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Tissue engineering offers a potential alternative therapy to overcome the limitations of organ transplantation, by employing biomaterials as scaffold for cell growth. For example, poly-lactic-co-glycolic acid (PLGA) is a synthetic biomaterial widely used in tissue engineering. However, the hydrophobicity of PLGA results in scaffolds that are poorly wettable, and which, therefore, possess poor mass transfer properties for the delivery of nutrients and the removal of waste. The present work aimed to develop more hydrophilic PLGA scaffolds, specifically hollow fibre membranes, within a bioreactor system, which enables co-culture of cells in order to direct stem cell differentiation. Large quantities of costly growth factors are required over long periods for stem cell differentiation. Therefore, this project also aimed to use a cell line as a “factory” for the inexpensive, in situ growth factor production. Hollow fibres were fabricated by wet spinning and a hydrophilic polymer, polyvinyl alcohol (PVA), was added to the PLGA solution at three different concentrations (1.25, 2.5, 5% w/w) in order to obtain a more hydrophilic membrane. Results indicated that 5% PVA-PLGA hollow fibres were the only membranes which allowed permeation of water, BSA and cell-secreted hepatocyte growth factor (HGF), thus indicating that they are the most suitable membranes for use in bioreactor devices. However, these membranes failed to improve cell-attachment. Cell secreted HGF was shown to be more stable in a dynamic culture environment than commercial HGF, thus suggesting its suitability for applications in bioreactor devices. However, using both commercial and cell-secreted HGF, mesenchymal stem cell differentiation was unsuccessful. In conclusion, this work has developed a hollow fibre membrane which is more permeable to water and proteins for a higher mass transfer of nutrients, and has realised a model system for the inexpensive production of growth factors for use in bioreactor devices and the differentiation of stem cells.

The research presented herein is concerned with the chemical modification of polysulfone towards the synthesis of a hollow fibre boronic acid fixed carrier membrane system for saccharide separation. Chapter 1 firstly introduces the area of boronic acids as chemosensors, in particular for detecting saccharides. Secondly, membrane separation techniques are discussed focussing on hollow fibre membranes and their synthesis. Chapter 2 discusses the potential of boronic acid fixed carrier hollow fibre membranes for saccharide separation. Three general routes are highlighted to achieve the desired boronic acid appended polymers: electrophilic aromatic substitution, lithiation and functional monomer polymerisation. Chapter 3 describes the various attempts at achieving the target polymer via electrophilic aromatic substitution methodology. Chapter 4 describes the various attempts at achieving the target polymer via lithiation methodology. Chapter 5 investigates the ability to create functional monomers with which functional polymers can be polymerised from. Chapter 6 describes the synthesis and characterisation of the compounds discussed in chapters 3, 4 and 5.

>Magister Scientiae - MSc / Inorganic based membranes which have a symmetric/asymmetric structure have been produced using an immersion induced phase inversion and sintering method. An organic binder solution (dope) containing yttria-stabilised zirconium (YSZ) particles is spun through a triple orifice spinneret to form a hollow fibre precursor, which is then sintered at elevated temperatures to form a ceramic support. The phase inversion process for the formation of hollow fibre membranes was studied in order to produce the best morphological structure/support for palladium based membranes. The spinning parameters, particle size, non-solvent concentration, internal coagulant as well as the calcination temperature were investigated in order to determine the optimum values. Sintering temperature was also investigated, which would yield a sponge-like structure with an optimized permeability, while retaining a smooth outer surface. The supports produced by phase inversion were characterized in terms of dimension by mercury porosimetry, compressed air permeability, Surface Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The morphology of the produced ceramic support showed either dense or porous characteristics governed by the dynamics of the phase inversion process. The particle size of YSZ was examined in order to decrease the amount of agglomerates in the spinning suspension. Zetasizer tests indicated that at 15 minutes, the ultrasonic bath effectively homogenised the YSZ particles and prohibited soft agglomerates from reforming in the spinning suspension. In this study, an increase in air gap had no noticeable effect on the finger like voids but it had a considerable effect on both the inner diameter (ID) and outer diameter (OD) of the green fibres, while an increase in bore liquid flow rate and extrusion pressure promoted viscous fingering and significant effect on the ID and OD of the fibres, respectively. There was a decrease in porosity and permeability with increasing sintering temperature, addition of water concentration in the spinning suspension and varying N-methylpyrrolidone (NMP) aqueous solution of the internal coagulant. The amount of YSZ added to the starting suspension influenced the properties of the support structure. Viscous deformation was observed for dope with lower particle loading thus resulted in the formation of cracks and defects during sintering.

Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: Polysulfone hollow-fibre membranes were fabricated via the dry-wet solution spinning technique. The objective was to demonstrate the influence of the various fabrication parameters on the diameter and mechanical properties of the hollow-fibre membranes and to optimize the spinning process by controlling these parameters with a computer control system. The effects of the operation parameters were investigated using an experimental design based on a fractional factorial method (Taguchi’s design of experiments). The parameters that were considered are the spinneret size, dope solution temperature, bore fluid temperature, coagulation bath temperature, dope extrusion rate, bore flow rate and the take-up speed. A new pilot solution spinning plant was installed and upgraded, and a computer control system, based on LabView, was developed to control, monitor and log the experimental data. The diameter of the hollow-fibres were determined using a scanning electron microscope (SEM) while the mechanical properties were measured using a tensile tester. The effects of diameter size and wall thickness of the hollow-fibres on the performance of the membranes were studied. The results showed the significance of the fabrication parameters that dominate the diameter and strength of the hollow-fibres. / AFRIKAANSE OPSOMMING: Polisulfoon holvesel membrane is met ‘n droë-nat oplossingspin proses vervaardig. Die doel hiermee was om die invloed van verskeie vervaardigingsparameters op die deursnee en meganiese eienskappe van die holvesel membrane te demonstreer asook om die spin proses te optimeer deur gerekenariseerde beheer van die aanleg. ‘n Eksperimentele ontwerp, gebaseer op ‘n gedeeltelike faktoriaal metode (Taguchi se eksperimentele ontwerp) is gebruik om die invloed van die vervaardigingsparameters te ondersoek. Die parameters wat oorweeg is, is spindop grootte, materiaal temperatuur, boorvloeistof temperatuur, stolbad temperatuur, materiaal ekstrusie tempo and opwen spoed. ‘n Nuwe oplossingspin loodsaanleg was geïnstalleer en opgegradeer en ‘n rekenaar beheerstelsel, gebaseer op LabView, is ontwikkel om die aanleg te beheer, moniteer en eksperimentele data te stoor. Die deursnee van die holvesel is gemeet met ‘n skanderingelektron mikroskoop (SEM) terwyl die meganiese eienskappe bepaal is met ‘n trektoets apparaat. Die effek van die deursnee en wanddikte van die holvesels op die werkverrigting van die membrane is ook bestudeer. Die resultate toon watter vervaardigingsparameters is beduidend vir die deursnee en sterkte van die holvesels.

This doctoral thesis is focused on design of new equipment for aeration of water surface with low depth of water column. Aeration is one of ecological preventive methods to prevent growth of cyanobacteria. Increase of dissolved oxygen content in water mass leads to support of the growth of organisms which are disadvantaged by impossibility of movement in water mass and thus also to support biodiversity. Given biodiversity has a positive effect on water quality because it avoids the outbreak of one species of aquatic organism, in particular of cyanobacteria. Designed aeration equipment uses membrane formed by hollow fibre to transport oxygen into the water. When aeration dissolution of oxygen occurs directly on the membrane surface which prevents air leak in the form of bubbles. This type of aeration has low operating costs and high efficiency of input of the oxygen into the water. Distribution in the aquatic environment is ensured by special boat. This boat is moving on the water surface and the technology is installed on the upper deck. The aeration is carried out by an aeration module situated in the water. The movement of the boat is partially ensured by autonomous control.

