Diploma thesis deals with the grafting of vinyltrimethoxysilane (VTMOS) onto poly(3–hydroxybutyrate)PHB. Subsequent characterization of the amount of grafted VTMOS and changes in the thermal properties associated with the rate of crystallization. The theoretical part deals with mechanism and the influences of grafting. In the experimental part VTMOS was grafted onto PHB without subjecting VTMOS to hydrolysis and subsequent crosslinking. By differential scanning calorimetry (DSC) and Avrami equation, the effect of grafted silane group on pure was studied. The MVR was used to compare the rheological properties of initial PHB, grafted PHB and crosslinked PHB by siloxane linkages.

This diploma thesis studied the ability of Cupriavidus malaysiensis, Delftia acidovorans and Azohydromonas lata to produce poly(3-hydroxybutyrate-co-4-hydroxybutyrate), [P(3HB-co-4HB)], by using -butyrolactone and 1,4-butanediol as carbon substrates. The objective of this work was the production and characterisation of isolated polyhydroxyalkanoates (PHA). The theoretical part deals with the basic description and classification of polyhydroxyalkanoates. Next, the biosyntheses of the most investigated PHAs were described. The practical section of the work discusses and presents the output of the cultivation of five bacterial strains selected for the production of [P(3HB-co-4HB)], namely, Cupriavidus malaysiensis (DSM 19379), Delftia acidovorans (DSM 39), Delftia acidovorans (CCM 2410), Delftia acidovorans (CCM 283) and Azohydromonas lata (CCM 4448). The effect of the modified cultivation conditions for each of the used bacteria on the PHA production yields was discussed. The produced biomass after the cultivation was characterised spectrophotometrically, gravimetrically and by gas chromatography. Polymers were isolated from the biomass by the extraction in chloroform. The isolated polymers were characterised from the viewpoint of chemical composition, molecular weight and thermal properties by using Attenuated total reflection infrared spectroscopy, Size exclusion chromatography, Differential scanning calorimetry and Thermogravimetric analysis.

Diplomová práca je zameraná na mikrovlákna na báze biopolyméru poly(3-hydroxybutyrátu) a ich využitie v medicínskych aplikáciách. Teoretická časť práce sa zaoberá štúdiom procesu tvorby vláken pomocou technológie odstredivého zvlákňovania, jeho kinetikou a faktormi ovplyvňujúcimi vznik a vlastnosti vláken. Teoretická časť sa následne orientuje na krátky prehľad biopolymérov používaných v tejto technológii, charakteristiku materiálu poly(3-hydroxybutyrátu) a taktiež prezentuje návrh potenciálnej cieľovej aplikácie daných mikrovláken. Praktická časť sa koncentruje sa prípravu mikrovláken zo spomínaného poly(3-hydroxybutyrátu). Sledované a optimalizované sú viaceré parametre vedúce k lepšej zvlákniteľnosti materiálu. Praktická časť je rozšírená o modifikáciu polymérneho roztoku prídavkom iných biopolymérov a zmäkčovadiel a prípravu mikrovláken z takto modifikovanej polymérnej zmesi. Pozornosť je venovaná taktiež optimalizácii procesných parametrov. Pripravené mikrovlákna sú následne analyzované a charakterizované viacerými metódami a vzájomne porovnávané s cieľom vyvinúť alternatívu k súčasne používaným substrátom pre rast buniek v 3D.

