No description available.

Ce travail de thèse traite du développement d’une maille en titane imprimée en 3D pour le comblement des grands défauts osseux. La perte de substance osseuse intervient lors de traumatismes importants ou de chirurgies ablatives (dues à des infections ou à des cancers). Lorsque le défaut atteint un stade critique, la régénération osseuse est impossible et on assiste à une perte de fonction. Il faut alors recourir à des chirurgies reconstructrices comme par exemple la reconstruction mandibulaire. Aujourd’hui, la chirurgie communément pratiquée pour reconstruire la mandibule est la reconstruction par lambeaux libres de fibula, laquelle demande un investissement en temps et en ressource colossale pour des résultats mitigés avoisinant les 10% de taux d’échec. En nous basant sur la littérature internationale, nous avons développé une maille en titane imprimée en 3D pour remplacer l’autogreffe de fibula et ainsi limiter les effets secondaires liés au site donneur tout en offrant aux cellules mésenchymateuses des conditions optimales à la colonisation osseuse. D’un point de vue mécanique, cela consiste à abaisser la rigidité native du titane (110GPa) à une rigidité comprise entre 0,1 et 1 GPa. Pour réaliser cette maille, nous avons mis en place une méthodologie de design qui nous a permis d’innover en mettant au point un système de reprise de charge. Ce système de reprise de charge permet d’adapter la réponse de l’implant en fonction de l’intensité de la sollicitation, ce qui permet de combiner une rigidité faible et une résistance à l’effort élevée. Les différentes itérations de design ont été testées par éléments finis, jusqu’au motif final, lequel a été caractérisée lors de tests mécaniques réels en compression, en traction et en flexion. Remplissant la majorité du cahier des charges, nous avons ensuite mis au point une étude animale, laquelle sera réalisée ultérieurement. Enfin, cette étude a permis de mettre en évidence certaines limitations de l’impression 3D métallique, principalement liés aux surfaces non supportées que nécessitent la reprise de charge. Cette maille très prometteuse est aujourd’hui en cours d’optimisation pour permettre d’être rapidement mise à la disposition des patients. / The work detailed in this thesis is about a titanium 3D printed mesh for large bone defects. Large bone defects are often due to surgical resections, performed after a cancer or an infection. When the defect reach a critical size, bone regeneration is impossible and it often leads to the loss of function. When it happened, the wound need to be cured using reconstructive surgery. The mandibular reconstruction is one of the most performed reconstructive surgery. Nowadays, we reconstruct the mandible with the fibula free flap technique, which require huge amount of time and resources for mixed results (around 10% failure rate). Based on the international literature, we developed a titanium 3D printed mesh to replace the fibula autograft and limit its side effect while offering to mesenchymal cells optimal growing environment. On the mechanical point of view, this environment requires to decrease the titanium initial rigidity from 110GPa to a range between 0.1 and 1GPa. In order to achieve that goal, we have developed a design methodology that lead us to innovation. We developed a load restauration system that allow us to combine low rigidity and high resistance. In order to find the final design, we used finite element modeling. Then, the final design have been tested mechanically in compression, traction and flexion. Because most of the requirements were reached, we designed an animal study which should take place in the next years. Eventually, we discovered some limitation for metallic 3D printing, essentially due to unsupported areas required for the load restauration. This innovative mesh is today optimized in order to be rapidly given to patients in the need.

