Stubbs, Christopher D. (2019) Synthetic macromolecules for cryopreservation and cell storage. PhD thesis, University of Warwick.

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Abstract

The transport and storage of mammalian cells is a significant technical challenge that is currently limiting the adoption of a range of cell-based technologies. Cryopreservation is an attractive method to enable the long-term storage of cells and tissues, however the necessary freezing and thawing processes cause extensive cell damage and therefore cryoprotectants are required to inhibit the mechanical and osmotic damage caused by ice growth (recrystallisation). Antifreeze proteins, used by plants, animals and bacteria to survive low temperature environments were initially considered to solve these problems, however their complex synthesis, and dynamic ice shaping limit their usefulness. As a result of these limitations, synthetic cryoprotectants are of great interest. The most potent synthetic ice recrystallisation inhibitor (IRI) currently known is poly(vinyl alcohol), and therefore Chapter 2 details attempts to further understand its mechanism of action, by investigating the effect of a series of modifications on its IRI activity. Chapter 3 explores the effect of regioregularity and hydrophobicity on poly(ampholyte) IRI activity, then uses the design rules observed to generate a highly active, scalable, cryoprotectant. Chapter 4 details the development of a high throughput photoiniferter polymerisation, as well as the limitations of the technique. This process, paired with a high throughput cryopreservation assay, is then used to screen a library of 120 poly(ampholyte) terpolymers. Chapter 5 investigates the effect of hydrophobic modification on an IRI inactive, fully flexible polymer, in order to determine whether IRI activity can be induced by simple polymer modification.

In summary, a number of polymeric materials are synthesised to probe the relationship between structure and function of a number of IRI active, and inactive, materials. The relationship between IRI activity and cryoprotectant activity is then investigated using a number of poly(ampholytes), observing that for some materials, IRI activity does not necessarily correlate with cryoprotectant activity.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology T Technology > TP Chemical technology
Library of Congress Subject Headings (LCSH):	Cells -- Cryopreservation, Polyvinyl alcohol, Polyampholytes
Official Date:	June 2019
Dates:	Date Event June 2019 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Gibson, Matthew I.
Sponsors:	European Research Council
Format of File:	pdf
Extent:	xxxvi, 292 leaves : illustrations (some colour)
Language:	eng

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