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http://hdl.handle.net/11375/17363
Title: | Polyelectrolytes for Therapeutic Cell Encapsulation |
Authors: | Mazumder, Mohammad |
Advisor: | Stover, Harald D. H. |
Department: | Chemistry |
Keywords: | Cell, Cell encapsulation, therapeutic, protein, trannsplant, immune-isolating, gentic, microcapsules, alginate, APA, alginate-poly-L-lysine-alginate, ions, biocompatibility |
Publication Date: | Jun-2009 |
Abstract: | <p> Cell encapsulation aims at the delivery of a therapeutic protein to a patient from transplanted cells. Conventional approaches involve immune-isolating cell lines that have been genetically modified to express a therapeutic protein, in alginate-based microcapsules. The long-term success of this approach hinges on the structural stability of the microcapsules, as well as their ability to maintain an environment suitable for the long-term survival of encapsulated cells. The most commonly studied type of microcapsule is the alginate-poly-Llysine-alginate (APA) microcapsule. However, the main concern with AP A microcapsules is the Joss of structural integrity during long-term implantation due to the exchange of calcium ions with other physiological ions, as well as the loss of the polyelectrolyte overcoats. </p> <p> In order to increase the structural stability of the microcapsules, we developed and characterized a number of synthetic polyelectrolytes that undergo phase separation upon complexation, and which are capable of forming covalent cross-links. These reactive polyelectrolytes are designed to take the place of poly-L-lysine and the outer alginate layer. We also explored combining cross-linkable synthetic polyanions with sodium alginate to strengthen the Ca Alginate core, by forming a core cross-linked network extending throughout the microcapsules. The polyelectrolyte complexes, encapsulation processes and microcapsule properties were studied in detail using extensive characterization techniques, including collaborative work on cell viability and host-immune response. </p> <p> Overall, this thesis describes a novel approach and prom1smg materials for cell encapsulations that offer enhanced microcapsule resistance to chemical and mechanical stresses, while preserving the desired biocompatibility. These materials may ultimately be useful for clinical immunosuppressive therapies. </p> |
URI: | http://hdl.handle.net/11375/17363 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Mazumder_Mohammad_AJ_2009June_PhD.pdf | 69.34 MB | Adobe PDF | View/Open |
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