An increase in degenerative bone disease in an ageing population, combined with a rise in the number of patients suffering from bone defects caused by physical trauma, makes the repair of bone an issue of growing clinical relevance. Current treatments such as autografts and allografts have major drawbacks, including donor site morbidity, limited availability, disease transmission and immune rejection. To overcome these issues synthetic bone grafts have been developed to mimic the mineral phase of bone. Given the significant roles of silicon in bone growth and development there has been great interest in introducing silicon into synthetic bone grafts to enhance their bioactivity. Calcium phosphate based silicate containing grafts have demonstrated enhanced bioactivity, improved physical properties, enhanced protein adsorption and greater bone formation, when compared to non-silicated calcium phosphates such as hydroxyapatite. However, is not clear whether the increased bone formation associated with these materials is the result of greater osteoblast activity or a rise in numbers of osteoblasts resulting from activation and differentiation of stem/ progenitor cells. To answer this question, multipotent stem cells were cultured on silicate substituted calcium phosphate (Si-CaP) and hydroxyapatite (HA). Si-CaP promoted greater cell adhesion and enhanced proliferation when compared to HA. Cells differentiated along the osteogenic lineage on both substrates as evidenced by up regulation of osteoblast specific genes and proteins. However, cells on Si-CaP showed earlier and greater gene expression of all osteoblast genes examined, and greater protein production as detected by immunohistochemistry. Integrin gene expression analysis revealed up regulation of α an d β subunits on both substrates during differentiation. Integrins α5 and β1 expression were greater on Si-CaP than on HA, suggesting preferential binding of fibronectin. The implication of these findings for tissue engineering is clear, suggesting these substrates may be utilized to control stem cell fate in vivo and in vitro without the need for osteogenic supplementation. Furthermore, the increased rate of differentiation seen on Si-CaP may enable the development of novel substrates for osteogenic differentiation of MSC, which may have significant impact in regenerative medicine.

No description available.

Coronary artery bypass graft (CABG) surgery is a common treatment for patients with coronary artery disease. A potential complication of CABG is myocardial ischemia or infarction. In this thesis, a method - based on laser Doppler flowmetry (LDF) - for detection of intra- and postoperative ischemia by myocardial perfusion monitoring is evaluated. LDF is sensitive to motion artifacts. In previous studies, a method for reduction of motion artifacts when measuring on the beating heart has been developed. By using the ECG as a reference, the perfusion signal is measured in intervals during the cardiac cycle where the cardiac motion is at a minimum, thus minimizing the artifacts in the perfusion signal. The aim of this thesis was to investigate the possibilities to use the ECG-triggered laser Doppler system for continuous monitoring of myocardial perfusion in humans during and after CABG surgery. Two studies were performed. In the first study, changes in myocardial perfusion during CABG surgery were investigated (n = 13), while the second study focused on postoperative measurements (n = 13). In addition, an ECG-triggering method was implemented and evaluated. It was found that the large variations in myocardial perfusion during CABG surgery could be monitored with the ECG-triggered laser Doppler system. Furthermore, a perfusion signal of good quality could be registered postoperatively from the closed chest in ten out of thirteen patients. In eight out of ten patients, a proper signal was obtained also the following morning, i.e., about 20 hours after probe insertion. The results show that respiration and blood pressure can have an influence on the perfusion signal. In conclusion, the results indicate that the method is able to detect fluctuations in myocardial perfusion under favourable circumstances. However, high heart rate, abnormal cardiac motion, improper probe attachment and limitations in the ECG-triggering method may result in variations in the perfusion signal that are not related to tissue perfusion. / Varje år utförs omkring 4500 kranskärlsoperationer i Sverige. En allvarlig komplikation som kan uppstå efter operationen är otillräcklig blodförsörjning till hjärtmuskeln. Den här licentiatavhandlingen handlar om utveckling och utvärdering av en metod, baserad på laserdopplerteknik, för att kunna upptäcka nedsatt blodperfusion i hjärtmuskeln på ett tidigt stadium. Laserdopplertekniken är känslig för rörelsestörningar. I tidigare studier har en metod för reducering av rörelsestörningar vid mätning på slående hjärta tagits fram. Med EKG:t som referens mäts blodperfusionen i de faser under hjärtcykeln då hjärtats rörelse är som minst, vilket minskar bidraget av rörelsestörningar i blodperfusionssignalen. I den här avhandlingen undersöks om metoden kan användas för kontinuerlig övervakning av hjärtmuskelns blodperfusion på patienter under och efter hjärtoperationer. Två studier har genomförts: en där hjärtmuskelns perfusion mättes i olika faser under kranskärlsoperationer och en där mätproben lades in i hjärtmuskeln under operationen och mätningar gjordes under det första dygnet efter operationen. Det visade sig vara möjligt att följa förändringar i hjärtmuskelns blodperfusion under operation. Det var även möjligt att registrera en perfusionssignal av god kvalitet efter operationen då bröstkorgen var stängd. Hos åtta av tio patienter erhölls en bra signal även morgonen efter operationen, dvs. ca 20 timmar efter att proben lades in. Resultaten visar också att andning och blodtryck kan ha en påverkan på blodperfusionssignalen. Slutsatsen av arbetet är att det går att se variationer i hjärtmuskelns blodperfusion med EKG-triggad laserdoppler under vissa förutsättningar. Signalen är dock i många fall svårtolkad på grund av att t ex hög hjärtfrekvens, onormal hjärtväggsrörelse eller ändrad probposition sannolikt kan ge variationer i perfusionssignalen som inte är relaterade till blodflödesförändringar. / Report code: LIU-TEK-LIC-2007:35.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2006. / Polyurethanes (PUs) are finding increasing application and use in many industries due to their advantageous properties, such as a wide range of flexibility combined with toughness, high chemical resistance, excellent weatherability, and very low temperature cure. PUs do however have some disadvantages, for instance, PU is considered an expensive polymer, especially when considered for solvent based adhesives. A motivation for this study was to consider a largely unstudied area of PU chemistry by combining PUs with polyacrylates. Polyacrylates are well known adhesives and can carry specific functionality, but have the disadvantage that their flexible backbones impart limited thermal stability and mechanical strength. In this study PU was incorporated into acrylates in an effort to obtain acrylate-g-urethanes with good properties. The mode of incorporation chosen was urethane macromonomers (UMs), a hardly mentioned substance in literature, yet one deserving investigation. UMs having different urethane chain lengths (X) were synthesized by the polyaddition polymerization of toluene diisocyanate (TDI) and ethylene glycol (EG) by the prepolymer method, which was terminated by 2-hydroxy ethyl methacrylate (HEMA) and isopropanol. The UMs were characterized by Fourier-transform infrared spectroscopy (FTIR), proton NMR (1H NMR), carbon NMR (13C NMR), gel permeation chromatography (GPC), thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA). Various percentages of the respective UMs (0-40 wt % according to acrylate monomers) were then incorporated into methyl methacrylate (MMA) and into normal butyl methacrylate (n-BMA) backbones via solution free radical copolymerization. The resulting methyl methacrylate-urethane graft copolymers (PMMA-g-urethane) and normal butyl methacrylate-urethane graft copolymers (n-PBMA-g-urethane) were characterized by GPC, 1H NMR and 13C NMR, FTIR, TGA, and DMA. Phase separation between the urethane segment and acrylate segment in the yield of graft copolymerization products was investigated by DMA and transmission electron microscopy (TEM). As the concentration of the UMs in the free radical copolymerization feed increased, lower yields of both graft copolymers PMMA-g-urethane and n-PBMA-g-urethane were observed and more UM was incorporated into the PMMA and n-PBMA backbones. It also was found that the thermal stability of the PMMA-g-urethane and n-PBMA-gurethane copolymers increased with increasing UM concentration. DMA results showed that in most graft copolymer products the two respective component parts of PMMA-g-urethane or n-PBMA-g-urethane were completely compatible as only one Tg was observed. Two glass transitions, at temperatures of 22.0 and 76.0 oC, corresponding to the n-PBMA and urethane moieties, were observed when the chain length of the UMs was increased from X=4 to X=32 [the amount of this UM used in the copolymerization feed was increased to 40%, and microphase separation was indicated].

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2006. / Synthesis of a series of poly (methylmethacrylate)-graft-poly (styrene) polymer was carried out via free radical polymerization of methylmethacrylate and polystyrene macromonomers. The macromonomers were synthesized via living anionic polymerization techniques. Two series of macromonomers where synthesized with different polymerizable end group functionalities, by termination with p-vinyl benzyl chloride and 3-(dimethyl chloro silyl) propyl methacrylate. The branch density was varied by controlling the composition feed ratio of the macromonomers to comonomer. Liquid chromatographic techniques were used to fully characterize the chemical composition and branch distributions of the graft polymer. Liquid chromatography under critical conditions of adsorption of styrene coupling with Fourier Transform Infrared Spectra was used to investigate the chemical composition and distribution of the branches in the graft. Physical properties of the graft copolymers such as Tg and free volume were determined using differential scanning calorimetry and positron lifetime spectrometry respectively. The relationship between the chemical composition and the graft copolymer properties such as Tg and free volume were investigated. The results show that for long chain macromonomers phase segregation occurs in the graft copolymers. In the case of shorter chain macromonomers at low content no phase segregation is observed and the macromonomers have an antiplasticization effect on the graft polymers.