A PHA producing bacterium (strain QN271) was selected from mangrove soil samples collected from Quang Ninh province by using the Nile red dying technique. PHA accumulation in the selected bacterium strain was confirmed by transmission electron microscope. With the exception of maltose or sucrose, the bacterium strain was found to be able to synthesize PHA from various carbon sources (glucose, xylose, fructose, glycerol, and glucose plus propionate). The strain accumulated poly(3-hydroxybutyrate) from glucose, fructose, xylose, and glycerol whereas poly(3-hydroxybutyrate-co-3-hydroxyvalarate) was produced when a combination of glucose and propionate was included in the culture medium. Fructose was found to be most suitable substrate for PHA synthesis by strain QN271. PHA content of 63.3% and CDW of 6 g/L were obtained after 32 hrs of cultivation in fructose medium. / Chủng vi khuẩn có khả năng sinh tổng hợp PHA đã được phân lập từ đất rừng ngập mặn tỉnh Quảng Ninh nhờ kỹ thuật nhuộm với Nile red. Ảnh quan sát dưới kính hiển vi điện tử dẫn truyền chứng tỏ rằng chủng vi khuẩn này có khả năng tích lũy lượng lớn PHA trong tế bào. Chủng vi khuẩn tuyển chọn có khả năng sinh tổng hợp PHA từ nhiều nguồn các bon khác nhau như glucose, xylose, fructose, glucerol, glucose và propionate nhưng không có khả năng tổng hợp PHA từ maltose hoặc saccharose. Chủng vi khuẩn tuyển chọn tổng hợp poly (3-hydroxybutyrate) từ các nguồn các-bon như glucose, xylose, fructose, hay glycerol, trong khi đó poly (3-hydroxybutyrateco- 3-hydroxyvalarate) sẽ được tổng hợp khi phối hợp sử dụng hai nguồn các-bon (glucose và propionate). Fructose là nguồn các-bon tốt nhất cho chủng QN271 sinh tổng hợp PHA, khi nuôi cấy trong môi trường có fructose chủng vi khuẩn này có thể tạo ra lượng sinh khối là 6 g/L trong đó có chứa 63.3% PHA sau 32 giờ.

No description available.

This thesis is inspired by a persistent limitation in the use of composite biomaterials for orthopaedic applications, namely the agglomeration of reinforcing particles in these composites, which has resulted in poor mechanical properties. The use of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and hydroxyapatite (HA) nanoparticles to produce biodegradable nanocomposites is investigated. More specifically, the thesis investigates different methods of composite processing, and interfacial modifying agents and the effect that these have on the nano- and micro- scale structure of composites and their mechanical properties. PHBV and HA were chosen because PHBV is a biodegradable/biocompatible polymer and it has a relatively high stiffness when compared to other biodegradable polymers frequently used in orthopaedic applications. HA is chemically similar to ceramic phase found in bones and hard tissues and the inclusion of HA into biomedical materials has been shown to enhance the rate of osteoconduction. HA/PHBV composites were produced using different dispersing agents including poly(acrylic acid) (PAA), a model dispersing agent, polyethyleneimine (PEI) which allowed for the development of a single solvent system for composite preparation, and heparin (Hep), a macromolecule which is produced in vivo. Additionally, HA/PAA/PHBV composites were prepared from both sonicated and non-sonicated HA/PAA suspensions up to approximately 17% by weight (wt %) of HA content. Attempts to prepare composites with higher HA loadings led to inhomogeneous composite mixtures, which were caused by the dual solvent system used for the composite preparation. The HA/PEI/PHBV and HA/Hep/PHBV composites were produced up to approximately 75 wt % of HA content. It was found that the HA/PEI/PHBV and HA/Hep/PHBV composites could be prepared at higher loadings than HA/PAA/PHBV composites due to the single solvent system used for the preparation of the HA/PEI/PHBV composites and the better dispersion of HA/Hep particles in precursor suspensions. Finally, selected HA/PEI/PHBV composites were further processed using a twin screw extruder. All of the composites were characterised in terms of their dispersion levels as well as their compressive mechanical properties. In addition, HA/PEI/PHBV composite reinforced with 20 wt % of HA content was also tested for its mechanical properties using three different test types; compression, three-point bending, and tensile tests. Finally, the HA/PAA/PHBV, HA/PEI/PHBV, and HA/Hep/PHBV composites were tested their compressive mechanical properties in wet state. It was found that the sonicated HA/PAA suspensions in general had better colloidal stability than non-sonicated