O presente trabalho avaliou a formacao de tecido osseo ao redor de implantes osseointegraveis de titanio, apos realizacao de defeitos osseos, utilizando diferentes tipos de substitutos osseos. Foram utilizados 5 caes de raca indeterminada, os pre molares e molares mandibulares foram extraidos, passados 12 semanas, os caes foram submetidos a um novo procedimento cirurgico aonde foram realizadas as perfurações preconizados pelo fabricante dos implantes, o osso vestibular da mandibula foi desgastado ate que parte da perfuracao fosse exposta, os implantes entao foram colocados nas respectivas perfuracoes, ficando com 4 espiras expostas. Esses defeitos foram preenchidos aleatoriamente com Bioglass® 45S5, Biosilicato® , Osso autogeno, e sem nenhum material de preenchimento. 18 semanas depois da colocacao dos implantes os caes foram mortos e suas hemi-mandibulas contendo os implantes removidas e submetidas aos analises histologiaos e histomorfometricas, os dados obtidos foram submetidos ao teste de Kruskal-Wallis. A histologia dos 4 grupos estudados revelaram a presenca de tecido osseo maduro em contato com os implantes, porem sem ralacao direta com os vidros bioativos e osso autogeno. A porcentagem de contato osso implante, matriz ossea mineralizada ao redor da espira, e area de espelho, nao mostraram diferencas estatisticas significantes entre os 4 materiais testados. Os resultados indicam que a presenca de substitutos osseos nao interfere com a formacao ossea ao redor dos implantes nesse modelo experimental. E existe resposta tecidual muito semelhante entre o osso autogeno, Bioglass® 45S5 e Biosilicato. / The aim of the present study was to investigate the amount of bone formation on Ti implants in sites with intra-bony defects filled with different bone substitutes. Mandibular premolars and first molars were extracted from 5 dogs, and after 12 weeks 3 implants were bilaterally placed in sites with intra-bony defects and each implantation site randomly received the following treatment: Biosilicate®, Bioglass® 45S5, aoutologous bone or no treatment. At 18 weeks after implantation, the hemi-mandibles containing the implants were removed and processed for morphological and histomorphometric analysis. Data were submitted to Kruskal-Wallis and Fishers test. The histological sections of the 4 experimental groups exhibited mature bone tissue in contact with implants, but not related with bioactive glasses or autologous bone used. The percentage of bone-implant contact, mineralized bone matrix between implant threads, and mineralized bone matrix within mirror area in the treated or non-treated sites were not statistically different among the 4 experimental groups. These results indicates that the presence of the bone substitutes evaluated here did not interfere with bone formation on Ti implants in sites with intra-bony defects. In addition, tissue response to Biosilicate® was similar to that of Bioglass® 45S5 and autologous bone.

