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Title: Control of biological responses by isolated synthetic material variables
Author: Lee, I.
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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It is well established that cells sense and respond to stimuli at the sub-micron and nanometre scale, a factor that must be considered in future biomaterial design. The understanding of how biological entities interact with material features at this scale is limited due to the limitations of material fabrication techniques that can readily isolate enrichment of a surface with a chemical group, whilst reproducibly controlling nanotopography and stiffness. Polymer pen lithography (PPL), a nanotechnology that has advanced the technique of single probe nanolithography in combination with traditional microcontact printing, has since been introduced due to its capability of fabricating high throughput surface patterns over large surface areas (multiple cm2) in a short period of time. In this work, PPL has been used as a powerful nanotechnique to fabricate reproducible surface nanofeatures with a size of 300 nm with various centre-to-centre distances using a range of chemicals as "inks" with presentation of pre-selected carboxyl and amino groups on appropriate surfaces as "papers". These fabricated surfaces have been used to evaluate the isolated and combitorial effects of changes in surface chemistry and topography on mesenchymal stem cell and chondrocyte adhesion and phenotype in vitro. Carboxylic acid terminated nanoarrays with various centre-to-centre distance have been proven to induce mesenchymal stem cell towards chondrogenesis and hypertrophic chondrogenesis. In addition, the selected carboxylic acid terminated nanoarrays successfully promoted the maintenance of chondrogenic phenotype of articular chondrocytes over 3 experimental passages. Conversely, amino terminated nanoarrays with various centre-to-centre distance potentially supported mesenchymal stem cell differentiation towards adipogenesis. In addition to understanding the role of surface chemistry on initial cell response, the in situ control of stiffness at a molecular level has been studied. A range of photoresponsive molecules were synthesised and incorporated within the hydrogel network. Preliminary cell-surface interactions were established with these hydrogels. The developed nanofabrication methodology and established parameters exhibited unprecedented control of cell morphology, differentiation and maintenance of phenotypes that has improved the fundamental understanding of mechanical signalling events.
Supervisor: Curran, Jude ; Rhodes, Nick ; Hunt, John ; Wong, Lu Shin Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral