Publication Date

2013-10-18

Availability

Embargoed

Embargo Period

2014-10-18

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

2013-09-13

First Committee Member

Cherie L. Stabler

Second Committee Member

Fotios Andreopoulos

Third Committee Member

Edward Dauer

Fourth Committee Member

Peter Buchwald

Fifth Committee Member

Angel Kaifer

Sixth Committee Member

Antonello Pileggi

Abstract

Type 1 Diabetes Mellitus (T1DM) is a disease characterized by the autoimmune destruction of beta cells within the pancreatic islet. Islet replacement via transplantation of allogeneic islets demonstrates promise as a viable cure for this disease. Despite clinical success in the mitigation of T1DM symptoms, the islet transplant technique has been plagued by issues that limit graft survival and duration. Inflammation plays a significant role in the destruction of islet grafts, particularly during early engraftment. Therefore, strategies that provide alleviation of inflammation could substantially improve graft outcomes, particularly in the design of alternative islet graft transplant environments. This dissertation presents two biomaterial-based strategies for the local mitigation of inflammation in the islet transplant microenvironment: 1) the development and optimization of an implantable anti-inflammatory drug-eluting organosilicone construct; and 2) the supplementation of islets with antioxidant cerium oxide nanoparticle (CONP)-doped encapsulation polymers. The aim of this work was to develop biomaterials with the capacity to reduce local inflammation in an islet transplant site, thereby improving long-term viability and function of the transplanted cells.

Keywords

Islet transplantation; biomaterials; inflammation; drug delivery; encapsulation; cerium oxide nanoparticles

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