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Keratin Biomaterial Treatments For Burn Injury And Mechanisms Of Tissue Survival

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abstract
Thermal burns typically display an injury pattern dictated by the transfer of the thermal energy into the skin and underlying tissues. There are often three zones of injury represented by a necrotic zone of disrupted cells and tissue, an intermediate zone of injured and dying cells, and a distant zone of stressed cells that will recover with proper treatment. There are currently no approved clinical therapies that target the zone of stasis and can reduce the need for excision and grafting by salvaging potentially viable cells and tissue and thereby contributing to spontaneous healing. In this project, we endeavored to investigate the potential of keratin biomaterials to mediate such healing. Pilot studies testing treatment of chemical (mouse model) and thermal (swine model) burns showed that a native mixture (termed "crude keratose" throughout this thesis) of keratose was able to promote wound healing by stabilizing the size of the burn, suggesting that cell survival was being facilitated in the zone of stasis. These results led us to hypothesize that the interaction of the keratose biomaterial with cells and tissue promoted survival and reduced the total body surface area burned. As crude keratose is a heterogeneous mixture of proteins representing alpha and gamma protein fractions, we determined the differential activity on cell survival associated with these fractions by using an in vitro thermal stress model and showed that gamma keratose contributed to cell survival while alpha keratose did not. In additional studies, the specific mechanism of cell survival associated with the gamma keratose fraction was investigated. These results showed that gamma keratose was able to down regulate the genes involved in cell death pathways. Later, an in vivo porcine deep partial thickness burn model was developed to study the wound healing properties of a modified keratose hydrogel (MKH) that contained a reduced amount of gamma keratose, reflecting the same concentrations used in in vitro thermal stress model. The MKH showed a faster re-epithelialization rate and wound closure compared to other treatments. Finally, to investigate the potential clinical relevance to actual burn treatment, a delayed treatment thermal burn study was performed. These results showed that MKH was able to promote faster wound healing compared to other treatments but not with the same efficacy compared to more immediate post-burn treatment. This work suggested the potential benefit of using keratin biomaterial in burn therapy and provided informative data for developing second generation keratin biomaterial treatments.
subject
Apoptosis
Autophagy
Deep partial thickness burn
Keratose
Polyethyleneglycol
Pre-clinical Study
contributor
Poranki, Deepika (author)
Van Dyke, Mark E (committee chair)
Tytell, Michael (committee member)
Lively, Mark O (committee member)
Molnar, Joseph (committee member)
Willingham, Mark (committee member)
date
2012-09-05T08:35:17Z (accessioned)
2012-09-05T08:35:17Z (available)
2012 (issued)
degree
Molecular Genetics & Genomics (discipline)
identifier
http://hdl.handle.net/10339/37431 (uri)
language
en (iso)
publisher
Wake Forest University
title
Keratin Biomaterial Treatments For Burn Injury And Mechanisms Of Tissue Survival
type
Dissertation

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