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

Share

COinS