Regulation of Endothelial Activation and Vascular Inflammation by Shear Stress
,”
Micro and Nano Flow Systems for Bioanalysis
,
M. W.
Collins
and
C. S.
Koenig
, eds.,
Springer
,
New York
, pp.
77
85
.
35.
Coenen
,
D. M.
,
Mastenbroek
,
T. G.
, and
Cosemans
,
J. M. E. M.
,
2017
, “
Platelet Interaction With Activated Endothelium: Mechanistic Insights From Microfluidics
,”
Blood
,
130
(
26
), pp.
2819
2828
.10.1182/blood-2017-04-780825
36.
Vercaemst
,
L.
,
2008
, “
Haemolysis in Cardiac Surgery Patients Undergoing Cardiopulmonary Bypass: A Review in Search of a Treatment Algorithm
,”
J. Extra Corpor. Technol.
,
40
(
4
), pp.
257
267
. https://pubmed.ncbi.nlm.nih.gov/19192755/
37.
Nolan
,
H.
,
Wang
,
D.
, and
Zwischenberger
,
J. B.
,
2011
, “
Artificial Lung Basics: Fundamental Challenges, Alternative Designs and Future Innovations
,”
Organogenesis.
,
7
(
1
), pp.
23
27
.10.4161/org.7.1.14025
38.
Hastings
,
S.
,
Ku
,
D.
,
Wagoner
,
S.
,
Maher
,
K.
, and
Deshpande
,
S.
,
2017
, “
Sources of Circuit Thrombosis in Pediatric Extra-Corporeal Membrane Oxygenation
,”
ASAIO J.
,
63
(
1
), pp.
86
92
.10.1097/MAT.0000000000000444
39.
Deshpande
,
S. R.
,
Hastings
,
S.
,
Wagoner
,
S.
,
Ku
,
D.
, and
Maher
,
K.
, April
2015
, “
New Insights Into Thrombosis in ECMO: Circuits: Where, How and Why?
,”
J. Heart Lung Transplant.
,
34
(4S), pp. S87–S88.10.1016/ j.healun.2015.01.232
40.
Zhang
,
J.
,
Nolan
,
T. D. C.
,
Zhang
,
T.
,
Griffith
,
B. P.
, and
Wu
,
Z. J.
,
2007
, “
Characterization of Membrane Blood Oxygenation Devices Using Computational Fluid Dynamics
,”
J. Membr. Sci.
,
288
(
1–2
), pp.
268
279
.10.1016/j.memsci.2006.11.041
41.
Goerke
,
A. R.
,
Leung
,
J.
, and
Wickramasinghe
,
S. R.
,
2002
, “
Mass and Momentum Transfer in Blood Oxygenators
,”
Chem. Eng. Sci.
,
57
(
11
), pp.
2035
2046
.10.1016/S0009-2509(02)00099-4
42.
Catapano
,
G.
,
Papenfuss
,
H. D.
,
Wodetzki
,
A.
, and
Baurmeister
,
U.
,
2001
, “
Mass & Momentum Transport in Extra-Luminal Flow Membrane Devices for Blood Oxygenation
,”
J. Membr. Sci.
,
184
, pp.
123
135
.10.1016/S0376-7388(00)00615-3
43.
Cotes
,
J. E.
,
1993
,
Lung Function: Assessment and Application in Medicine
, 5th ed.,
Blackwell Scientific
,
Oxford
.
44.
Ballermann
,
B.
,
Dardik
,
A.
,
Eng
,
E.
, and
Liu
,
A.
,
1998
, “
Shear Stress and the Endothelium
,”
Kidney Int.
,
54
(
67
), pp.
S100
S108
.10.1046/j.1523-1755.1998.06720.x
45.
Annesini
,
M. C.
,
Marrelli
,
L.
,
Piemonte
,
V.
, and
Turchetti
,
L.
,
2017
, “
Blood Oxygenators and Artificial Lungs
,”
Artificial Organ Engineering
,
Springer
,
London
.10.1007/978-1-4471-6443-2_6
46.
Novalung GmbH
,
2013
, “
Novalung, iLA Activve® System Platform
,” Novalung GmbH, Heilbronn, Germany, accessed Dec. 11,
2020
, https://www.inspiration-healthcare.com/downloads/brochure-85.pdf
47.
Jan
,
Y. J.
,
1988
, “
A Simple Program for Plotting Streamlines and Calculating Residence Times
,”
Commun. Appl. Numer. Methods
,
4
(
6
), pp.
699
707
.10.1002/cnm.1630040602
You do not currently have access to this content.