Tissue engineering - Biomedical Engineering Desk Reference - page 642

strategies have proven successful, and there is abundant
evidence of survival of xenogenic cells, in these limited
circumstances, for 3 to 6 months or longer. In contrast,
encapsulated xenogenic cells rarely survive much beyond
14 to 28 days when implanted subcutaneously or in-
traperitoneally in immunocompetent hosts.
Two mechanisms are invoked to explain the inability
of membranes to universally protect xenogenic implants,
and the different fates of encapsulated allogeneic and
xenogeneic cells. First, membranes are not ideally semi-
permeable and thus allow passage of small quantities of
large immunomolecules, including complement and both
elicited and preformed immunoglobulins. Such agents
are far more active against xenogenic cells than against
allogenic grafts. A second problem is that soluble antigens
''leak'' from cell surfaces or are released upon cell ne-
crosis. These protein constituents are not conserved be-
tween species and are, in varying degrees, immunogenic.
Their gradual release results in a localized inflammatory
response in the neighborhood of the membrane, readily
visualized by histology. Inflammatory cells express a
number of low-molecular-weight toxins (including free
radicals and cytotoxic cytokines) that pass through the
membrane and attack the cells inside. Note that this

mechanism requires a local nidus of inflammatory tissue
and is thus unlikely to be encountered when implants are
placed in cell-free fluid cavities. It is also not significant
with allogenic cells whose only non-self proteins are
confined to the MHC system.
Interestingly, pharmacological immunosuppression
has rarely been used in conjunction with encapsulation,
though on theoretical grounds the combination of me-
chanical and chemical agents would likely prove highly
effective.

Devices for immunoisolation

Depending on size and shape, implantable immuno-
isolation device designs can be categorized as either
microcapsules or macrocapsules. Microcapsule beads are
illustrated in Fig. 7.1.3-2 (upper right), along with other
materials popular for immunoisolation. A current
macrocapsule design is shown in Fig. 7.1.3-3 . These dif-
ferent designs all share the common components of
a permselective membrane, an internal matrix, and the
living encapsulated tissue. Macrocapsules are small (100-
600 m m, 0.01-0.06 10 4

cm in diameter) spherical

Fig. 7.1.3-2 Materials used as matrices or barrier materials. Micrographs or photomacrographs of hydrophilic materials in the form of
matrices (top left) and microcapsules (top right) and of hydrophobic materials in the form of foams (bottom left) and membranes for use in
macrocapsules (bottom right).