Page 178 - Biomedical Engineering and Design Handbook Volume 2, Applications

DESIGN OF ARTIFICIAL KIDNEYS 157

glutathione, and other substances are reabsorbed through active, passive, and facilitated transport
mechanisms. The artificial kidney does not reabsorb some of the essential nutrients, such as the
amino acids, small protein, and peptides, etc. Activated charcoal microcapsules have been suggested
51
for use in the artificial kidney. However, there are numerous drawbacks with the charcoal kidney.
There continues to be a need for replacing the other functions of the natural kidney, such the amino
52
acid and peptide reabsorption. Humes et al. are developing a bioengineered artificial kidney device.
5.6 BIOENGINEERED ARTIFICIAL KIDNEY

Recent advances in tissue engineering and tissue culture have created opportunities for the development
of bioengineered artificial kidney devices. Humes et al. 52,53 have successfully developed a bioengi-
neered renal tubule assist device (RAD) by seeding proximal tubule cells on the inner surface of hollow
fibers made of polysulfone. The inner luminal surface of polysulfone was first coated with a synthetic
protein, Pro-Nectin-L, to promote cellular attachment to the surface. Tubule cells were then seeded onto
this surface. For preclinical trials, investigators have extracted tubule cells from pigs. However, for further
studies and clinical trials, they have extracted proximal tubule cells from human postmortem kidney
specimens and transplant discards. After seeding, the bioreactors (tubule-cell–seeded hollow fibers)
were perfused with culture media initially through diffusion and later with convective flow. The biore-
actors were then evaluated for reabsorption protein, amino acids, glucose, etc. Initial experiments were
conducted with tubule cells seeded onto single hollow fibers and then with tubule cells seeded onto com-
mercially available polysulfone catridges. In preclinical anesthetized dog experiments, a commercial
high flux hollow fiber artificial kidney was used to remove waste materials, and the ultrafiltrate from this
artificial kidney was then perfused through the RAD bioreactor cartridge as shown in Fig. 5.10.

To drain

Pump
Return to dog’s vein

From artery
Rad cartridge
(blood flows outside
Hemofilter
the capillaries)
(blood flows inside the Pump
hollow fibers)

Heater

Pump

Flow meter
Bypass
Pressure Heater
monitor
FIGURE 5.10 The bio-artificial kidney being developed by Humes et al. Renal tubule assist device (RAD) is in
series with a hemofilter. Renal tubule cells are grown on the inside wall of a synthetic hollow fiber. The renal tubule
cells produce and/or reabsorb essential hormones. The RAD cartridge consists of the bio-hollow tubes. The waste from
the hemofilter flows through the inside of the bio-hollow tubes and the blood flows on the outside of these tubes in the
RAD cartridge, absorbing the essential hormones produced by the renal tubule cells in the wall of the bio-hollow tube.