Publication Date
2015-07-30
Availability
Embargoed
Embargo Period
2017-07-29
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PHD)
Department
Biochemistry and Molecular Biology (Medicine)
Date of Defense
2015-05-29
First Committee Member
Cherie L. Stabler
Second Committee Member
Allison L. Bayer
Third Committee Member
Alessia Fornoni
Fourth Committee Member
Sapna K. Deo
Fifth Committee Member
Ashutosh Agarwal
Abstract
Type 1 Diabetes (T1D) is a life-long autoimmune disease where immune cells destroy the beta cells of the Islets of Langerhans, eliminating the patient’s ability to secrete insulin in response to glucose. While the implantation of allogeneic islets into T1D patients can restore glucose control, the duration of the islet transplant is compromised by immune attack through both innate and adaptive pathways. Therefore, we sought to engineer biomaterial strategies to lessen immunological attack and improve transplant outcomes. This dissertation presents immunomodulatory biomaterials seeking to modulate the local transplant microenvironment, specifically: 1) the chemoselective tethering of TGF-β1 to PEG brush surfaces on encapsulating biomaterials to locally direct effector T cell responses; and 2) the layer-by-layer coating of encapsulating platforms with cerium oxide nanoparticle composites to locally protect encapsulated cells from free radical damage. The overall objective of this work was to engineer biomaterials with the capacity to modulate immune responses and to enhance islet viability and function at the transplant site.
Keywords
Biomaterials; Immunomodulation; Staudinger ligation; Immunoisolation; Nanoceria; Regulatory T cells
Recommended Citation
Yang, Ethan Y., "Development of Immunomodulatory Biomaterials for the Islet Transplant Niche" (2015). Open Access Dissertations. 1513.
http://scholarlyrepository.miami.edu/oa_dissertations/1513