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Development of poly(vinylpyrrolidinone) newtorks for treatment of skin graft contracture.

Smith , Louise Elizabeth (2008) Development of poly(vinylpyrrolidinone) newtorks for treatment of skin graft contracture. PhD thesis, University of Sheffield.

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Skin graft contracture is a problem facing many bums patients treated with skin grafts. Currently grafts under suspicion of contraction are treated with pressure garments to prevent contractures progressing. Patients may have to wear these for many months however once contractures have formed surgical intervention is commonly required. The aim of this project was to develop a hydrogel drug delivery system to prevent or reduce skin graft contracture. Two potential anti-contraction agents, identified based on prior work from our laboratory were initially examined for their effectiveness in preventing contracture formation using two 3D models of contraction - collagen I gels and a reconstructed human skin model. 13-aminopropionitrile (13APN), a noncompetitive lysyl oxidase inhibitor significantly reduced contraction in the reconstructed skin model but not the collagen gel model while 4-methyl umbelliferone (4-MU) reduced contraction in both models. For hydrogel drug delivery poly(N-vinylpyrrolidinone) (PNVP) hydrogels were developed with material properties suitable for use as a non-cytotoxic wound dressing. Two crosslinked PNVP's were investigated, one crosslinked with ethylene glycol dimethacrylate (EGDMA) and the other crosslinked with diethyleneglycol bis allylcarbonate (DEGBAC). The different crosslinkers led to hydrogels with different mechanical and slightly different biological properties. Although neither hydrogel proved to be suitable for culturing cells on, indirect contact with both showed them to be biocompatible and in some cases stimulatory to fibroblasts. These hydrogels were evaluated for their uptake and release of 13APN and 4-MU. Hydrogels were then used to deliver 13APN and 4-MU to reduce skin cell contraction in both collagen gels and the reconstructed skin model with some promising preliminary results showing hydrogels releasing 4-MU to reduce contraction in the 3D collagen gel model.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Materials Science and Engineering (Sheffield)
Identification Number/EthosID: uk.bl.ethos.490185
Depositing User: EThOS Import Sheffield
Date Deposited: 02 Nov 2016 09:39
Last Modified: 02 Nov 2016 09:39
URI: http://etheses.whiterose.ac.uk/id/eprint/15157

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