ones and that this yielded composites with superior compressive moduli than those prepared from non-sonicated suspensions. In addition, the better dispersion of the particles in the composites prepared from the sonicated suspensions, as confirmed by transmission electron microscopic (TEM) images, led to higher percentage crystallinities when compared to the composites prepared from non-sonicated suspensions. It is likely that the greater number of individual HA particles and smaller HA agglomerates observed in the composites prepared from sonication treatment are acting as nuclei for crystal growth more effectively than large HA agglomerates. The largest modulus and yield strength that could be achieved with this system were approximately 1.45 GPa and 80 MPa, respectively. Composites of HA/PEI/PHBV and HA/Hep/PHBV with approximately 55 wt % of HA content were found to exhibit the largest compressive moduli of approximately 2.5 and 2.8 GPa, respectively. Moreover, the yield strengths for the same materials were found to be approximately 123 and 120 MPa, respectively. This was found to correlate with the better levels of dispersion within the nanocomposites that could be achieved using these stabilisers. The extruded samples were found to have an even greater degree of particle dispersion when compared to the unextruded ones. This improved degree of particle dispersion of the extruded samples resulted in higher moduli in comparison to unextruded samples. The largest compressive modulus and yield strength of the extruded samples were found to be approximately 3.2 GPa and 125 MPa, respectively. The compressive moduli of the composites produced in this thesis are significantly greater than that of cancellous bone (0.4 GPa), but significantly lower than that of cortical bone (12.8–17.7 GPa). However, maximum yield strengths of the HA/PEI/PHBV and HA/Hep/PHBV composites match to cortical bone (120–180 MPa), which is a noteworthy finding in this thesis. The wet mechanical results of all composites as well as pure PHBV polymer showed a reduction in both moduli and yield strengths when compared to dry state. In addition, after 2 weeks in wet state both moduli and yield strengths of the composites and pure polymer converged to approximately the same values. Finally, the HA/PEI/PHBV composite samples tested by tensile testing showed the highest Young’s modulus and those tested by compression testing possessed the lowest Young’s modulus. This resulted from the difference in periods of time for heating exposure and void contents of the tested samples, which were prepared by different methods. However, toughness values obtained from the samples tested using three-point bending and tensile tests, was not significantly different.

This thesis is inspired by a persistent limitation in the use of composite biomaterials for orthopaedic applications, namely the agglomeration of reinforcing particles in these composites, which has resulted in poor mechanical properties. The use of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and hydroxyapatite (HA) nanoparticles to produce biodegradable nanocomposites is investigated. More specifically, the thesis investigates different methods of composite processing, and interfacial modifying agents and the effect that these have on the nano- and micro- scale structure of composites and their mechanical properties. PHBV and HA were chosen because PHBV is a biodegradable/biocompatible polymer and it has a relatively high stiffness when compared to other biodegradable polymers frequently used in orthopaedic applications. HA is chemically similar to ceramic phase found in bones and hard tissues and the inclusion of HA into biomedical materials has been shown to enhance the rate of osteoconduction. HA/PHBV composites were produced using different dispersing agents including poly(acrylic acid) (PAA), a model dispersing agent, polyethyleneimine (PEI) which allowed for the development of a single solvent system for composite preparation, and heparin (Hep), a macromolecule which is produced in vivo. Additionally, HA/PAA/PHBV composites were prepared from both sonicated and non-sonicated HA/PAA suspensions up to approximately 17% by weight (wt %) of HA content. Attempts to prepare composites with higher HA loadings led to inhomogeneous composite mixtures, which were caused by the dual solvent system used for the composite preparation. The HA/PEI/PHBV and HA/Hep/PHBV composites were produced up to approximately 75 wt % of HA content. It was found that the HA/PEI/PHBV and HA/Hep/PHBV