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Advisory Committee Chair

Ho-Wook Jun

Advisory Committee Members

Dale S Feldman

Jeonga Kim

Anath Shalev

Timothy M Wick

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

In an attempt to treat type 1 diabetes, pancreatic islet transplantation (PIT) had been studied, but only 10% of recipients showed maintained insulin independence after 5-year post-islet transplantation, indicating that there remains a constant demand for improving the efficacy of PIT. For a successful PIT, critical factors should be addressed: immune protection, revascularization, and ECM-microenvironment reconstitution. Among them, this study was aimed to develop an ECM mimetic scaffold that reconstitutes the ECM derived microenvironment for an isolated beta cell and islet. A growing body of studies also indicates that the pancreatic ECM is of importance in islet survival and function. Hence, inscribing the dynamic characteristics of the pancreatic ECM within a biomimetic scaffold could offer an advanced strategy for PIT. In this dissertation, biomimetic self-assembled nanomatrix scaffolds composed of peptide amphiphiles (PAs) were explored to replicate the favorable native ECM microenvironment essential for beta cell or islet survival and function. Using MIN6 ß cell lines, the PA scaffold inscribed with laminin-1 derived cell adhesive ligands was successfully developed to provide an islet ECM mimic environment for supporting beta cell functionality. While incorporating cell-adhesive sequences, a nitric oxide (NO)-releasing PA scaffold was also developed to providing ß cells with a nitric oxide-releasing microenvironment. The NO releasing PA scaffold improved MIN6 beta cell's survival and function, demonstrating the potential of the PA scaffold in improving the efficacy of PIT with an expectation of enhanced revascularization by NO. In addition, the biomimetic self-assembled PA nanomatrix supported improved islet survival and function in vitro as well. Through achieving fairly good islet survival and function for 14 days, the potential of the PA scaffold was demonstrated as an intermediary scaffold. These results demonstrate that the PA scaffold can allow the host integration of islets, for which at least 10-12 days is required. Overall, this dissertation demonstrated that the biomimetic self-assembled nanomatrix provide a feasible biomaterial strategy that improves the efficacy of PIT, which has been known to be a promising treatment for type 1 diabetes.

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