Thesis (MSc)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: The main objective of this project was the controlled synthesis of graft copolymers via a thiol-ene addition mechanism. The Reversible Addition-Fragmentation chain Transfer (RAFT) process was used in all polymerization reactions with the aim to achieve a certain degree of control over the molecular weight. Several synthetic steps were required in order to obtain the final graft copolymer and each step was investigated in detail. Firstly, two RAFT agents (cyanovaleric acid dithiobenzoate and dodecyl isobutyric acid trithiocarbonate) were synthesized to be used in the various polymerization reactions of styrene and butyl acrylate. This was done successfully and the RAFT agents were used to synthesize low molecular weight polystyrene branches of the graft copolymer. Different molecular weights were targeted. It was found that some retardation phenomena were present especially at high RAFT agent concentrations. The polystyrene branches that were synthesized contained RAFT end-groups. Various pathways were explored to modify these RAFT end-groups to form thiol end-groups to be used in the thiol-ene addition reaction during the grafting process. The use of sodium methoxide for this purpose proved most successful and no evidence of the formation of disulfide bridges due to the initially formed thiols was detected. Allyl methacrylate (AMA) was chosen as monomer to be used for the synthesis of the polymer backbone because it has two double bonds with different reactivities. For the first time, RAFT was used to polymerize AMA via the more reactive double bond to obtain linear poly(allyl methacrylate) (PAMA) chains with pendant double bonds. However, at higher conversions, gelation occurred and the molecular weight distributions were uncontrolled. NMR was successfully used to study the tacticity parameters of the final polymer. Finally, the synthesis of the graft copolymer, PAMA-g-polystyrene, was carried out by means of the “grafting onto” approach. The thiol-functionalized polystyrene branches were covalently attached to the pendant double bonds of the PAMA polymer backbone via a thiol-ene addition mechanism in the presence of a free radical initiator. A Multi- Angle Laser Light Scattering (MALLS) detector was utilized in conjunction with Size- Exclusion Chromatography (SEC) to obtain molecular weight data of the graft copolymer. The percentage grafting, as determined by 1H-NMR, was low. / AFRIKAANSE OPSOMMING: Die hoofdoel van hierdie projek is die beheerde sintese van ‘n entkopolimeer via ‘n merkaptaan-een addisiereaksie. Die sogenaamde “Reversible Addition-Fragmentation chain Transfer” (RAFT) proses is in al die polimerisasiereaksies gebruik met die doel om ‘n mate van beheer oor die molekulêre massa van die polimere te verkry. Verskeie stappe (waarvan elkeen ten volle ondersoek is) was nodig om die finale entkopolimeer te verkry. Eerstens is twee RAFT-agente (sianovaleriaansuur ditiobensoaat en dodekielisobottersuur tritiokarbonaat) gesintetiseer vir gebruik in verskeie polimerisasiereaksies van stireen en butielakrilaat. Hierdie stap was suksesvol en die RAFT-agente is toe gebruik vir die sintese van lae molekulêre massa polistireensytakke vir die entkopolimeer. Die molekulêre massas van die sytakke is gevarieer en daar is gevind dat vertragings in die polimerisasiereaksies voorgekom het, veral by hoë konsentrasies van die RAFT-agente. Die polistireensytakke wat gemaak is, besit almal ‘n RAFT-eindgroep. Verskeie roetes is bestudeer ten einde die RAFT-eindgroepe tot merkaptaan-eindgroepe te modifiseer om sodoende tydens ‘n merkaptaan-een addisiereaksie gebruik te word. Die gebruik van natriummetoksied was hier die suksesvolste en daar was geen teken van die vorming van disulfiedbrûe as gevolg van die oorspronklik gevormde merkaptane nie. Allielmetakrilaat (AMA) is gekies as die monomeer wat gebruik sou word vir die sintese van die polimeerruggraat omdat die monomeer twee dubbelbindings met verskillende reaktiwiteite besit het. Vir die eerste keer is RAFT gebruik vir die polimerisasie van AMA via die meer reaktiewe dubbelbinding om lineêre poli(allielmetakrilaat) (PAMA) kettings met dubbelbindings in die sygroepe te verkry. Gelvorming en onbeheerde molekulêre massaverspreiding het egter by hoër monomeeromsettings voorgekom. KMR is susksekvol gebruik om die taktisiteitsparameters van die finale polimeer te bestudeer. Ten slotte is die sintese van die entkopolimeer, PAMA-g-polistireen, uitgevoer deur die aanhegting van voorafgevormde sytakke. Die polistireensytakke met die merkaptaaneindgroepe is kovalent geheg aan die dubbelbindings in die sygroepe van die PAMA-polimeerruggraat via ‘n merkaptaan-een addisiemeganisme in die teenwoordigheid van ‘n vrye radikaalinisieerder. ‘n Kombinasie van gelpermeasiechromatografie en multi-hoeklaserligverstrooiing is gebruik om die molekulêre massa van die entkopolimeer te bepaal. Die persentasie sytakke soos bepaal deur 1H-KMR was laag.