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Strategies for improving growth factor function in diabetic wounds

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TitleInfo
Title
Strategies for improving growth factor function in diabetic wounds
Name (type = personal)
NamePart (type = family)
Olekson
NamePart (type = given)
Melissa Ann
NamePart (type = date)
1986-
DisplayForm
Melissa Olekson
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Berthiaume
NamePart (type = given)
Francois
DisplayForm
Francois Berthiaume
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Sofou
NamePart (type = given)
Stavroula
DisplayForm
Stavroula Sofou
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Moghe
NamePart (type = given)
Prabhas
DisplayForm
Prabhas Moghe
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Hsia
NamePart (type = given)
Henry
DisplayForm
Henry Hsia
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = personal)
NamePart (type = family)
Schmidt
NamePart (type = given)
Ann Marie
DisplayForm
Ann Marie Schmidt
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
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-10
CopyrightDate (encoding = w3cdtf)
2014
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Diabetic Foot Ulcers (DFUs) are debilitating non-healing wounds that often lead to amputation. The dermal scaffold is a promising treatment strategy that provides a template for cell migration and vascularization. Nevertheless, they fail in many instances due to the pro-inflammatory state of the wound, which includes increased matrix metalloproteases (MMPs) that degrade growth factors. MMPs act on both endogenous and exogenous growth factors that are added to the wound to aid in healing. Therefore, the goal of this project is to improve growth factor treatments delivered in dermal scaffolds by specifically packaging them to survive the diabetic milieu. The growth factor used here, stromal cell-derived factor-1 (SDF-1) is a chemokine that binds to the CXCR4 receptor on stem and progenitor cells; it is down-regulated in diabetes. This dissertation aims to improve SDF-1 action by blocking the pro-inflammatory receptor for advanced glycation end products (RAGE) pathway with soluble RAGE (sRAGE) and improve SDF-1 persistence using a liposome delivery system. To test the effectiveness of SDF-1, a transwell migration assay was developed, where Human Leukemia-60 (HL-60) cells, that contain the CXCR4 receptor, migrate through a porous membrane towards a supply of SDF-1. The major finding using this assay was that, as SDF-1 increases, percent cell migration increases. In addition, when HL-60 cells are pre-treated with 25mM extra glucose in cell media for 24 hours, cell migration decreased compared to cells cultured with plain media and media supplemented with L-glucose. sRAGE treatment reversed this impairment and restored migration. The mechanism causing this phenomenon is the increased superoxide ion (O2-) in increased glucose cultures, which was measured through dihydroethidium. The SDF-1 liposomes were created using standard self assembly methods and also induced HL-60 cell migration in the transwell. SDF-1 liposomes maintained the induction of a calcium response associated with SDF-1 signaling. The SDF-1 liposomes also rapidly and uniformly infiltrated dermal scaffolds Alloderm® and Integra®. In an in vivo diabetic excisional wound model, sRAGE alone was not enough to restore SDF-1 function. However, SDF-1 liposomes sped up wound closure by 1 week over the controls through increased dermal cell proliferation and promotion of wound contraction.
Subject (authority = RUETD)
Topic
Biomedical Engineering
Subject (authority = ETD-LCSH)
Topic
Wounds and injuries--Treatment
Subject (authority = ETD-LCSH)
Topic
Diabetic foot
Subject (authority = ETD-LCSH)
Topic
Diabetes--Complications
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5712
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiii, 84 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Melissa Ann Olekson
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T37P8XNW
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Olekson
GivenName
Melissa
MiddleName
Ann
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-06-16 10:34:00
AssociatedEntity
Name
Melissa Olekson
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
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)
2014-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2015-05-02
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 2nd, 2015.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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