Show simple item record

dc.contributor.advisorShipston, Michael
dc.contributor.advisorIredale, John
dc.contributor.advisorMurray, Alan
dc.contributor.authorHughes, Mark Antony
dc.date.accessioned2015-04-13T14:15:23Z
dc.date.available2015-04-13T14:15:23Z
dc.date.issued2014-11-28
dc.identifier.urihttp://hdl.handle.net/1842/10029
dc.description.abstractCell patterning platforms support diverse research goals including tissue engineering, the study of cell physiology, and the development of biosensors. Patterning and interfacing with neurons is a particular challenge, being approached via various bioengineering approaches. Such constructs, when optimised, can inform our understanding of neuronal computation and learning, and ultimately aid the development of intelligent neuroprostheses. A fundamental pre-requisite is the ability to dictate the spatial organization and topography of patterned neuronal cells. This thesis details efforts to pattern neurons using photolithographically defined arrays of the polymer parylene-C, printed upon oxidised silicon wafers. Initial work focused on exploring the parylene-C:SiO2 construct as a wide-ranging cell-patterning platform, assessing cell adhesion from both substrate- and cell-centric perspectives. Next, the LUHMES (Lund Human Mesencephalic) cell line was used to explore the potential for construction of interrogatable, topographically-defined neuronal networks. In isolation, LUHMES neurons failed to pattern and did not show any morphological signs of cellular differentiation. However, in the context of a cellular template (the HEK 293 cell line which was found to pattern reliably), LUHMES were able to adhere secondarily on-chip. This co-culture environment promoted morphological differentiation of neurons. As such, HEK 293 cells fulfilled a role analogous to glia, dictating neuronal cell adhesion and generating an environment conducive to neuronal survival. Neurites extended between islands of adherent cell somata. The geometry and configuration of parylene-C influenced the organisation of neurites. With appropriate designs, orthogonal neuronal networks could be created. The dominant guidance cue for neurite growth direction appears to be a diffusible chemotactic agent. HEK 293 cells were later replaced with slower growing human glioma-derived precursors, extracted during tumour debulking surgery. These primary cells patterned accurately on parylene-C and provided a similarly effective, and longer lasting, scaffold for neuronal adhesion.en
dc.contributor.sponsorWellcome Trusten
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionHughes MA, Bunting A, Brennan PM, Cameron K, Murray AF & Shipston MJ. (2014) Patterning human neuronal networks on photo-lithographically engineered silicon dioxide substrates functionalized with glial analogues. J Biomed Mat Res A. 102(5): 1350-60.en
dc.relation.hasversionHughes MA, Bunting A, Brennan PM, Shipston MJ & Murray AF. (2014) Cell patterning on photolithographically-defined parylene-C/SiO2 substrates. J Vis Exp. 85: e50929, doi:10.3791/50929.en
dc.relation.hasversionHughes MA, Bunting A, Cameron K, Murray AF, & Shipston MJ. (2013) Modulating patterned adhesion and repulsion of HEK 293 cells on micro-engineered parylene-C/SiO2 substrates. J Biomed Mat Res A. 101(2): 349-57.en
dc.relation.hasversionHughes MA, Murray AF, & Shipston MJ. (2012) Progress towards merging neuronal network engineering with semiconductor microelectronics technology: tools for neuroscience and neurosurgery. Society of British Neurological Surgeons (SBNS) Annual Conference, Aberdeen. Proceedings: British Journal of Neurosurgery 2012; 26(2): 132–174.en
dc.relation.hasversionHughes MA. (2014) Engineering brain-computer interfaces: past, present and future. J Neurosurg Sci. 58(2): 117–23.en
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectneurons patterningen
dc.subjectparyleneen
dc.subjectsiliconen
dc.titleCell patterning and neuronal network engineering on parylene-C:SiO2 substratesen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


Files in this item

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-ShareAlike 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International