Biomedical Engineering Reference
In-Depth Information
administered insulin cannot match the natural response of insulin producing cells to
food intake, exercise and stress. While whole organ (pancreas) and islet transplants
are an alternative, as with any transplantation scenario, the need far outweighs the
availability of supply of donor organs. As well, the patient would need to undergo a
lifelong immunosuppressive regime. An alternative method under investigation is
the transplantation of xenogenic or allogenic insulin producing cells sequestered in
a device that could act like an artifi cial pancreas. This artifi cial organ would be
made of biocompatible materials in which insulin producing cells will live and
function normally. The device would be implanted into a patient in order to provide
continuous insulin control through interaction with the body's biochemical signals.
The device itself should be engineered to house and protect the cells from the host's
immune system thereby negating the need for immunosuppressive drugs.
The success of a tissue-engineered construct when transplanted into a living
being will depend foremost on the response it elicits from the host's immune sys-
tem. Immune rejection of the construct is due to antibody recognition of foreign
antigens present on either the cells or the scaffold material (if biological materials
are used). Researchers have attempted to overcome this recognition of foreign anti-
gens by creating immunoisolation devices to house the engineered tissue construct.
These devices block antibodies from getting at the transplanted cells by creating a
physical barrier to diffusion into the scaffold. The key to these immunoisolation
devices is to block antibodies from entering but allow nutrients in and wastes and
cellular products, most specifi cally insulin, out. To do this, porous materials (e.g.
polymers) have been investigated as size-selective barriers. The problem with these
materials, however, is that they usually exhibit a range of pore sizes that do not
adequately block all antibodies. Also, these materials typically have distances of
100-200 mm over which molecules must diffuse in order to enter or leave the encap-
sulation device. These relatively large diffusion distances can severely hinder the
dynamic response of cells to changing conditions in the body. For immunoprotec-
tion, a well-controlled pore size is needed and for dynamic control of insulin levels,
as thin a barrier as possible between the host and the cells is desired. Microfabrication
and nanofabrication technology has allowed for the construction of thin membranes
with precisely controlled pore size and distribution.
Nanoporous capsules with 5 mm thick membranes and uniform pore dimensions
and pores sizes down to 7 nm were developed for islet cell transplantation using
bulk and surface micromachining techniques (Leoni and Desai
2004
) . Studies with
these capsules have shown that cell viability and functionality were not compro-
mised by the encapsulation (Desai et al.
2004
). The porous membranes of these
capsules were shown to provide suffi cient insulin and glucose diffusion for nutrient
exchange for the encapsulated cells. These membranes also showed an almost com-
plete deselection of immunoglobulin G (IgG), the most abundant immunoglobulin
in the body, over extended periods of time. In vivo studies done on rats with encap-
sulated insulinoma cells showed a reversal in diabetes and normal blood glucose
levels over 2 weeks (total encapsulation time was 14 days).
Capsules with porous membranes created via the two-step anodization process
used to create the bone-cell scaffolds are also being used for encapsulating insulin
producing cells (La Flamme et al.
2005
). This process creates pores of a slightly