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2007. / Hybrid graft copolymers of polydimethylsiloxane (PDMS) and polymethylmethacrylate (PMMA) were synthesised. PDMS macromonomers were synthesised anionically from the cyclic D3 monomer. This living polymerisation was terminated with a [3- (methacryloxy)propyl]-dimethylchlorosilane terminating agent which resulted in the functionalised macromonomer. These PDMS macromonomers and MMA monomer were copolymerised to form PMMA-g-PDMS hybrid copolymers by conventional free radical reactions. Synthesised and commercial methacryloxy-functionalised PDMS macromonomers having a range of molar masses were copolymerised with MMA to form graft copolymers of various chemical compositions. PDMS content in the graft copolymers could be varied by the amount of PDMS incorporated into the copolymer as well as by varying the length of the PDMS side chains. Size exclusion chromatography (SEC) results confirmed low PDI’s for the PDMS macromonomers synthesised anionically. NMR studies allowed characterisation of the synthesised PDMS macromonomers and PMMA-g-PDMS copolymers. It also allowed the determination of relative ratios of PMMA:PDMS in the graft copolymers. Gradient elution chromatography (GEC) was used successfully to monitor the presence and removal of the PDMS macromonomer from the graft copolymer products. The influence of PDMS content of the graft copolymers on retention time was also evaluated using this technique. Two dimensional chromatography confirmed the formation of PMMA-g-PDMS copolymer as well as PMMA homopolymer during some of the grafting reactions. GEC in the first dimension was coupled to SEC in the second dimension. PAS-FTIR studies allowed chemical characterisation of the graft copolymer and confirmed surface segregation of the PDMS. Atomic force microscopy (AFM) was also used to study the surface segregation of PDMS and looked at the relationship between surface polarity and increasing PDMS content. The study showed the effect of thermal treatment on the surface morphology of the hybrid polymers. Corona treatment was used to modify the surface structure of the graft copolymer films. Contact angle studies provided evidence of hydrophobic loss and recovery after corona for the hybrid polymer materials containing PDMS. This is one of the first reported examples of hydrophobicity recovery in these types of hybrid materials after corona treatment. Slow positron beam studies highlighted the formation of a thin silica like layer on the surface of the films after corona similar to that observed for pure cross-linked PDMS compounds. The positron studies enabled estimation of the thickness of the silica like layer.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2006. / Cellulose, one of the most abundant organic substances on earth, is a linear polymer of D-glucose units joined through 1,4-β-linkages. Cellulose is however not easily processed without chemical modification. A number of techniques exist for the modification of cellulose, of which the viscose process is one of the most widely applied. Grafting of synthetic polymeric chains onto or from cellulosic materials is an useful technique that can be used to combine the strengths of synthetic and natural polymers dramatically, so changing the properties of cellulosic materials (pulp, regenerated cellulose, cellulose derivatives). In this study five model xanthate (Reversible Addition-Fragmentation chain Transfer (RAFT)/Macromolecular Design through Interchange of Xanthates (MADIX)) agents, namely, monofunctional, difunctional, trifunctional and tetrafunctional species of the form S=C(O-Z)-S-R, with different leaving groups and different activating moieties, were prepared and then studied to determine the feasibility of cellulose modification via addition fragmentation processes. These agents were characterized by Nuclear Magnetic Resonance spectroscopy (NMR), Fourier Transform Infrared spectroscopy (FT-IR) and Ultraviolet spectroscopy (UV). Polyvinyl acetates (PVAc) in the form of linear, three armed and four armed star shaped polymers were then successfully synthesized in reactions mediated by these xanthate RAFT/MADIX agents Xanthates were applied to polysaccharide materials using the viscose process (xanthate esters were formed directly on a cellulosic substrate, with subsequent alkylation) Grafting reactions were then conducted with the polysaccharides; cellulose was modified with vinyl acetate, [this is an example of a surface modification of natural polymers that is of interest in various industries, such as textiles and paper manufacture]. Analysis of the graft copolymers was conducted via Size Exclusion Chromatography (SEC), Liquid Adsorption Chromatography (LAC), Thermogravimetric Analysis (TGA), and FT-IR. Polyvinyl acetate was successfully grafted onto three polysaccharides (cellulosic materials), namely Hydroxyl Propyl Cellulose (HPC), Methyl Cellulose (MC) and cellulose. The study showed that the modification of cellulosic substrates with defined grafts of vinyl acetate can be easily achieved through minor modifications to existing industrial techniques.