Over recent years there has been growing focus on the potential of tissue engineering approaches to produce functional bone tissue for clinical use. This thesis highlights the potential for using magnetic particle based techniques for tissue engineering applications. This study demonstrates that magnetic micro-- and nano scale particles are well tolerated by human osteoblasts over prolonged periods of time, and can be used to stimulate calcium signalling pathways in these cells. via the application offorces to integrin rc<:eptors and the internal cytoskeleton. Furthennore, this study demonstrates for the first time that human osteoblasts express the mechanosensitive 2PK+ channel TREK-I, and investigates the potential for using magnetic particle based techniques to directly and specifically activate this class of ion channel. A model system is reported that pennits the application of mechanical forces directly to distinct regions of the TREK-l channel structure and data is presented showing the direct activation of TREK-l channels following manipulation of magnetic p~icles targeted against the extended extracellular loop region of the channel structure. In addition initial data is presented concerning the effect of static magnetic fields and targeted magnetic particle manipulation on the bacterial mechanosensitive ion channel MscL. This thesis represents the first rejX>rts of targeted mechanical stimulation of mechanosensitive ion channels with magnetic particles. This approach has huge potential applications in the field of ion channel research, and offers for the first time a method to directly investigate the structural basis ofmechanosensitivity within ion channels. Furthennore the ability to manipulate ion channel activity without the need for phannacological drugs has huge jX>tential applications in tissue engineering and the treatment of conditions and diseases caused by ion channel dysfunction
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:423423 |
| Date | January 2005 |
| Creators | Hughes, Steven |
| Publisher | Keele University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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