published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

PURPOSE: The aim of this study is to examine the healing of intact extraction sockets grafted with leukocyte-platelet rich fibrin (L-PRF) as compared to sockets grafted with freeze-dried bone allograft (FDBA) and a resorbable collagen barrier membrane (RCM). METHODS: This prospective randomized, examiner blinded pilot study included 17 subjects randomized to two treatment groups. Serum total cholesterol, low density lipoprotein (LDL), 25-hydroxyvitamin-D3, and platelet counts were determined preoperatively in all subjects. The experimental arm consisted of 8 posterior tooth-bounded intact extraction sites receiving L-PRF plugs. The control group consisted of 9 posterior tooth-bounded intact extraction sites receiving FDBA and RCM. An acrylic stent was fabricated to take duplicate clinical and CBCT measurements immediately post-extraction and at time of implant placement. A repeat-measures analysis of variance was utilized for statistical analysis. RESULTS: The study failed to detect a clinical or radiographic difference between treatment groups in horizontal or vertical ridge dimension changes. Serum cholesterol, LDL, 25-hydroxyvitamin-D3, and buccal plate thickness had a non-significant effect on outcome measurements, although there was a high prevalence of hyperlidpidemia and hypovitaminosis in the study population. CONCLUSIONS: The alveolar ridge dimension changes in intact posterior extraction sockets may be similar when either L-PRF or FDBA and RCM are utilized as socket grafting material. Although there was a high prevalence of high cholesterol and low 25-hydroxyvitamin-D3 levels in the population, this study failed to detect a significant correlation between preoperative serum levels and postoperative ridge dimension changes.

L’objectif de cette étude consiste à synthétiser et caractériser de nouveaux matériaux hybrides organique/inorganique obtenus par greffage de poly(méthacrylate)s d’alkyle sur des nanoparticules de dioxyde de titane (TiO2) et d'oxyde de zinc (ZnO). Afin de mieux comprendre les facteurs influents les réactions mises en jeu lors d'un greffage à partir de la surface d'un oxyde métallique, nous avons choisi de travailler avec des nanoparticules disponibles commercialement et/ou élaborées. Des nanoparticules d’oxyde de zinc, de dimensions allant de 5 à 100 nm, ont été synthétisées par la méthode de précipitation, à température ambiante. La diffractométrie de rayons X (DRX) et la microscopique électronique à transmission (MET) ont permis de déterminer la structure cristalline, les dimensions et la morphologie des particules ainsi préparées. Les conditions de synthèse ont été optimisées afin d'augmenter la surface spécifique des particules tout en favorisant la présence de groupes hydroxyles en surface. La méthode de greffage de polymères méthacryliques a consisté à modifier préalablement la surface des nanoparticules par un agent de couplage réactif de type 3-méthacryloxypropyltriméthoxysilane (MPS). Les nanoparticules ainsi modifiées ont été caractérisées par spectroscopie (IRTF et RMN CP-MAS 13C et 29Si) et par analyse thermogravimétrique afin de confirmer la présence et la quantité de MPS greffé. Cet alcoxysilane, porteur d'une fonction méthacrylate, a permis de greffer des chaînes de poly(méthacrylate de méthyle), de poly(méthacrylate de tert-butyldiméthylsilyle) à partir de la surface des nanoparticules. La polymérisation radicalaire contrôlée par addition-fragmentation réversible (procédé RAFT) a été sélectionnée pour obtenir un contrôle des masses molaires, de faibles indices de polymolécularité et le greffage de copolymères diblocs. L'observation de ces nanoparticules hydrides en microscopie électronique à transmission montre clairement la présence d'une couronne de polymères à la surface des particules. L'étude de la stabilité thermique des nouvelles nanoparticules hybrides à base de ZnO a été réalisée par analyse thermogravimétrique sous atmosphère inerte. L'impact du procédé de polymérisation sur les mécanismes de dégradation thermique des polymères méthacryliques étudiés a été mis en évidence. Pour la première fois, des valeurs d'énergie d'activation ont été calculées sous atmosphère inerte et oxydante. / The objective of this study is to synthesize and characterize new organic/inorganic hybrid materials obtained by grafting methacrylic polymer through the surface of metal oxide nanoparticles. Commercially available titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles were used as raw materials. For a better understanding of parameters which influence the grafting efficiency of polymers, ZnO nanoparticles were synthesized using the precipitation method. The synthetic pathway was optimized to obtain nanoparticles with high surface area and surface hydroxylation. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used to determine the crystal structure, the size and morphology of nanoparticles. A polymerizable silane coupling agent, i.e. 3-(trimethoxysilyl)propylmethacrylate (MPS) was used to modify the surface of nanoparticules to obtain hydrophobic surface containing a polymerizable function. Fourier transform infrared (FTIR), solid-state (13C and 29Si) Nuclear Magnetic Resonance (NMR) spectroscopic investigations demonstrated that the silane coupling agent was fully hydrolyzed and linked to the hydroxyl groups already present on the particle surface through covalent and hydrogen bonds. Thermogravimetric data were helpful to quantify the amount of MPS linked to the nanoparticles surface. New poly(methacrylic ester)/ZnO and TiO2 nano-hybrid particles were prepared by in situ RAFT polymerization were prepared using the "grafting through" method. (Meth)acrylic homopolymers and diblock copolymers containing unconventional trialkylsilyl methacrylate (MASi) and methyl methacrylate (MMA) monomer units were grafted through the surface of nanosized particles modified by MPS. Results from FTIR and TGA analyses demonstrated that polymer chains were anchored on the nanoparticles surface. The thermal and thermo-oxidative degradation of methacrylic polymers and hybrid nanoparticles were also investigated by TGA. The effect of the RAFT polymerization on the thermal degradation of polymers was demonstrated. In addition, their apparent activation energy of degradation (Ea) was determined for the first time.