Made available in DSpace on 2016-04-28T20:18:26Z (GMT). No. of bitstreams: 1 Daniel de Almeida Balthazar.pdf: 1401083 bytes, checksum: 83ae40c829fabdead6d9cbc1eed23316 (MD5) Previous issue date: 2010-06-22 / Fractures in birds represent a challenge for surgeons because bone peculiar characteristics associated with the type of trauma which these species are exposed, in many cases determine the type comminuted fractures or even loss of bone segments.The aim of this study was to evaluate the effect of cortico-cancellous bone grafting in osteogenesis in cortical ulnar failure of domestic chickens (Gallus domesticus) by the clinical, radiological and histopathological study of bone healing. Eighteen female chickens, weighting two and half kilograms with approximately 70 weeks were used. In order to reduce the numbers of animals the both wings were used. For the purpose of reducing the number of animals used, they were subjected to surgical process on both wings, each included in the Control group (Group I) or treated (Group II), and randomly divided into four sub-groups according to the observation period. After fasting from food and water six hours was applied pre-anesthesia and subsequently performed with mask induction followed by intubation and maintenance circuit rebreathing. After reaching the proper anesthetic plane, the side of right ulna was surgically accessed, where it was created a failure of cortical approximately 3.3 mm in width and 1.6 mm in depth. The same procedure was performed in the left wing and after surgical access to the keel of the sternum were removed two bone fragments, which were immediately cut into pieces of approximately 3mm and implanted in bone defects already created in the left ulna. Clinical evaluation was done daily until the 10th postoperative day, then going to weekly until the end of the observation period of each group (14, 35, 60 and 90 days) when the animals were killed with sodium pentobarbital and fragments were collected from right and left ulnae achievement of histopathological and radiographic postmortem injuries. The only abnormality observed was hematoma, with resolution to 5 days. Comparing groups I and II at different times, it was observed that there was a statistically significant difference (p <0.05) in the radiological and histological parameters of proliferation between control and treated groups at 35 and 90 days after surgery. However, at times 14 and 60 days there were no significant differences. Compared to the 18 animals of the treated and control groups without taking into account the time of observation, a statistically significant difference was noted (p <0.05) between the two groups. Based on these results, we can conclude that the evolutionary process of incorporation of cortico-cancellous bone graft was found to be quite similar to that reported in small animals, and has demonstrated a satisfactory osteogenic potential, even revealing the need for a time to suffer greater bone remodeling when placed on bone defects stable form small gaps. / As fraturas em aves representam um desafio para os cirurgi?es, pois suas caracter?sticas ?sseas peculiares associadas ao tipo de trauma a que geralmente essas esp?cies s?o expostas determinam fraturas cominutivas ou at? mesmo a perda de segmentos ?sseos. O objetivo do presente estudo foi avaliar o efeito do enxerto ?sseo c?rtico-esponjoso na osteog?nese em falha cortical ulnar de galinhas dom?sticas (Gallus domesticus), atrav?s do acompanhamento cl?nico, radiol?gico e histopatol?gico da repara??o ?ssea. Foram utilizadas 18 galinhas, f?meas, com idade aproximada de 70 semanas, pesando aproximadamente dois quilos e meio. Para efeitos de redu??o no n?mero de animais utilizados, os mesmos foram submetidos ao processo cir?rgico em ambas as asas, cada uma inclu?da no grupo Controle (Grupo I) ou tratado (Grupo II), e subdivididos aleatoriamente em quatro sub-grupos de acordo com o per?odo de observa??o. Ap?s jejum h?drico e alimentar de 6 horas foi aplicada pr?-anestesia e posteriormente realizada indu??o anest?sica com m?scara, seguindo-se a intuba??o e manuten??o em circuito sem reinala??o. Ap?s atingirem o plano anest?sico adequado, a face lateral da ulna direita foi acessada cirurgicamente, local onde criou-se uma falha cortical de aproximadamente 3,3 mm de largura e 1,6 mm de profundidade. O mesmo procedimento foi realizado na asa esquerda e, ap?s acesso cir?rgico ? carena do esterno, foram retirados dois fragmentos ?sseos, os quais foram imediatamente seccionados em peda?os com aproximadamente 3mm e implantados na falha ?ssea j? criada na ulna esquerda. Avalia??o cl?nica foi di?ria at? o 10? dia p?soperat?rio, passando ent?o a semanal at? o final do per?odo de observa??o de cada grupo (14, 35, 60 e 90 dias), quando os animais foram abatidos com tiopental s?dico e foram coletados fragmentos das ulnas direita e esquerda para realiza??o dos exames histopatol?gico e radiogr?fico post-mortem das les?es. A ?nica altera??o cl?nica observada foi hematoma com resolu??o ao 5? dia. Comparando-se os grupos I e II nos diferentes tempos, foi poss?vel observar que houve diferen?a estat?stica significante (p<0,05) nos par?metros radiol?gicos e histopatol?gicos de prolifera??o entre os grupos controle e tratado aos 35 e 90 dias de p?scir?rgico. Entretanto, nos momentos 14 e 60 dias n?o foram observadas diferen?as estat?sticas significantes. Quando foram comparados os 18 animais dos grupos Controle e Tratado sem levar-se em conta o tempo de observa??o, foi notada diferen?a estat?stica significante (p<0,05) entre os dois grupos. Com base nos resultados obtidos, pode-se concluir que o processo evolutivo de incorpora??o do enxerto ?sseo c?rtico-esponjoso mostrou-se bastante semelhante ao relatado em pequenos animais, al?m de ter demonstrado um potencial osteog?nico satisfat?rio, mesmo sendo observada a necessidade de um tempo maior para sofrer remodela??o ?ssea quando colocado sobre falhas ?sseas est?veis que formam pequenas lacunas.

