McCarthy, Emma Morgan (2020). The external manipulation of collagen type I using inorganic ions and topographical cues. University of Birmingham. Ph.D.
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McCarthy2020PhD.pdf
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Abstract
Collagen is a crucial component of tissue. It is a main protein of the extracellular matrix and functions as a cellular support, aiding cell-matrix signalling. As it supports cells, its orientation and structure are highly important; any alterations in collagen formation and assembly cause an alteration in tissue type. Collagen is a hierarchical protein, forming intercellularly before being released into the extracellular matrix where collagen molecules self-assemble. The simplest form of collagen is a triple helix, with a repeating amino acid structure predominately made of Gly-X-Y (where X and Y are usually proline and hydroxyproline respectively). This triple helix forms the collagen molecule, which self-assembles and super twists into microfibrils, fibrils and then fibres within the extracellular space. As there are many stages to collagen formation, it can be externally manipulated at many points to produce changes to the overall matrix structure and function. Within this thesis, the influence of inorganic ions and surface topography are investigated within the context of exploring how metal-on-metal implants effect collagen matrix formation, the fundamentals of how early stage collagen mineralisation occurs and how collagen fibrils' alignment can be influenced for wound dressings. It was found that cobalt ions, a main constituent of metal-on-metal implants are detrimental to matrix assembly. It was also found that calcium and phosphate (two of the main components of bone mineral) individually cause a conformational change in the molecular structure of collagen, ultimately preventing fibril formation to occur, but together allow for native fibril assembly. Although introducing chemicals into the collagen environment resulted in a drastic change in assembly, altering the surface chemistry did not. However, surface topography plays a large part in collagen alignment, with a nano-pattern of ridge to gap ratio 1.5 and a depth of 1000 nm resulting in 60% collagen alignment perpendicular to the ridge edge. The results within this thesis show that when creating a medical device, or wound dressing, it is important to factor in any changes to the extracellular matrix as they fundamentally control cellular function through support and facilitation of cell signalling. Therefore, by investigating how to externally manipulate collagen, better ways to treat trauma, such as scarring, and a better understanding of how devices, such as implants, can influence the surrounding tissue can be understood.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||||||||
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| Licence: | All rights reserved | |||||||||||||||
| College/Faculty: | Colleges (2008 onwards) > College of Engineering & Physical Sciences | |||||||||||||||
| School or Department: | School of Chemistry | |||||||||||||||
| Funders: | Engineering and Physical Sciences Research Council, National Institute for Health Research | |||||||||||||||
| Subjects: | Q Science > Q Science (General) | |||||||||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/10291 |
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