Full metadata
Title
Development of a Hydrogel Macroencapsulation Device for Improved Long-Term Islet Survival Using Injection Molding and Oxygen Modeling-Aided Design
Description
Allogeneic islet transplantation has the potential to reverse Type 1 Diabetes in patients. However, limitations such as chronic immunosuppression, islet donor numbers, and islet survival post-transplantation prevent the widespread application of allogeneic islet transplantation as the treatment of choice. Macroencapsulation devices have been widely used in allogeneic islet transplantation due to their capability to shield transplanted cells from the immune system as well as provide a supportive environment for cell viability, but macroencapsulation devices face oxygen transport challenges as their geometry increases from preclinical to clinical scales. The goal of this work is to generate complex 3D hydrogel macroencapsulation devices with sufficient oxygen transport to support encapsulated cell survival and generate these devices in a way that is accessible in the clinic as well as scaled manufacturing. A 3D-printed injection mold has been developed to generate hydrogel-based cell encapsulation devices with spiral geometries. The spiral geometry of the macroencapsulation device facilitates greater oxygen transport throughout the whole device resulting in improved islet function in vivo in a syngeneic rat model. A computational model of the oxygen concentration within macroencapsulation devices, validated by in vitro analysis, predicts that cells and islets maintain a greater viability and function in the spiral macroencapsulation device. To further validate the computational model, pO2 Reporter Composite Hydrogels (PORCH) are engineered to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) magnetic resonance imaging approach. Overall, a macroencapsulation device geometry designed via computational modeling of device oxygen gradients and validated with magnetic resonance (MR) oximetry imaging enhances islet function and survival for islet transplantation.
Date Created
2023
Contributors
- Emerson, Amy (Author)
- Weaver, Jessica (Thesis advisor)
- Kodibagkar, Vikram (Committee member)
- Sadleir, Rosalind (Committee member)
- Stabenfeldt, Sarah (Committee member)
- Wang, Kuei-Chun (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
135 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.2.N.190904
Level of coding
minimal
Cataloging Standards
Note
Partial requirement for: Ph.D., Arizona State University, 2023
Field of study: Biomedical Engineering
System Created
- 2023-12-14 01:47:05
System Modified
- 2023-12-14 01:47:12
- 11 months 1 week ago
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