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ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

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(Wanless, 1999). This low value could bring the hepatocytes to the required standard of<br />

viability and function. In vitro, hepatocytes showed performance over a range of inlet<br />

oxygen partial pressure from 75 to 380 mmHg, and being problematical with lower and<br />

higher inlet oxygen partial pressure.<br />

The results indicated that a silicone rubber membrane of Dm of 16x10 -5 is the best choice<br />

for the outer membrane to ensure cells are oxygenated. The model predicted that the cells<br />

in the annulus could be oxygenated similar to those found the native liver even at high cell<br />

density (figure 7.9, 7.10a and 7.11a). Previous experimental studies showed that the<br />

hepatocytes become functionally impaired below 2 mmHg. At Vmax=100nmol/(cm 3 s) and<br />

silicone rubber of Dm=16x10 -7 (figure 7.11b), the model predicted values of PO2 in the cell<br />

compartment less than 1mmHg over the entire axial length for pG of 40-150mmHg. When<br />

Vmax was 25nmol/(cm 3 s), the results showed (for Dm=16x10 -7 ) the annulus PO2<br />

decreasing from 6, 4.2 and 3.5 mmHg at entryto 1.2, 0.5 and 0.3 (PG = 150, 70, 40 mmHg,<br />

respectively) and remains constant for the next 50% axial length. This decrease in the<br />

annulus PO2 may be caused by initial increase in the cells OCR whereas plasma enters the<br />

annulus for detoxification.<br />

7. CONCULOSION<br />

FIF bioreactor for hepatocytes was developed. This bioreactor has a separate integral<br />

oxygenation in the outermost compartment by the creation of a third space namely<br />

compartment C. This integral oxygenation compartment can easily oxygenate the cells in<br />

the annulus to levels higher than 2 mmHg; ensuring that the cells are functional and viable.<br />

8. REFERENCES<br />

1. Mazariegos GV, Kramer DJ and Lopez RC. (2001),Safety observations in the phase<br />

I clinical evaluation of the Excorp medical BLSS after the first four patients.<br />

ASAIO . Vol. 47: pp 471-475.<br />

2. Gerlach JC, Lemmens P, Schon M, Janke J, Rossaint R, Busse B, Puhl G and<br />

Neuhaus P. (1997). Experimental evaluation of a hybrid liver support system.<br />

Transplantation Proceedings. Vol 29 : pp 852.<br />

3. Watanabe FD, Arnaout WS, Ting P, Navarro A, Khalili T, Kamohara Y, Kahaku E,<br />

Rozga J and Demetriou AA. (1999). Artificial liver. Transplantation proceeding.<br />

Vol. 31. (2): pp 371-373.<br />

4. Wolfe SP, Hsu E, Reid LM and Macdonald JM. (2002). A novel multi-coaxial<br />

hollow fibre bioreactor for adherent cell types. Part 1: Hydrodynamic Studies.<br />

Biotechnology and Bioengineering.Vol. 77 (1) : pp 83-90.<br />

5. Hay PD, Veitch AR, Smith MD, Cousins RB, Gaylor JDS. 2000. Oxygen transfer in<br />

a diffusion-limited hollow-fibre bioartificial liver. Artificial Organs Vol. 24(4) pp<br />

278-288.

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