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This thesis reports three projects on mussel-inspired biomimetic materials based on dopamine crosslinkers. First, polyethylene glycol diacrylate (PEGDA) hydrogels with excellent cell attachment and tunable stiffness was fabricated based on this novel crosslinker. In vitro tests proved that the designed hydrogels had excellent cell adhesion, suggesting the developed hydrogels are promising for applications in tissue engineering. Second, dopamine crosslinker-conjugated gelatin-polycparolactone (PCL) nanofibrous sheet was developed. The sheet was then employed successfully to treat stomach incision without suture during surgery, showing promising to deal with treatments of fragile tissues and to avoid suture caused stress concentration. Third, a facile strategy to wrap cell into a tissue-engineered scaffold was developed, which is a self-rolling and conductive dopamine-based film. The RTPCR test indicated that cells have higher level of differentiation with higher concentration of MWCNTs. This suggests that the self-rolling conductive WCNT-dopamine-PEG hydrogel is a promising scaffolding material for bone regeneration. / October 2015

by Dai Kang Sheng. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 127-130.

Bioactive glasses undergo dynamic changes in vivo to produce an apatite layer permitting a strong bond with living tissues including both bone and soft tissues, and their compositions can be modified and tailored. The aim of this project was to generate high phosphate low fluoride containing bioactive glasses and explore their bioactivity and biological performances in vitro. Bioactive glasses (0-7% F- content, constant 6.33% P2O5 in Mol.%) were produced and the particles immersed in Tris Buffer solution or cell culture medium (α-MEM) to determine apatite formation and ion (Ca, P, Si and F) release. Bioactive glass conditioned medium was used to treat pre-osteoblasts MC3T3-E1 for cytotoxicity, pre-osteogenic and pro-angiogenic responses, and to human oral fibroblasts and epithelial cells for proliferation. Antibacterial ability was explored by incubating supra- and sub-gingival bacteria with bioactive glass particulates. Rapid apatite formation was observed in F- containing bioactive glasses after only 2 h immersion in Tris buffer solution, while it was not detectable until 72 h in the F- free bioactive glass. Alkaline phosphatase activity, cell number, collagen formation, bone-like mineral nodules and osteogenic gene expression of MC3T3-E1 cells were significantly promoted in low F- bioactive glass (P6.33F1) conditioned medium. MC3T3-E1 VEGF gene expression was increased, and protein production was dose-dependently promoted with F- containing bioactive glass conditioned medium, which also promoted human oral fibroblast proliferation, but suppressed epithelial cell numbers. After incubation with glass particulates, the growth of L. casei, S. mitis, A. actinomycetemcomitans and P. gingivalis, was significantly inhibited; the antibacterial activity being dependent on the F- content of the bioactive glasses. As a potential bone graft substitute in vivo, such novel bioactive glasses would be expected to stimulate bone formation and overcome problems associated with infection and the poor vascularisation in large bone graft sites. Additionally, they could reduce the need for further clinical intervention, and in particular, will be advantageous for the periodontal soft tissue regeneration.

Misregulation of Dlk1, a paternally expressed imprinted gene, is known to cause adipose phenotypes in both mice and humans. It is now known that the type of fat a person has, the location of and type of expansion are all important factors for the epidemic of obesity-related diseases, yet there is little understanding of the factors that influence which depots expand, and how. This project investigates how Dlk1, expressed primarily during embryogenesis, effects adulthood adiposity, which has shed light on the mechanism by which embryonic insults affect adulthood adipose physiology and resultant metabolic disease. Much previous work has been done on the role of Dlk1 in adipogenesis in vitro, however little is known of its role in this process in vivo. To achieve an in vivo investigation of its role in adipogenesis, adipose tissue has been measured in mice with deleted Dlk1 from embryo through early life and into adulthood. Gross measurement has been supported by mechanistic interrogation of adipose expandability using a triple transgenic adipocyte labelling mouse model, results from which are the most comprehensive to date in a wild type context and reveal insight into the Dlk1 knock-out phenotype. Results indicate a complex and dynamic role of Dlk1 that is interlinked with overall growth in mice. Moreover new evidence is presented here for tissue specific c imprinting of Dlk1 in some adipose cell types with consequential growth and adipose alterations in Dlk1 heterozygote mice that do not follow the expected phenotype of imprinted gene knock-out models.