No description available.

Tooth extraction is necessary when there is advanced decay, significance trauma or injury to the oral cavity, misalignment associated with crowded teeth or even, poor eruption of third molars. Typically, during extraction procedures, bone grafting material is inserted to minimize bone loss. Bone grafting has become a standard procedure in dentistry and an essential component in modern medicine. The practice started nearly 350 years ago when a Dutch doctor in 1668 performed the first and successful bone grafting operation. Currently, research studies are ongoing to enhance the success and viability of dental reconstruction. This thesis examines the effect of varying dental graft techniques and methodology on the stability and long-term effect on the jawbone. These techniques include five primary bone grafting methods, onlay, inlay, ridge expansion, distracted osteogenesis and guided bone regeneration (GBR) have been approved to enhance the outcome of dental implants. The review has presented the documented limitations and viability of each method. In this paper, the alternatives to bone grafting have also been elaborated. Based on the findings depicted in this research, the following recommendations will assist in achieving the best jawbone outcomes in long-term and short-term assessments. These recommendations are as follows, a proper evaluation of each patient to determine their health condition. The nature of the infection, injury, and trauma that led to the extraction of the tooth should be well documented. The selection of technique pertaining to dental restoration, functionality, and aesthetic needs are of primary factors considered. A proper clinical follow-up and monitoring of recovery process is an essential part that contributes to valid results. Finally, patient awareness is essential as well. The study found out that although some of the bone grafting techniques have shown a high survival rate, significant alveolar bone quality and quantity, and success of the implants, several reports that the use of bone grafts and implants is a practice that will still dominate dental surgery and attract more clinical assessments.

