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The use of stromal cell derived growth factor 1 -- elastin like peptide fusion protein nanoparticles to improve chronic skin wounds
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Yeboah, Agnes. The use of stromal cell derived growth factor 1 -- elastin like peptide fusion protein nanoparticles to improve chronic skin wounds. Retrieved from https://doi.org/doi:10.7282/T3D50Q5G

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TitleThe use of stromal cell derived growth factor 1 -- elastin like peptide fusion protein nanoparticles to improve chronic skin wounds
NameYeboah, Agnes (author); Yarmush, Martin l (chair); Rutgers University; Graduate School - New Brunswick
Date Created2016
Other Date2016-05 (degree)
SubjectChemical and Biochemical Engineering, Skin--Wounds and injuries
Extent1 online resource (xvi, 116 p. : ill.)
DescriptionChronic 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.
NotePh.D.
NoteIncludes bibliographical references
Noteby Agnes Yeboah
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3D50Q5G
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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