The management of significant bone defects, delayed and non-union of fractures can be extremely challenging. Development of specific treatment is hindered by an absence of information regarding the molecular events which regulate these processes. In this thesis, a bilateral cancellous bone defect model of the femur and tibia was developed in a rodent and the spatiotemporal profile of TGF-β, BMP 2 and 7, Smads 1, 4 and 5 characterised. Next, the capability of acid solution to augment healing was tested in both a bone defect and in a closed femoral fracture model. Finally, a long term oestrogen deficiency (OVX) rat model of postmenopausal osteoporosis was characterised and the spatiotemporal profiles of IGF-1, IGFR-1, MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, BMP-2, BMP-4, BMP-7, TGF-β, Smad4, Smad7, VEGF, Flt-1, Ihh and FGF-2 were compared in femoral osteotomies between OVX and Sham groups. The bilateral cancellous defect model was successfully created with a number of advantages with which to recommend its use in future studies. TGF-β, BMP 2 and 7, Smads 1, 4 and 5 had characteristic spatiotemporal profiles during cancellous bone defect healing suggesting that they have a regulatory role. The results of the acid study were inconclusive and problems with substance delivery and maintenance at the desired site need to be addressed in the future to fully test this hypothesis. No significant differences were detected on histology or three-point mechanical testing between the fracture calluses of acid and control groups. In the final study, OVX rats after six months had significantly increased weight and decreased bone mineral density compared to their sham counterparts. A histological delay in osteotomy healing was observed in the OVX group but no significant differences on tensile testing were seen between OVX and Sham groups up to six weeks. Immunohistochemistry revealed that delayed healing may be due to the down-regulation of IGF-1, BMP-2, 4, and 7 and the up-regulation of MMP-3 in OVX compared to Sham groups. In conclusion, the results of this thesis give some insight into the molecular biology of bone defects and osteoporotic fractures. This information may also be useful in the development of specific treatments aimed at augmenting healing in bone defects and osteoporotic fractures.

The management of significant bone defects, delayed and non-union of fractures can be extremely challenging. Development of specific treatment is hindered by an absence of information regarding the molecular events which regulate these processes. In this thesis, a bilateral cancellous bone defect model of the femur and tibia was developed in a rodent and the spatiotemporal profile of TGF-β, BMP 2 and 7, Smads 1, 4 and 5 characterised. Next, the capability of acid solution to augment healing was tested in both a bone defect and in a closed femoral fracture model. Finally, a long term oestrogen deficiency (OVX) rat model of postmenopausal osteoporosis was characterised and the spatiotemporal profiles of IGF-1, IGFR-1, MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, BMP-2, BMP-4, BMP-7, TGF-β, Smad4, Smad7, VEGF, Flt-1, Ihh and FGF-2 were compared in femoral osteotomies between OVX and Sham groups. The bilateral cancellous defect model was successfully created with a number of advantages with which to recommend its use in future studies. TGF-β, BMP 2 and 7, Smads 1, 4 and 5 had characteristic spatiotemporal profiles during cancellous bone defect healing suggesting that they have a regulatory role. The results of the acid study were inconclusive and problems with substance delivery and maintenance at the desired site need to be addressed in the future to fully test this hypothesis. No significant differences were detected on histology or three-point mechanical testing between the fracture calluses of acid and control groups. In the final study, OVX rats after six months had significantly increased weight and decreased bone mineral density compared to their sham counterparts. A histological delay in osteotomy healing was observed in the OVX group but no significant differences on tensile testing were seen between OVX and Sham groups up to six weeks. Immunohistochemistry revealed that delayed healing may be due to the down-regulation of IGF-1, BMP-2, 4, and 7 and the up-regulation of MMP-3 in OVX compared to Sham groups. In conclusion, the results of this thesis give some insight into the molecular biology of bone defects and osteoporotic fractures. This information may also be useful in the development of specific treatments aimed at augmenting healing in bone defects and osteoporotic fractures.