A cirurgia de reconstrução de mama é uma ferramenta cirúrgica de importância ímpar para reparar os defeitos e assimetrias causadas pelos vários tipos de tratamentos cirúrgicos do Câncer de mama. Várias técnicas e táticas têm sido demosntradas e aplicadas nos últimos anos. Muitos são os estágios em que se encontram os pacientes e vários são os esquemas de abordagem terapêutica para diferentes estágios e tipos histológicos que se apresentam. Tratamentos quimioterápicos pré ou pós-operatório, tratamento radioterápico no pós-operatório quase imediato, mastectomias preventivas, setores amplos em diferentes quadrantes, quadrantectomias, todos estes são vários aspectos de tratamento de uma mesma patologia, porém com estágios e características histológicas e moleculares diferenciadas. Como alternativa cirúrgica para reconstrução de mama em câncer de mama, nos casos em que está indicada a quadrantectomia e/ou setor de mama, independentemente da localização na mama, é que propusemos uma técnica de uso de enxerto autólogo da mama contralateral para manter a forma e a simetria mamária associada a técnicas cirúrgicas de mamoplastias. Objetivo: O objetivo do presente estudo foi avaliar o uso de enxerto de mama contralateral associada a outras técnicas de cirurgia mamária já descritas por outros autores e acompanhar o resultado quanto à estética e simetria mamária no pós-operatório imediato e após o tratamento radioterápico. Comparar os resultados com as mamas do pré-operatório e avaliar a simetria e a estética no pós-operatório. Métodos: Foram incluídos neste estudo 42 pacientes com diferentes tratamentos, porém todas com indicação cirúrgica semelhantes: setor de mama ou quadrantectomia, seguidos de radioterapia. Todos os casos foram fotografados no pré-operatório e mais de 3 meses pós-tratamento radioterápico. Foi utilizada uma escala contínua para avaliar o grau de simetria mamária no pós-operatório de mais de 3 meses de radioterapia. A escalala de medição se baseou numa régua milimétrica de 0 a 10 cm. Foi solicitado a quatro especialistas na área para colocar uma marca na escala com relação à simetria e ao aspecto estético das mamas. As notas de cada paciente foram avaliadas estatisticamente. Resultados: Os resultados foram estatisticamente significativos para a avaliação estética e para a simetria mamária pós-cirurgia e radioterapia. Conclusão: Cocluímos que o enxerto autólogo de mama contralateral em cirurgia de reconstrução de mama é um procedimento que, quando utilizado com outras técnicas, traz um resultado estético e simétrico adequado, desta forma mostrando mais uma alternativa para cirurgia de reconstrução mamária. / Background: The Breast Reconstruction surgery is a surgical tool of unparalleled importance to repair the defects and asymmetries caused by various types of surgical breast cancer treatment. Various techniques and tactics has been demonstrated and applied in recent years. Many patients are at different stages of the disease and several are the sorts of therapeutic approaches for different stages and histologic types that feature. Neo adjuvant chemotherapy treatments or postoperative chemotherapy, radiotherapy in almost immediately after surgery, preventive mastectomies, removing large breast tissue in different quadrants, quadrantectomies. All these are various aspects of treatment of the same disease however to different stages and histological and molecular characteristics. As a surgical alternative to breast reconstruction in breast cancer, where it is indicated quadrantectomy and or wide resection of breast tissue in the same quadrant, regardless of location in the breast that I proposed a technique contralateral breast grafiting replacement to keep shape and breast symmetry. Objetive: The aim of this study was to evaluate the contralateral breast graft associated with other breast surgery techniques already described by other authors, and follow the aesthetic result in the immediate postoperative period and after three months of radiotherapy. Compare the results with those of preoperative breast, and evaluate the symmetry postoperatively and proper aesthetic result. Methods: The study included 42 patients. Each case with different proposals for treatment, but all with similar surgical indication, wide resection of the breast or quadrantectomy, followed by radiotherapy. All cases were photographed in their preoperative, “pre radiotherapy” and three months post radiotherapy. A continuous scale was used to assess the degree of mammary symmetry in these patients in the post operative period of three months after radiotherapy. The measurement was based on a rule millimeter scale from 0 to 10 cm. We were asked to four experts in the field to put a mark on the scale with respect to symmetry and aesthetic appearance of the breasts. The scores of each patient were evaluated statistically. Results: The results were statistically significant for the aesthetic evaluation of the breasts and also for evaluation of the symmetry of the breasts after surgery and radiotherapy. Conclusion: We concluded that autologous graft contralateral breast in breast reconstruction surgery is a procedure that when used with other techniques, brings an aesthetic and suitable symmetrical result thus showing an alternative to breast reconstruction surgery.

