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Desing of Click Hydrogels for Cell Encapsulation

dc.contributor.advisorWang, Nam Sunen_US
dc.contributor.authorBreger, Joyceen_US
dc.description.abstractThe long-term stability of ionically crosslinked alginate hinders the development of a bioartificial pancreas for the treatment of Type I Diabetes. Ionically crosslinked alginate with divalent cations is traditionally utilized to encapsulate islets of Langerhans serving as a protective barrier between the host's immune system and the donor islets of Langerhans. However, due to ion exchange with monovalent ions from the surrounding serum, alginate degrades exposing donor tissue to the host's immune system. The overall goal of this dissertation was to explore the possibility of utilizing `click' chemistry to introduce covalent crosslinking in alginate for therapeutic cell encapsulation. `Click' chemistry is customarily defined as the Cu (I) catalyzed reaction between an azide and alkyne to form a 1,2,3 triazole ring. To achieve the goal of covalently crosslinked polysaccharides, the following aims were determined: (1) synthesis and characterization of functionalized polysaccharides (alginate and/or hyaluronic acid) with alkyne or azide end groups; (2) measurement and comparison of the stability and transport properties of covalently crosslinked alginate hydrogels to that of ionically crosslinked alginate hydrogels; (3) determination of the inflammatory potential and cytotoxicity of these functionalized polysaccharides and `click' reagents by employing RAW264.7, a murine macrophage cell line under various simulated inflammatory states (with or without endotoxin, with or with out the inflammatory cytokine gamma-interferon); (4) optimization of the `click' reaction for therapeutic cell encapsulation utilizing RIN-5F, a rat insulinoma cell line, while minimizing cytotoxicity and maintaining insulin production; (5) encapsulation of primary porcine islets of Langerhans in either ionically and/or covalently crosslinked alginate capsulation and comparing insulin response to a glucose challenge. The results of these experiments demonstrate the utility of employing `click' chemistry to increase the overall stability of alginate hydrogels while maintaining therapeutic cell function.en_US
dc.titleDesing of Click Hydrogels for Cell Encapsulationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentChemical Engineeringen_US
dc.subject.pqcontrolledBiomedical Engineeringen_US
dc.subject.pqcontrolledChemical Engineeringen_US
dc.subject.pqcontrolledEnvironmental Sciencesen_US
dc.subject.pquncontrolledCovalent Crosslinkingen_US
dc.subject.pquncontrolledHyaluronic Aciden_US
dc.subject.pquncontrolledIslets of Langerhansen_US

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