Dental tissue conditioners are compliant, viscoelastic gels used primarily to form a soft cushion between the oral mucosa and the hard denture base. Their uses include the treatment of inflamed mucosa resulting from ill-fitting dentures and in treatment of denture related stomatitis. They are presented in powder/liquid format where the powder is usually poly(ethyl methacrylate) (PEMA) and the liquid is a mix of an aromatic ester (plasticiser, usually a phthalate) with ethanol. In use, the ethanol and plasticiser leach out with time causing the material to harden. In recent years there has been concern about possible toxic effects of the leached phthalate. Preliminary work has shown citrate plasticisers to be acceptable replacements for phthalates. Another disadvantage of the powder/liquid format is the porosity produced on mixing which can lead to microbial ingress and contamination. One possible solution would be to use a pre-gelled material which would have the advantages of easy application and reduced porosity. Candidal infections are a common etiological factor in denture related stomatitis. Earlier studies have shown it possible to release chlorhexidine diacetate (a broad spectrum antibacterial/antifungal agent) from powder/liquid tissue conditioners to treat these infections The aim of this study is to develop citrate-based pre-gelled and powder/liquid tissue conditioners and explore its use as potential drug delivery vehicle for chlorhexidine diacetate. The experimental pre-gelled system (EPGS) containing PEMA and acetyl tributyl citrate (ATBC) only showed stable Shore A hardness values over an 18 month time Abstract 5 period when stored at 7oC. The Shore A hardness and creep compliance ratio (flow) of EPGS indicated that it could be used as both a tissue conditioner and a temporary denture lining material, whereas experimental powder liquid system (EPLS), which contained 16 hours ball-milled PEMA powder and ATBC plus 5% ethanol, had more suitable properties for use as a tissue conditioner. Addition of chlorhexidine diacetate alone or with sodium fluoride did have an effect on the hardness and creep compliance ratio of the materials but these were within acceptable range. Both EPGS and EPLS containing 1% chlorhexidine had a higher percent release than those containing 9% chlorhexidine. The addition of sodium fluoride increased the release of chlorhexidine in all formulations.

Mon travail de thèse, débuté en septembre 2005, a été consacré au développement de l’émergente technique d’imagerie par spectrométrie de masse ToF-SIMS. Une première partie de ce travail a été orientée vers des aspects fondamentaux avec l’utilisation d’une source d’ions fullerènes comme faisceau d’ions primaires, mais aussi comme faisceau de pulvérisation. Le but était d’éprouver la possibilité de réaliser une imagerie 3D sur des échantillons biologiques par spectrométrie de masse ToF-SIMS. Une seconde partie de mon travail de thèse a été consacrée à l’utilisation de la technique proprement dite. Différents domaines d’application ont été étudiés, comme l’archéologie, avec l’analyse de la composition des patines recouvrant les statues rituelles de la tribu Dogon (Mali) ou l’étude de la dégradation de cheveux de momies chinoises. Un troisième projet a consisté à analyser in situ les surfactines, une famille de cyclodepsipeptides amphiphiles, sur des profils de colonisation de surface de Bacillus subtilis. Cette analyse qualitative par imagerie ToF-SIMS a été complétée par une analyse quantitative par spectrométrie de masse MALDI-TOF. Enfin, le dernier projet mis en œuvre durant ma thèse concerne la recherche de biomarqueurs lipidiques de la stéatose hépatique non alcoolique chez l’humain. Les résultats ont mis en évidence la complémentarité de l’imagerie par spectrométrie de masse avec d’autres techniques permettant la localisation de composés ciblés, comme la coloration histologique. Les résultats de cette thèse démontrent que l’imagerie par spectrométrie de masse ToF-SIMS peut être appliquée dans des domaines aussi divers que l’archéologie, la microbiologie ou la médecine. / My PhD’s work has been devoted to the development of the emergent technique ToF-SIMS imaging. The first part of my work was dedicated to fondamental aspects with the use of a fullerene ion source as a primary ion beam or sputtering ion beam. We expected to realize 3D imaging. The second part of my work consisted to applications of the mass spectrometry imaging. Several application fields were studied, as archeology as with the analysis of patina of the Dogon statuary or chinese mummy hair. A third project was dedicated to the in situ biomarker research from human liver biopsies. The goal of this study was to identify a potential lipid biomarker of the non-alcoholic fatty liver disease. The last part of this manuscript is devoted to the in situ qualitative and quantitative analysis of surfactins (a family of heptacyclodepsipeptides) on a Bacillus subtilis swarming community. We combined ToF-SIMS imaging for qualitative analysis and localization of surfactins within the swarming pattern and MALDI-TOF mass spectrometry for the quantification of these species. The results ot this PhD’s work show that ToF-SIMS imaging could be applied to various fields of research as archeology, microbiology and medicine.

Submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree Master of Science in Medicine (Bioethics and Health Law). Johannesburg, 2017 / Given the enormous gap between supply and demand for donor organs in South Africa, this research report seeks to answer the question ‘which system of organ donation is the most ethically and practically suitable for South Africa?’ I begin with an analysis of the varying aspects of the country that influence organ donation rates. Following this, opt-in, opt-out and mandated choice are all critically evaluated in terms of their suitability as organ procurement systems in the country. The four principles of autonomy, non-maleficence, beneficence and justice (theory of Principlism) are used to assess each system. In conclusion, a hybrid system of opt-in and mandated choice is argued to be the most ethically and practically appropriate system for South Africa to improve organ donation rates. As would be required for any improvement of the system, effort needs to be made to increase awareness on the topic of organ donation throughout South Africa. / MT2017

Thesis (Ph. D.)--Ohio State University, 2006. / Full text release at OhioLINK's ETD Center delayed at author's request

Tissue equivalent proportional counters (TEPCs) are commonly used for radiation monitoring in areas where a mixture of neutron and photon radiations may be present, such as those commonly encountered in nuclear power plants. In such radiation fields, the dose rate of each component can vary drastically from extremely low to very high. Among these possible combinations of radiation fields with very different dose rates, a mixed field of an intense photon and a weak neutron dose component is the more commonly encountered. This study describes the measurement of lineal energy spectra carried out with a 5.1 cm (2 inch) diameter spherical TEPC simulating a 2 μm diameter tissue site in low energy (33 – 330 keV neutrons) mixed photon-neutron fields with varying dose rates generated by the McMaster University 1.25 MV double stage Tandetron accelerator. The Tandetron accelerator facility was employed to produce neutrons using thick 7Li targets via the 7Li(p, n)7Be reaction. A continuous spectrum of neutrons is generated at any selected proton beam energy which is very narrow at beam energies very close to the threshold of the reaction 1.88 MeV and becomes wider as the proton beam energy moves further away from the threshold energy of the reaction. Dose rates which resulted in dead times as high as 75% for the data acquisition system were employed to study the effect of dose rate on the measured quality factors, microdosimetric averages (y ̅_f and y ̅_D)absorbed dose and dose equivalent. The dose rate at a given beam energy was varied by changing the accelerator beam current. A variety of mixed neutron gamma fields was generated using neutron beams with mean energies extending approximately from 33 keV to 330 keV with the 7Li target using proton beam energies ranging from 1.89 to 2.5 MeV. In direct beams, 478 keV photons which are produced in the 7Li target via inelastic scattering interaction 7Li(p, p'γ)7Li dominate the low LET component of the mixed field of radiation. When a 2 cm thick polyethylene moderator was inserted between the neutron producing target and the counter, the low LET component of the mixed radiation field also contained 2.20 MeV gamma rays originating from 1H(n, γ)2H capture interactions in the moderator. We have observed that high dose rates due to both photons and neutrons in a mixed field of radiation result in pile up of pulses and distort the lineal energy spectrum measured under these conditions. The pile up effect and hence the distortion in the lineal energy spectrum becomes prominent with dose rates which result in dead times larger than 25% for the high LET radiation component. In intense neutron fields, which may amount to 75% dead time, a 50% or even larger increase in values for the measured microsdosimetric averages and the neutron quality factor was observed. This study demonstrates that moderate dose rates which do not result in dead times of more than 20-25% due to either of the component radiations or due to both components of mixed field radiation generate results which are acceptable for operational health physics mixed neutron-gamma radiation monitoring using tissue equivalent proportional counters. / UOIT