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Biomedical aspects of membrane chemistry

McEwan, C. E. A. (2017) Biomedical aspects of membrane chemistry. PhD thesis, University of Reading

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This thesis is focused on the development of a prototype membrane medical device for the treatment of oedema and lymphoedema via interosmolar fluid removal. These medical disorders disrupt body fluid regulation causing excess fluid to accumulate in the body’s tissues resulting in swelling of affected areas and can severely impact quality of life of affected patients. The device concept was based on a US patent (No. 8,211,053 B2) licensed to BioInteractions Ltd which proposes, but does not exemplify, an implantable medical device based on a semipermeable membrane compartment containing trapped osmotic solutes which can act as a draw solution for the abnormally accumulated fluid in the tissues surrounding the device, allowing the fluid to be drained from the body. Following extensive literature research and consultation with experts in the field (detailed in Chapter 1) it became apparent that alongside the oedema fluid, accumulated plasma proteins would also require removal to prevent oedema reforming as a result of protein oncotic pressure. To accommodate this, a design modification was proposed; employing porous membranes to enable to removal of proteins alongside the fluid. This adaptation necessarily affected the draw solution selection limiting the options to high molecular weight species which could be retained by the porous membrane. Alongside this clinically-oriented project, a secondary project involved the development of thin-film composite membranes using novel coatings based on hydrophilic poly-ylids as well as investigations into a new solvent resistant support membrane. Chapter 2 focused on investigating the forward osmosis process using a novel combination of porous ultrafiltration membranes and high molecular weight polymer and polyelectrolyte draw solutions. The best-performing draw solution and membrane was found to be 225K sodium polyacrylate and a 50K MWCO polyethersulfone (PES) UF membrane which were then further studied to determine model oedema fluid removal performance, membrane fouling properties, osmotic pressure characteristics and protein transport. Chapter 3 involved the synthesis and characterisation of novel hydrophilic poly-ylids derived from the interfacial polycondensation of 1,1’-diamino-4,4’-bipyridinium with aromatic di-sulfonyl chlorides and di-isocyanates. These poly-ylids were then used to fabricate thin-film composite nanofiltration membranes, alongside a number of previously reported acid chloride based poly-ylids for comparison, which were then analysed in terms of their flux and salt rejection properties. Additionally investigations into pH effects, surface morphology and biocompatibility were carried out. Chapter 4 describes the development of solvent resistant thin-film composite membranes based on poly-ylids synthesised in Chapter 3, in combination with a novel polyetherketone support membranes. This system enabled the fabrication of nanofiltration membranes using monomers that were incompatible with a traditional PES membrane support. The membranes were analysed as described in Chapter 3 and were found to have reasonable flux and salt rejection properties. Additionally, initial biocompatibility testing found that all three PEK TFC poly-ylid membranes were able to reduce protein adhesion relative to an uncoated PEK support membrane. Chapter 5 details the design, fabrication and testing of two generations of device prototypes using both an in vitro and ex vivo model, both developed specifically for the project. This chapter provides proof-of-concept for the device, as fluid removal was successfully demonstrated using a second generation prototype tested in an ex vivo perfused limb.

Item Type:Thesis (PhD)
Thesis Supervisor:Colquhoun, H. M. and Hayes, W.
Thesis/Report Department:School of Chemistry, Food and Pharmacy
Identification Number/DOI:
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
ID Code:75915


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