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The use of stromal cell derived growth factor 1 -- elastin like peptide fusion protein nanoparticles to improve chronic skin wounds
Descriptive
TitleInfo
Title
The use of stromal cell derived growth factor 1 -- elastin like peptide fusion protein nanoparticles to improve chronic skin wounds
Name
(type = personal)
NamePart
(type = family)
Yeboah
NamePart
(type = given)
Agnes
NamePart
(type = date)
1981-
DisplayForm
Agnes Yeboah
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Yarmush
NamePart
(type = given)
Martin l
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Martin l Yarmush
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Advisory Committee
Role
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chair
Name
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NamePart
Rutgers University
Role
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(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
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school
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Text
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theses
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DateCreated
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2016
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2016-05
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2016
Place
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xx
Language
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eng
Abstract
(type = abstract)
Chronic skin wounds are characterized by poor re-epithelialization, angiogenesis and granulation. Previous work demonstrated that topical stromal cell-derived growth factor-1 (SDF1) promotes neovascularization, resulting in faster re-epithelialization of skin wounds in diabetic mice. However, the clinical usefulness of such bioactive peptides is limited because they are rapidly degraded in the wound environment due to high levels of proteases. The goal of this project was to develop a novel fusion protein comprising of SDF1 and an elastin like peptide (ELP), which could be used as a therapeutic alternative to recombinant SDF1, for the treatment of chronic skin wounds. ELPs are derivatives of tropoelastin with repeats of VPGXG, where X can be any natural amino acid except Proline. The dissertation aimed to characterize the physical properties of the SDF1-ELP fusion protein, demonstrate its in vitro and in vivo bioactivity and understand its mechanism of action. We showed that SDF1-ELP conferred the ability to self-assemble into nanoparticles. The fusion protein showed binding characteristics similar to that reported for free SDF1 to the CXCR4 receptor. The biological activity of SDF1-ELP, as measured by intracellular calcium release in HL60 cells was dose dependent, and very similar to that of free SDF1. SDF1-ELP monomers promoted the migration of cells similar to SDF1, and the fusion protein promoted tube formation and capillary-like networks similar to SDF1. In contrast, SDF1-ELP was found to be more stable in elastase and in wound fluid than SDF1. Likewise, the biological activity of SDF1-ELP in vivo was significantly superior to that of free SDF1. When applied to full thickness skin wounds in diabetic mice, wounds treated with SDF1-ELP nanoparticles were 95% closed by day 21, and fully closed by day 28, while wounds treated with free SDF1 and other controls took 42 days to fully close. In addition, the SDF1-ELP nanoparticles increased the amount of vascular endothelial cells, and the epidermal and dermal layer of the healed wound, as compared to the other groups. SDF1-ELP is a promising agent for the treatment of chronic skin wounds.
Subject
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Topic
Chemical and Biochemical Engineering
Subject
(authority = ETD-LCSH)
Topic
Skin--Wounds and injuries
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
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ETD_7062
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (xvi, 116 p. : ill.)
Note
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Ph.D.
Note
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Includes bibliographical references
Note
(type = statement of responsibility)
by Agnes Yeboah
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
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doi:10.7282/T3D50Q5G
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
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Yeboah
GivenName
Agnes
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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2016-03-16 12:29:01
AssociatedEntity
Name
Agnes Yeboah
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Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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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
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2016-05-31
DateTime
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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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