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Design, fabrication, and characterization of bioactive amphiphilic polymers as cardiovascular therapeutics

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TitleInfo
Title
Design, fabrication, and characterization of bioactive amphiphilic polymers as cardiovascular therapeutics
Name (type = personal)
NamePart (type = family)
Chan
NamePart (type = given)
Jennifer Wing-Yee
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Jennifer Wing-Yee Chan
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author
Name (type = personal)
NamePart (type = family)
Uhrich
NamePart (type = given)
Kathryn E.
DisplayForm
Kathryn E. Uhrich
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Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Fabris
NamePart (type = given)
Laura
DisplayForm
Laura Fabris
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Roth
NamePart (type = given)
Charles M.
DisplayForm
Charles M. Roth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Eknoian
NamePart (type = given)
Michael W.
DisplayForm
Michael W. Eknoian
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
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Text
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theses
OriginInfo
DateCreated (qualifier = exact)
2016
DateOther (qualifier = exact); (type = degree)
2016-05
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2016
Place
PlaceTerm (type = code)
xx
Language
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eng
Abstract (type = abstract)
Recent advancements in cardiovascular drug-eluting stents (DES) have significantly improved clinical outcomes and survival rates in patients with arteries blocked by fat and cholesterol accumulation. Current DES utilize a cytotoxic or immunosuppressive agent to overcome earlier issues of restenosis, or smooth muscle cell (SMC) hyperproliferation, but the drugs and polymer overcoat are associated with an increased risk of late-stent thrombosis, or blood clot formation due to delayed re-endothelialization and hypersensitivity reactions. Both of these issues restrict blood flow and may cause angina, myocardial infarction, and/or death. An alternative therapeutic strategy is to target upstream events in the restenosis and thrombosis cascades, such as high levels of oxidative stress. In this research, bioactive micelles and nanoparticles were developed to minimize cellular interactions of oxidized low-density lipoprotein (oxLDL), which has been shown to induce excessive cellular proliferation and platelet activation. These formulations are comprised of amphiphilic macromolecules (AMs) containing a sugar-based hydrophobic domain and a hydrophilic poly(ethylene glycol) tail. The results indicate that when SMCs are exposed to high levels of oxidized lipid stimuli, AM nanoassemblies inhibited oxLDL uptake, downregulated scavenger receptor expression, and attenuated scavenger receptor gene transcription, and thus significantly suppressed SMC proliferation with minimal cytotoxicity. The potential for bioactive AM delivery was further evaluated as stent coatings, where AMs were self-assembled into monolayer coatings on metal oxide substrates using grafting-from and grafting-to approaches. In the grafting-from technique, molecules were polymerized from the surface in a multi-step synthesis, whereas polymers were pre-synthesized before end-functionalization to the surface in the grafting-to method. Densely packed layers of bioactive AMs gradually released from substrates, significantly suppressing SMC proliferation and platelet adsorption. Variations in the grafting method, functional end group, and linker length yielded a range of AM grafting densities, release rates, and reductions in SMC proliferation and platelet adsorption, suggesting that the bioactive AM release profile can be tuned to match physiological events in the restenosis and thrombosis cascades. Overall, the findings in this thesis highlight the potential of using AM formulations as stand-alone bioactive agents or for controlled therapeutic delivery from coronary stents to minimize restenosis and thrombosis.
Subject (authority = RUETD)
Topic
Biomedical Engineering
Subject (authority = ETD-LCSH)
Topic
Stents (Surgery)
Subject (authority = ETD-LCSH)
Topic
Macromolecules
RelatedItem (type = host)
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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ETD_7041
PhysicalDescription
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electronic resource
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application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xxi, 143 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Jennifer Wing-Yee Chan
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3PC34J2
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Chan
GivenName
Jennifer
MiddleName
Wing-Yee
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-04-14 02:35:26
AssociatedEntity
Name
Jennifer Chan
Role
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Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2018-05-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2018.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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