composites could be prepared at higher loadings than HA/PAA/PHBV composites due to the single solvent system used for the preparation of the HA/PEI/PHBV composites and the better dispersion of HA/Hep particles in precursor suspensions. Finally, selected HA/PEI/PHBV composites were further processed using a twin screw extruder. All of the composites were characterised in terms of their dispersion levels as well as their compressive mechanical properties. In addition, HA/PEI/PHBV composite reinforced with 20 wt % of HA content was also tested for its mechanical properties using three different test types; compression, three-point bending, and tensile tests. Finally, the HA/PAA/PHBV, HA/PEI/PHBV, and HA/Hep/PHBV composites were tested their compressive mechanical properties in wet state. It was found that the sonicated HA/PAA suspensions in general had better colloidal stability than non-sonicated ones and that this yielded composites with superior compressive moduli than those prepared from non-sonicated suspensions. In addition, the better dispersion of the particles in the composites prepared from the sonicated suspensions, as confirmed by transmission electron microscopic (TEM) images, led to higher percentage crystallinities when compared to the composites prepared from non-sonicated suspensions. It is likely that the greater number of individual HA particles and smaller HA agglomerates observed in the composites prepared from sonication treatment are acting as nuclei for crystal growth more effectively than large HA agglomerates. The largest modulus and yield strength that could be achieved with this system were approximately 1.45 GPa and 80 MPa, respectively. Composites of HA/PEI/PHBV and HA/Hep/PHBV with approximately 55 wt % of HA content were found to exhibit the largest compressive moduli of approximately 2.5 and 2.8 GPa, respectively. Moreover, the yield strengths for the same materials were found to be approximately 123 and 120 MPa, respectively. This was found to correlate with the better levels of dispersion within the nanocomposites that could be achieved using these stabilisers. The extruded samples were found to have an even greater degree of particle dispersion when compared to the unextruded ones. This improved degree of particle dispersion of the extruded samples resulted in higher moduli in comparison to unextruded samples. The largest compressive modulus and yield strength of the extruded samples were found to be approximately 3.2 GPa and 125 MPa, respectively. The compressive moduli of the composites produced in this thesis are significantly greater than that of cancellous bone (0.4 GPa), but significantly lower than that of cortical bone (12.8–17.7 GPa). However, maximum yield strengths of the HA/PEI/PHBV and HA/Hep/PHBV composites match to cortical bone (120–180 MPa), which is a noteworthy finding in this thesis. The wet mechanical results of all composites as well as pure PHBV polymer showed a reduction in both moduli and yield strengths when compared to dry state. In addition, after 2 weeks in wet state both moduli and yield strengths of the composites and pure polymer converged to approximately the same values. Finally, the HA/PEI/PHBV composite samples tested by tensile testing showed the highest Young’s modulus and those tested by compression testing possessed the lowest Young’s modulus. This resulted from the difference in periods of time for heating exposure and void contents of the tested samples, which were prepared by different methods. However, toughness values obtained from the samples tested using three-point bending and tensile tests, was not significantly different.

This thesis is inspired by a persistent limitation in the use of composite biomaterials for orthopaedic applications, namely the agglomeration of reinforcing particles in these composites, which has resulted in poor mechanical properties. The use of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and hydroxyapatite (HA) nanoparticles to produce biodegradable nanocomposites is investigated. More specifically, the thesis investigates different methods of composite processing, and interfacial modifying agents and the effect that these have on the nano- and micro- scale structure of composites and their mechanical properties. PHBV and HA were chosen because PHBV is a biodegradable/biocompatible polymer and it has a relatively high stiffness when compared to other biodegradable polymers frequently used in orthopaedic applications. HA is chemically similar to ceramic phase found in bones and