Page 404 - Academic Press Encyclopedia of Physical Science and Technology 3rd Chemical Engineering

P1: GLQ Final Pages
Encyclopedia of Physical Science and Technology EN009K-419 July 19, 2001 20:57

Membranes, Synthetic, Applications 339

Advances in fabrication technology have made possible nate coating, effectively creating a large number of sin-
theproductionofverypreciselyalignedandspacedhollow gle bioreactors. Upon injection into tumor sites of an an-
fibers. Flow across such fiber arrays can thus be regulated imal, the cells released endostatin continually to cause
to minimize boundary layer effects or blind spots; very anti-angiogenesis, or starvation of the blood supply to the
high mass transfer efficiencies have been achieved in this tumor. The result was dramatic shrinkage of the tumor
manner. itself. In this example, the alginate coating on each cell
serves all the selective permeation and protective func-
tions of an artificial organ membrane. It is not difficult
D. Artificial Organs
to envision dramatic progress being made in this area of
Membrane-based artificial organs are sophisticated biore- biomedicine—and the enabling role played by synthetic
actors. In fact, experience in the area of mammalian cell membrane science and technology.
culture probably first inspired, and then contributed di- On the commercial front, an artificial liver system has
rectlytothedesignandengineeringofdevicesandsystems reached advanced clinical trial stage. Based on pig hep-
intended as substitutes for healthy human organs. There atocytes immobilized in a hollow-fiber membrane mod-
is certainly great appeal in being able to encapsulate liv- ule, this system provides temporary life support until a
ing organ cells in a synthetic membrane, keeping them liver from a human donor is available for transplantation
viable by providing favorable microenvironments while (Fig. 50). Also under development is an artificial pancreas
protecting them from immunological attack by the host, intended as a permanent replacement of the native organ
andextractingmetaboliteswiththerapeuticfunctionsfrom (Fig. 51).
the cells.
However, unlike bioreactors described previously, E. Controlled Release
which are used to perform a sequence of well-defined
Safe and efficient use of many pharmaceuticals and ther-
biochemical conversions, artificial organs must provide
apeutic agents in general requires that the dosage and de-
the highly complex metabolic and endocrine functions
of the native organ. This has not yet been accomplished, livery rate be precisely regulated. An agent must reach
partly because of the difficulty of duplicating all essential
regulatory and feedback mechanisms between an organ
and its host, and partly because successful demonstration
of artificial organ systems, particularly in humans, is very
expensive and subject to close institutional and regulatory
scrutiny. Finally, membrane-based artificial organs face
competition from other approaches to organ replacement,
such as xenotransplantation or regeneration of organs
from stem cells.
An early demonstration of the artificial organ concept
consisted of sealing a small number of bovine cells in the
lumen of a microporous hollow fiber. The cells were se-
lected for their ability to secrete a mixture of analgesic
biomolecules. Implanting the hollow fiber in the body of
a patient places the encapsulated cells under physiological
conditions sufficiently favorable for them to function, yet
protected from immunological attack by the host—that
is, the patient’s own defense mechanism against xeno-
geneic cells. The cells responded by secreting the expected
pain-killing agents to the patient. Considerable progress
has been made in the methods of encapsulating cells and
the design of membrane materials and structure, and the
range of target therapies (Lysaght and Aebischer, 1999;
Li, 1998).
This approach continues to stimulate innovations in
immunoisolated cell therapies. In a very recent animal
study (“Study touts,” 2000), cells capable of producing FIGURE 50 Schematic of advanced artificial liver system under-
endostatin were encapsulated individually with an algi- going clinical trials (Circe Biomedical, Inc., Lexington, MA).