Type I diabetes is a genetic, autoimmune disorder that affects 1 in every 300
people under the age of 20 nationwide. The body’s immune system attacks and
destroys the insulin producing beta cells of the pancreas. The most common
treatment for the disease is daily injections of insulin, which require frequent
glucose monitoring and patient compliance. Islet transplantation is a promising
treatment for the disease where many research efforts are focused. Currently,
patients who receive these grafts are treated systemically with immunosuppressant
drugs to minimize the body’s rejection of the transplanted foreign islet cells.
Consequently, immunosuppression turns off the patient’s immune system making
them more susceptible to other diseases and illnesses.
Immunoprotection of islets by encapsulation with an inert, semi-permeable material
can minimize cell-cell mediated destruction by immune cells and still allow for
nutrient, glucose, O2, and insulin transport. However, these immune cells that
are recruited to the site of implantation secrete other molecules that can diffuse
through the passive barrier, such as cytokines and proteases which have an adverse
effect on the viability of encapsulated islet cells. There is a need for an
active barrier system that will provide localized immunosuppression in the
surrounding environment, thus, enhancing tolerance of the grafted tissue.
This project aims to use bioconjugation techniques to covalently incorporate
anti-inflammatory drugs attached to enzyme cleavable peptides into a
poly(ethylene glycol) (PEG) hydrogel. Upon neutrophil (immune cell) activation,
elastase is secreted which can penetrate the gel network
and cleave its respective substrate releasing a therapeutic
into the localized environment. This biomaterial will act as
a physical, active barrier and protect encapsulated cells
from the in vivo environment.
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Alex
Aimetti 