hard tissues and the inclusion of HA into biomedical materials has been shown to enhance the rate of osteoconduction. HA/PHBV composites were produced using different dispersing agents including poly(acrylic acid) (PAA), a model dispersing agent, polyethyleneimine (PEI) which allowed for the development of a single solvent system for composite preparation, and heparin (Hep), a macromolecule which is produced in vivo. Additionally, HA/PAA/PHBV composites were prepared from both sonicated and non-sonicated HA/PAA suspensions up to approximately 17% by weight (wt %) of HA content. Attempts to prepare composites with higher HA loadings led to inhomogeneous composite mixtures, which were caused by the dual solvent system used for the composite preparation. The HA/PEI/PHBV and HA/Hep/PHBV composites were produced up to approximately 75 wt % of HA content. It was found that the HA/PEI/PHBV and HA/Hep/PHBV composites could be prepared at higher loadings than HA/PAA/PHBV composites due to the single solvent system used for the preparation of the HA/PEI/PHBV composites and the better dispersion of HA/Hep particles in precursor suspensions. Finally, selected HA/PEI/PHBV composites were further processed using a twin screw extruder. All of the composites were characterised in terms of their dispersion levels as well as their compressive mechanical properties. In addition, HA/PEI/PHBV composite reinforced with 20 wt % of HA content was also tested for its mechanical properties using three different test types; compression, three-point bending, and tensile tests. Finally, the HA/PAA/PHBV, HA/PEI/PHBV, and HA/Hep/PHBV composites were tested their compressive mechanical properties in wet state. It was found that the sonicated HA/PAA suspensions in general had better colloidal stability than non-sonicated ones and that this yielded composites with superior compressive moduli than those prepared from non-sonicated suspensions. In addition, the better dispersion of the particles in the composites prepared from the sonicated suspensions, as confirmed by transmission electron microscopic (TEM) images, led to higher percentage crystallinities when compared to the composites prepared from non-sonicated suspensions. It is likely that the greater number of individual HA particles and smaller HA agglomerates observed in the composites prepared from sonication treatment are acting as nuclei for crystal growth more effectively than large HA agglomerates. The largest modulus and yield strength that could be achieved with this system were approximately 1.45 GPa and 80 MPa, respectively. Composites of HA/PEI/PHBV and HA/Hep/PHBV with approximately 55 wt % of HA content were found to exhibit the largest compressive moduli of approximately 2.5 and 2.8 GPa, respectively. Moreover, the yield strengths for the same materials were found to be approximately 123 and 120 MPa, respectively. This was found to correlate with the better levels of dispersion within the nanocomposites that could be achieved using these stabilisers. The extruded samples were found to have an even greater degree of particle dispersion when compared to the unextruded ones. This improved degree of particle dispersion of the extruded samples resulted in higher moduli in comparison to unextruded samples. The largest compressive modulus and yield strength of the extruded samples were found to be approximately 3.2 GPa and 125 MPa, respectively. The compressive moduli of the composites produced in this thesis are significantly greater than that of cancellous bone (0.4 GPa), but significantly lower than that of cortical bone (12.8–17.7 GPa). However, maximum yield strengths of the HA/PEI/PHBV and HA/Hep/PHBV composites match to cortical bone (120–180 MPa), which is a noteworthy finding in this thesis. The wet mechanical results of all composites as well as pure PHBV polymer showed a reduction in both moduli and yield strengths when compared to dry state. In addition, after 2 weeks in wet state both moduli and yield strengths of the composites and pure polymer converged to approximately the same values. Finally, the HA/PEI/PHBV composite samples tested by tensile testing showed the highest Young’s modulus and those tested by compression testing possessed the lowest Young’s modulus. This resulted from the difference in periods of time for heating exposure and void contents of the tested samples, which were prepared by different methods. However, toughness values obtained from the samples tested using three-point bending and tensile tests, was not significantly different.