Bone is the most commonly replaced organ, with nearly 1 million grafting procedures performed annually in the United States. Inherent limitations associated with bone grafts, such as graft availability and donor site morbidity, leave room for alternative grafting solutions. Current mineralized tissue engineering approaches include the use of synthetic hydroxyapatite as cement or as nano- or micro-particles pre-incorporated into a tissue engineering scaffold prior to cell seeding or implantation. While promising results have been reported with such methods, these constructs are not biomimetic as they fail to replicate neither the size, distribution, nor density of mineral inherent in the native bone, leading to inferior mechanical properties and supra-physiologic levels of calcium phosphate that can disrupt healing, alter cell response and inhibit normal tissue homeostasis. To address these issues, inspiration is taken from the native biomineralization process which is often facilitated by matrix vesicles, a lipid-based nanocarrier within which calcium and phosphate ions are combined to form calcium phosphate mineral in hard tissues such as bone. Synthetic matrix vesicles (SMV) formulated from self-assembling liposomes have emerged as a promising model both for studying the biomineralization process as it relates to matrix vesicles and for use in regenerative medicine. The ideal SMV system is defined as follows: the mineral formed should match the native calcium phosphate in both structure and chemistry, the mineral must be stable in the physiological environment and can continue to grow in size when necessary and the matrix vesicles should also be able to work in conjunction with a scaffold tailored for bone tissue engineering. It is hypothesized that the formation of native bone-like calcium phosphate can be achieved with the controlled optimization of matrix vesicles in terms of fabrication parameters, ion transport, cell response and interactions with a gelatinous matrix. To this end, a liposome-based, biomimetic matrix vesicle system was designed to facilitate vesicle-mediated biomineralization for regeneration of calcified tissues. Synthetic matrix vesicles were fabricated from two different phospholipids, DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and DMPC (1,2-bis(myristoyl)-sn-glycero-3-phosphocholine) and optimized in terms of membrane composition, alkaline phosphatase bioconjugation, and ion encapsulation. Calcium (Ca2+) and phosphate (Pi) ions were successfully encapsulated within the liposomes. Ion permeability across the bi-layer membrane, which is necessary for Ca2+ and Pi to combine within the SMV for mineralization, was found to increase with increasing DMPC composition, validated through ion release studies and diffusion modeling through Fick's 2nd Law. In addition, alkaline phosphatase (ALP), an enzyme which cleaves Pi from organic phosphate molecules for mineral formation with Ca2+, was successfully conjugated to the SMV membrane through the use of biotin-functionalized phospholipids and streptavidin-ALP. Human osteoblast-like cells were dosed with the optimized SMV and the effects of SMV type and dosage on mineralization response was evaluated. Mineralization potential of human osteoblast-like cells was found to decrease through exposure to Pi-encapsulated SMV similar to the response found for human osteoblast-like cells supplemented with beta-glycerophosphate (beta-GP), an organic phosphate source typically used in mineralization in vitro studies. Human osteoblast-like cells were also dosed with two different configurations of ALP SMV liposomes with ALP bound within (ALP-inside SMV) and liposomes with ALP bound to the membrane on the outside (ALP-outside SMV). ALP-outside SMV were ultimately selected for further study since the location of the ALP in the outside configuration more closely mimics the structure of native matrix vesicles. While mineral-like structures were observed in several types of SMV under cryo-electron microscopy, no bulk mineralization was observed by human osteoblast-like cells from SMV supplementation alone. This motivated a dosage study conducted with the Pi SMV which optimized the cell-to-liposome ratio and the concentration of Pi encapsulated. The optimized ALP-outside SMV and Pi SMV were individually combined with an electrospun gelatin nanofiber scaffold to further promote cell mineral deposition by acting as a biomimetic substrate for calcium phosphate nucleation. It was demonstrated that in the absence of growth factor stiumulation, culture of human osteoblast-like cells with SMV+beta-GP and Pi SMV resulted in mineral deposition on the gelatin nanofiber scaffold. Human mesenchymal stem cells (hMSC), a more clinically relevant cell type, were also cultured on the SMV-gelatin scaffold system. Mineralization potential was found to increase for hMSC cultured with ALP SMV, and the osteogenic marker osteocalcin was upregulated for cultures with Pi SMV. Dosage of hMSC with SMV+beta-GP and Pi SMV alone resulted in the formation of a mineralized matrix. In summary, this thesis focuses on the design of a biomimetic, liposome-based synthetic matrix vesicle system and elucidates the compositional and dosage parameters for the formation of calcified tissue by human osteoblast-like cells and MSCs. The synthetic matrix vesicle system developed in this thesis can be utilized for further investigation into the mechanisms of biomineralization, in addition to its potential for use in promoting cell-mediated regeneration of a variety of calcified tissues, including bone, teeth and mineralized soft-to-hard tissue interfaces.

Este trabalho tem como escopo o desenvolvimento de um modelo matemático representativo do processo de enxerto de anidrido maleico em polietileno, processo conhecido como grafting, com o objetivo de prever as modificações no grau de enxerto e teor de gel. Neste processo utiliza-se um iniciador, geralmente um peróxido, para gerar radicais livres, os quais abstraem hidrogênio das moléculas do polímero, gerando radicais poliméricos. O anidrido maleico pode reagir com estes radicais poliméricos, enxertando-se à cadeia polimérica, ou com os radicais fragmentos do iniciador. O mecanismo inclui também as reações de terminação entre os diferentes tipos de radicais presentes. O teor de gel é calculado a partir do grau de formação de ligações cruzadas utilizando-se a aproximação de Charlesby-Pinner. As constantes cinéticas do modelo foram estimadas via regressão não-linear, usando dados experimentais obtidos na literatura, e o modelo foi validado com outros conjuntos de dados, também obtidos da literatura. O modelo obtido mostrou-se capaz de representar adequadamente os dados experimentais em diferentes condições. / The scope of this work is the development of a mathematical model that can represent the process of grafting of maleic anhydride in polyethylene. The objective of this model is to preview the main modifications in polymer structure, as degree of grafting and degree of gel. In this process, an initiator, generally a peroxide) is used to generate free radicals that can abstract hydrogen from the polymer molecules, producing polymeric radicals. Maleic anhydride can react with these polymeric radicals, resulting in grafted polymer chains, or with the initiator radicals. This mechanism includes termination reactions between the different types of radicals present. Gel content was calculated from the crosslinking degree using the approximation of Charlesby-Pinner. Kinetic constants of the model were estimated through non-linear regression, by fitting the model to experimental data taken from literature. The model obtained was further tested using other data sets obtained from literature. The developed model was able to represent adequately the experimental data under different conditions.