Bioactive hydrogels
for immunoisolation
Ideal hydrogel material for islet encapsulation is one that
can safely encapsulate islets while completely free the patients from
immunosuppressants. Polyethylene glycol (PEG) hydrogels, for example, have been
demonstrated useful in islet encapsulation as their semi-permeable environments
not only allow for free diffusion of nutrients and insulin but also provide
partial immunoisolation to the allogenic or xenogenic islets. Unfortunately,
clinical trials of microencapsulated islets have shown limited success, possibly
due to the infiltration of small cytotoxic molecules such as tumor necrosis
factor alpha α (TNFα) and interleukin 1β (IL-1β). The requirement of high gel
permeability for facile nutrient-waste exchange and insulin diffusion prohibits
the use of highly crosslinked hydrogels for islet encapsulation. Therefore,
small cytotoxic molecules can diffuse freely into the gel and cause graft
failure. With the objectives of enhancing encapsulated islet survival and
function in mind, I am interested in the fabrication and characterization of
novel, bioactive immunoisolation hydrogels that selectively prevent infiltration
of cytotoxic cytokines produced by inflammatory cells such as macrophages. This
will be achieved by identifying and incorporating affinity peptidyl
cytokine-binders into the otherwise inert PEG hydrogels. It is expected that
encapsulated islet survival will be greatly prolonged within these bioactive,
cytokine-scavenging hydrogels.
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