Disponibiliza??o em conte?do parcial do trabalho, conforme Termo de Autoriza??o. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2017-02-14T19:00:46Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-03-06T12:24:50Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) / Made available in DSpace on 2017-03-06T12:24:50Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lays_fernanda_nunes_dourado_parcial.pdf: 389665 bytes, checksum: 2289d8ac4ca389d5cdaf516878ddae78 (MD5) Previous issue date: 2016 / Na ind?stria farmac?utica, os pol?meros s?o capazes de desempenhar a fun??o de matriz para libera??o controlada de f?rmacos. Isto tem como vantagem a minimiza??o dos efeitos adversos dos medicamentos e a otimiza??o do tratamento. Entre os pol?meros utilizados para tal finalidade, tem-se o poli(3-hidroxibutirato) (PHB) conhecido por sua origem natural, um material que se degrada a produtos n?o t?xicos para o organismo, o que garante o seu emprego como biomaterial. Quando utilizado em associa??o a outros pol?meros, s?o denominados Blendas, essas misturas modificam as caracter?sticas f?sico-qu?micas dos pol?meros para serem empregados em finalidades diversas. Desta forma este trabalho teve como objetivo o desenvolvimento de uma matriz polim?rica capaz de ser utilizada para libera??o controlada de f?rmacos. Para tal, foram produzidas duas membranas diferentes uma de PHB e outra de Blenda Poli (3-hidroxibutirato)/Polipropilenoglicol, PHB/PPG (90:10), com concentra??es diferentes de f?rmaco, contendo 5% e 25% em massa. O f?rmaco modelo foi a Sinvastatina. Estes dispositivos foram produzidos por dissolu??o seguida de evapora??o do solvente, formando filmes de 0,5 mm de di?metro que foram analisados quanto a sua degrada??o in vitro e in vivo, em implantes subcut?neos. Os materiais foram analisados utilizando espectroscopia na regi?o do infravermelho, termogravimetria, microscopia eletr?nica de varredura e por testes histol?gicos. Os filmes ? base de PHB, apresentaram degrada??o in vitro e in vivo mais lenta quando comparados ?s blendas, no entanto em ambos os casos, os materiais que continham maior percentual de Sinvastatina apresentaram maior degrada??o e libera??o do f?rmaco. As l?minas histol?gicas revelam a presen?a do tecido em torno dos dispositivos e aus?ncia de inflama??o o que comprova a biocompatibilidade dos materiais estudados. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2016. / In the pharmaceutical industry, the polymers are able to drive the controlled release of drugs. Its brings the advantage of minimizing adverse effects of medicines and optimization of treatment. Among the polymers used for this purpose the poly (3-hydroxybutyrate) has known for their natural origin, its degradation to non-toxic effects to the life tissue which ensures their use as subcutaneous implants. A blend is a mixture of different polymers, these mixtures are able to modify the physicochemical characteristics of the polymers for several uses. This study aimed to develop a polymer matrix can be used as a way for controlled release of drugs. For this purpose, two different membranes were produced, the PHB and a Poly(3-hydroxybutyrate)/Polypropylene glycol blends, PHB/PPG (90:10), with different concentrations of drug with 5% and another 25%. The simvastatin was chosen as a model. These devices were manufactured by casting to form films of 0.5 mm diameter that were analyzed for in vitro and in vivo degradation tests using subcutaneous implants. The materials were analyzed using infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and histological tests. The films based on PHB presented a slower degradation in vitro and in vivo degradation tests when compared to the blends, however in both cases those materials containing a higher percentage of simvastatin has shown the higher degradation and release of the drug. The histological sections showed a tissue colonization and absence of inflammation which demonstrates the biocompatibility of the implants.

This master’s thesis deals with plasticization of poly(3-hydroxybutyrate), polylactid acid and their blend. It explores effect of chemical structure of plasticizer on mechanical properties of this polymer blend and on its diffusion from the polymer blend. Syntheses of plasticizers based on oligomeric polyadipates, citrates, lactate and esters of 2 ethylhexanoic acid with poly(ethyleneglycol) were carried out. Molecular weight distribution of synthesized plasticizers was determined using gel permeation chromatography. Poly(3-hydroxybutyrate), polylactid acid and their blend were plasticized with synthesized and commercial plasticizers. From commercial, chosed plasticizers were based on citrates and ester of 2-ethylhexanoic acid with poly(ethyleneglycol). Thermal stability of selected commercial plasticizers in polylactid acid was studied using thermogravimetry. Diffusion of plasticizers from poly(3-hydroxybutyrate), polylactid acid and their blend during exposure to 110 °C was also investigated. Mechanical properties of prepared blends were tested by tensile test. Almost all used plasticizers showed positive softening effect in blend. The highest elongation at break was detected for the blend with commercial acetyltributylcitrate, where elongation at break reached 328 % relative to 21 % for neat non-plasticized blend.