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2006. / Graft and block copolymers were synthesized using multifunctional and monofunctional macroinitiators to produce the copolymers. The process involved hydroboration of commercially available unsaturated rubbers and chain-end unsaturated macromonomers with 9-borabicyclo [3.3.1] nonane (9-BBN). The resulting secondary alkyl 9-BBN moieties in the starting materials were subsequently exposed to oxygen in the presence of free radical polymerizable monomers to facilitate the formation of graft and block copolymers. This research was initiated by first studying the hydroboration of a model compound, 2-hexene, in order to determine the optimal conditions for the graft reactions. The model compound was subsequently used as a macroinitiator to initiate the polymerization of methylmethacrylate (MMA). The same borane chemistry was extended to the synthesis of polystyrene (PS) block copolymers. Chain-end unsaturated PS macromonomers, synthesized by anionic polymerization, were effectively hydroborated and then polymerized to produce PS-b-PMMA block copolymers. The synthesis of polyolefin graft copolymers was subsequently achieved by hydroboration. Several commercial rubbers with different levels of unsaturated segments were efficiently grafted with vinyl monomers MMA and styrene (St) following the “graft from” approach. The grafted reactions were carried out under various reaction conditions to determine the effect of the following factors: concentration of oxygen, amount of borane and monomer concentration. By controlling these factors, different graft densities were achieved with high graft efficiencies. All reactions produced mixed products including unreacted (non-functional) macroinitiator, homopolymer, graft copolymer and in case of the highly unsaturated polymer a crosslinked gel. Finally, the chemical compositions as well as the molar mass distribution of the graft copolymers were fully characterized by different chromatographic techniques. 1H-NMR and FTIR were also used to confirm the structure of these copolymers. Gradient HPLC was developed and extensively used to characterize the graft copolymers.

Thesis (PhD (Chemistry and Polymer Science))--Stellenbosch University, 2008. / Polysaccharides were modified with selected polymers via the grafting technique. Both anionic and cationic polysaccharides were prepared. Random and crosslinked graft copolymers were also prepared. The percentage grafting was determined by gravimetric analysis and results were confirmed by cross-polarization magic angle spinning carbon-13 nuclear magnetic resonance microscopy (CP/MAS 13C NMR). These modified biodegradable polymers were then used to flocculate precipitated calcium carbonate (PCC). The effects of pH, percentage grafting, crosslinker concentration and polysaccharide concentration on PCC flocculation were evaluated. Furthermore, the effects of anionic and cationic starch, either added to PCC sequentially or simultaneously, on PCC flocculation were also investigated. Generally, anionically modified starch showed excellent flocculation properties, which are desirable for the end application of PCC retention. The effect of polyacrylic acid (PAA) and polyacrylamide (PAM) modified cellulose fibers on calcium carbonate crystal nucleation and growth modification was investigated. When the heterogeneous crystallization of CaCO3 was carried out in the presence of modified cellulose fibers the CaCO3 crystals were found to be residing on the surface of the fibers. The morphologies of the crystallized CaCO3, polymorph and fiber surface coverage were different for cellulose materials grafted with polymers of different functionalities, meaning that there is interaction between the crystal growth modifier and the growing nuclei. The effect of the modified starch on the crystallization of calcium carbonate gave useful insight into designing CaCO3 filler morphologies. It was found that the filler size, morphology and surface properties of fillers can be tailor-made by choosing suitable CaCO3 crystallization conditions as well as a suitable crystal growth modifier. The crystallized CaCO3 had a negatively charged surface. Results of fluorescence studies showed that the PAA modified starch (polymeric additive used) resided on the surface of the crystals. Thus the presence of the polysaccharide on the surface of a filler could be advantageous for strengthening fiber–filler bonding in paper applications. Anionic starch materials were also used to prepare anionic-starch-coated starch particles. Both the anionic starch and anionic-starch-coated starch particles were evaluated for PCC retention and other properties of hand sheets. When anionic-starch-coated starch particles were used there was generally an improvement in the PCC retention, while the other paper properties remained desirable. The success achieved with the use of anionic-starch-coated starch particles now opens the way for the further preparation and testing of various modified starch particles, for optimization of filler retention.