Abstract
For the development and implementation of primary human cell- and stem cell-based applications in regenerative medicine, large amounts of cells with well-defined characteristics are needed. Such cell quantities can be obtained with the use of hollow fiber-based bioreactors. While the use of such bioreactors generally requires a perfusion circuit, the configuration and complexity of such circuits is still in debate. We evaluated various circuit configurations to investigate potential perfusate volume shifts in the arterial and venous sides of the perfusion circuit, as well as in the feed and waste lines. Volume shifts with changes in flow conditions were measured with graduated bubble traps in the circuit, and perfusion pressures were measured at three points in the circuits. The results of this study demonstrate that the bioreactor perfusion circuit configuration has an effect on system pressures and volume shifts in the circuit. During operation, spikes in post-bioreactor pressures caused detrimental, potentially dangerous volume shifts in the feed and waste lines for configurations that lacked feed pumps and/or waste line check valves. Our results indicate that a more complex tubing circuit adds to safety of operation and avoids technical challenges associated with the use of large-scale hollow fiber bioreactors (e.g., for extracorporeal liver support or erythrocyte production from hematopoietic stem cells), including volume shifts and the need for a large reservoir. Finally, to ensure safe use of bioreactors, measuring pre-, intra-, and post-bioreactor pressures, and pump operation control is also advisable, which suggests the use of specifically developed bioreactor perfusion devices.
| Original language | English |
|---|---|
| Pages (from-to) | 410-421 |
| Number of pages | 12 |
| Journal | International Journal of Artificial Organs |
| Volume | 34 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2011 |
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Keywords
- Bioartificial liver
- Bioreactors
- Hematopoietic stem cells
- Perfusion circuit
- Perfusion pressure
- Volume shifts
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
- Bioengineering
- Medicine (miscellaneous)
Cite this
Perfusion circuit concepts for hollow-fiber bioreactors used as in vitro cell production systems or ex vivo bioartificial organs. / Balmert, Stephen C.; McKeel, Daniel; Triolo, Fabio; Gridelli, Bruno; Zeilinger, Katrin; Bornemann, Reiner; Gerlach, Jörg C.
In: International Journal of Artificial Organs, Vol. 34, No. 5, 05.2011, p. 410-421.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Perfusion circuit concepts for hollow-fiber bioreactors used as in vitro cell production systems or ex vivo bioartificial organs
AU - Balmert, Stephen C.
AU - McKeel, Daniel
AU - Triolo, Fabio
AU - Gridelli, Bruno
AU - Zeilinger, Katrin
AU - Bornemann, Reiner
AU - Gerlach, Jörg C.
PY - 2011/5
Y1 - 2011/5
N2 - For the development and implementation of primary human cell- and stem cell-based applications in regenerative medicine, large amounts of cells with well-defined characteristics are needed. Such cell quantities can be obtained with the use of hollow fiber-based bioreactors. While the use of such bioreactors generally requires a perfusion circuit, the configuration and complexity of such circuits is still in debate. We evaluated various circuit configurations to investigate potential perfusate volume shifts in the arterial and venous sides of the perfusion circuit, as well as in the feed and waste lines. Volume shifts with changes in flow conditions were measured with graduated bubble traps in the circuit, and perfusion pressures were measured at three points in the circuits. The results of this study demonstrate that the bioreactor perfusion circuit configuration has an effect on system pressures and volume shifts in the circuit. During operation, spikes in post-bioreactor pressures caused detrimental, potentially dangerous volume shifts in the feed and waste lines for configurations that lacked feed pumps and/or waste line check valves. Our results indicate that a more complex tubing circuit adds to safety of operation and avoids technical challenges associated with the use of large-scale hollow fiber bioreactors (e.g., for extracorporeal liver support or erythrocyte production from hematopoietic stem cells), including volume shifts and the need for a large reservoir. Finally, to ensure safe use of bioreactors, measuring pre-, intra-, and post-bioreactor pressures, and pump operation control is also advisable, which suggests the use of specifically developed bioreactor perfusion devices.
AB - For the development and implementation of primary human cell- and stem cell-based applications in regenerative medicine, large amounts of cells with well-defined characteristics are needed. Such cell quantities can be obtained with the use of hollow fiber-based bioreactors. While the use of such bioreactors generally requires a perfusion circuit, the configuration and complexity of such circuits is still in debate. We evaluated various circuit configurations to investigate potential perfusate volume shifts in the arterial and venous sides of the perfusion circuit, as well as in the feed and waste lines. Volume shifts with changes in flow conditions were measured with graduated bubble traps in the circuit, and perfusion pressures were measured at three points in the circuits. The results of this study demonstrate that the bioreactor perfusion circuit configuration has an effect on system pressures and volume shifts in the circuit. During operation, spikes in post-bioreactor pressures caused detrimental, potentially dangerous volume shifts in the feed and waste lines for configurations that lacked feed pumps and/or waste line check valves. Our results indicate that a more complex tubing circuit adds to safety of operation and avoids technical challenges associated with the use of large-scale hollow fiber bioreactors (e.g., for extracorporeal liver support or erythrocyte production from hematopoietic stem cells), including volume shifts and the need for a large reservoir. Finally, to ensure safe use of bioreactors, measuring pre-, intra-, and post-bioreactor pressures, and pump operation control is also advisable, which suggests the use of specifically developed bioreactor perfusion devices.
KW - Bioartificial liver
KW - Bioreactors
KW - Hematopoietic stem cells
KW - Perfusion circuit
KW - Perfusion pressure
KW - Volume shifts
UR - http://www.scopus.com/inward/record.url?scp=79959283243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959283243&partnerID=8YFLogxK
U2 - 10.5301/IJAO.2011.8366
DO - 10.5301/IJAO.2011.8366
M3 - Article
C2 - 21623585
AN - SCOPUS:79959283243
VL - 34
SP - 410
EP - 421
JO - International Journal of Artificial Organs
JF - International Journal of Artificial Organs
SN - 0391-3988
IS - 5
ER -