Yes / A mass transfer model was developed for CO2 capture from a binary gas mixture of N2/CO2 in hollow fibre membrane contactors under laminar flow conditions. The axial and radial diffusions through membrane and convection in tube and shell sides with chemical reaction were investigated. COMSOL software was used to numerically solve a system of non-linear equations with boundary conditions by use of the finite element method. Three different amine solutions of monoethanolamine (MEA), diethanolamine (DEA) and n-methyldiethanolamine (MDEA) were chosen as absorbent in lumen to consider the mass transfer rate of CO2 and compare their removal efficiency. The modelling results were compared with experimental data available in the literature and a good agreement was observed. The CFD results revealed that MEA had the best performance for CO2 removal as compared to DEA and MDEA under various operating conditions due to the different CO2 loading factor of absorbents. Furthermore, efficiency of CO2 removal was highly dependent on the absorbent concentration and its flow rate, increasing of the gas flow rate caused a reduction in gas residence time in the shell and consequently declined CO2 mass transfer. The modelling results showed the influence of the absorbent concentration on the CO2 mass transfer has improved due to availability of absorbent reactants at the gas-liquid interface.

No / Objective: To investigate the use of the National Cancer Institute's hollow fiber assay (HFA) to evaluate and prioritize novel treatment strategies for clinical trials in the Ewing's sarcoma family of tumors (ESFT). Study design: The growth and morphology of ESFT cell lines in hollow fibers (HFs) was characterized in vitro and in vivo. Reliability and reproducibility were evaluated using doxorubicin. Results: The numbers of viable cells in all 6 ESFT cell lines increased with time in vitro (0 to 96 hours). The SKES-1 and A673 cell lines grew exponentially after implantation of HFs in nude mice at subcutaneous and intraperitoneal sites. ESFT cells formed highly organized distinctive morphology within the HFs in vitro and in vivo. The number of viable ESFT cells within the HFs decreased in a time-dependent (24 to 96 hours) and dose-dependent (1 to 10 mg/kg) manner after treatment with doxorubicin in vivo. Conclusions: The HFA is a versatile short-term in vivo model that may be exploited to predict efficacy of potential anticancer agents in ESFT cells. Tumor markers and pharmacodynamic endpoints may be quantified in the pure population of ESFT cells from within the HFs.

Yes / Ruthenium compounds have been shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Pt-resistance mechanisms. Electron-deficient organoruthenium complexes are an understudied class of compounds that exhibit unusual reactivity in solution and might offer novel anticancer mechanisms of action. Here, we evaluate the in vitro and in vivo anticancer properties of the electron-deficient organoruthenium complex [(p-cymene)Ru(maleonitriledithiolate)]. This compound is found to be highly cytotoxic: 5 to 60 times more potent than cisplatin towards ovarian (A2780 and A2780cisR), colon (HCT116 p53+/+ and HCT116 p53−/−), and non-small cell lung H460 cancer cell lines. It shows no cross-resistance and is equally cytotoxic to both A2780 and A2780cisR cell lines. Furthermore, unlike cisplatin, the remarkable in vitro antiproliferative activity of this compound appears to be p53-independent. In vivo evaluation in the hollow-fibre assay across a panel of cancer cell types and subcutaneous H460 non-small cell lung cancer xenograft model hints at the activity of the complex. Although the impressive in vitro data are not fully corroborated by the in vivo follow-up, this work is the first preclinical study of electron-deficient half-sandwich complexes and highlights their promise as anticancer drug candidates. / UF150295/Royal Society; University of Bradford; Government Department of Business, Energy and Industrial Strategy; SBF003\1170/British Heart Foundation Springboard Award; AMS_/Academy of Medical Sciences/United Kingdom

No / Background: Previous studies have shown extensive vascularisation surrounding subcutaneously implanted fibres when the duration of the US National Cancer Institute (NCI) hollow fibre assay was prolonged. Materials and Methods: The feasibility of adapting the NCI assay for evaluating agents targeting the tumour vasculature was investigated in vitro and in vivo. Finally, in the optimised assay, changes in neovasculature formation around the fibres following treatment with the anti-vascular agent paclitaxel were quantified by immunohistochemistry. Results: Correlations between cell number seeded, time in culture and vascular endothelial growth factor (VEGF) secretion were seen. In vivo studies showed that transplanting single rather than 3 fibres at a site reduced inflammation, reducing the length of the fibre transplanted, as did without any significant loss in cell growth over 21 days. A statistically significant reduction in neovascularisation surrounding the fibres was seen accompanying paclitaxel treatment. Conclusion: Modifications made here to the NCI hollow fibre assay demonstrate its potential for analysing anti-tumour vasculature agents.