Generating local
immunosuppression by incorporating anti-fas antibody
into a polymer brush
I utilize biomaterials to generate local immunosuppression.
When a patient develops type I (juvenile) diabetes, his or her immune system
produces autoimmune B cells (antibody response) and T cells (cytotoxic
response). This autoimmunity leads to the destruction of insulin-producing
β-cells within pancreatic islets of Langerhans. While conventional type I
diabetes therapy centers around insulin replacement, β-cell transplantation
could potentially cure juvenile diabetes. Unfortunately, β-cell transplantation
is currently limited by high rejection rates. Transplant longevity can be
increased by encapsulating β-cells in hydrogel networks because self-reactive
antibodies are unable to enter the hydrogel network. Over time, however, grafts
are eventually rejected due to T cell mediated processes.
To reduce T cell mediated transplant rejection, I am utilizing living radical
polymerization (LRP) strategies to graft a polymer brush, composed of PEG400
acrylate monomer and pendant acrylated anti-fas antibodies, on the surface of an
islet graft. When anti-fas binds the fas receptor on T cells, it triggers T cell
apoptosis. Thus, polymerizing a dense network of anti-fas antibody on the
surface of an islet graft should decrease the local T-cell concentration and
improve transplant longevity. Presently, I have focused on generating,
characterizing, and optimizing polymer brush formation in addition to developing
a novel, water-soluble photoiniferter for the purpose of conducting LRP directly
on the surface of a hydrogel.
Left: Labeled (green) primary antibody incorporated into a polymer brush
Right: Labeled (red) secondary antibody is able to access the primary antibody
in the polymer brush
|