O presente trabalho avaliou a formacao de tecido osseo ao redor de implantes osseointegraveis de titanio, apos realizacao de defeitos osseos, utilizando diferentes tipos de substitutos osseos. Foram utilizados 5 caes de raca indeterminada, os pre molares e molares mandibulares foram extraidos, passados 12 semanas, os caes foram submetidos a um novo procedimento cirurgico aonde foram realizadas as perfurações preconizados pelo fabricante dos implantes, o osso vestibular da mandibula foi desgastado ate que parte da perfuracao fosse exposta, os implantes entao foram colocados nas respectivas perfuracoes, ficando com 4 espiras expostas. Esses defeitos foram preenchidos aleatoriamente com Bioglass® 45S5, Biosilicato® , Osso autogeno, e sem nenhum material de preenchimento. 18 semanas depois da colocacao dos implantes os caes foram mortos e suas hemi-mandibulas contendo os implantes removidas e submetidas aos analises histologiaos e histomorfometricas, os dados obtidos foram submetidos ao teste de Kruskal-Wallis. A histologia dos 4 grupos estudados revelaram a presenca de tecido osseo maduro em contato com os implantes, porem sem ralacao direta com os vidros bioativos e osso autogeno. A porcentagem de contato osso implante, matriz ossea mineralizada ao redor da espira, e area de espelho, nao mostraram diferencas estatisticas significantes entre os 4 materiais testados. Os resultados indicam que a presenca de substitutos osseos nao interfere com a formacao ossea ao redor dos implantes nesse modelo experimental. E existe resposta tecidual muito semelhante entre o osso autogeno, Bioglass® 45S5 e Biosilicato. / The aim of the present study was to investigate the amount of bone formation on Ti implants in sites with intra-bony defects filled with different bone substitutes. Mandibular premolars and first molars were extracted from 5 dogs, and after 12 weeks 3 implants were bilaterally placed in sites with intra-bony defects and each implantation site randomly received the following treatment: Biosilicate®, Bioglass® 45S5, aoutologous bone or no treatment. At 18 weeks after implantation, the hemi-mandibles containing the implants were removed and processed for morphological and histomorphometric analysis. Data were submitted to Kruskal-Wallis and Fishers test. The histological sections of the 4 experimental groups exhibited mature bone tissue in contact with implants, but not related with bioactive glasses or autologous bone used. The percentage of bone-implant contact, mineralized bone matrix between implant threads, and mineralized bone matrix within mirror area in the treated or non-treated sites were not statistically different among the 4 experimental groups. These results indicates that the presence of the bone substitutes evaluated here did not interfere with bone formation on Ti implants in sites with intra-bony defects. In addition, tissue response to Biosilicate® was similar to that of Bioglass® 45S5 and autologous bone.

Bioactive agents are proteins that regulate cellular activities including cell migration, proliferation, differentiation and matrix synthesis. Over the last decades there has been a focused effort to understand how these agents influence repair or regeneration of bony defects. Platelet derived growth factor (PDGF) has potent chemotactic and angiogenic properties. Bone morphogenetic protein (BMP) is a known factor for osteoblasts. This study evaluated the impact of recombinant human PDGF and BMP-2 on resolution of critical bony defects (2 mm) using mouse calvarial bone cultures. Calvaria from 5-7 day neonatal CD-1 mice were dissected and cultured in Dulbecco’s Modified Eagle’s Medium under sterile conditions. In the first experiment, two different delivery systems to deliver PDGF - freeze-dried bone allograft and beta- tricalcium phosphate were compared. The second experiment analyzed bone formation in response to BMP-2 in the presence or absence of freeze-dried bone allograft. The media was changed every 2 days and the spent media were analysed for calcium release. At the end of three weeks the calvaria were processed for histological observation, biochemical analyses and neutral red staining. The results show higher bone formation in response to BMP-2 than PDGF. The presence of allograft inhibits this response. We found B-TCP to be a better delivery agent for PDGF compared to freeze-dried bone allograft. The histologic assessment showed development of new bone through intramembranous pathway that replicates native bone development in presence of BMP-2. In conclusion our study proves that incorporation of two bioactive agents- PDGF and BMP-2 in an osteoconductive scaffold can induce repair and new bone formation in mouse calvarial bone cultures. / 2020-07-30T00:00:00Z

No description available.

Uma das complicações mais importantes relacionadas com o tratamento de implante dentário é a peri-implantite. Devido a limitação pela sobreposição de estruturas da técnica periapical, nos casos da perda óssea peri-implantar nas faces vestibulares e linguais ou palatais necessita-se de um exame capaz de prover imagens em 3 dimensões para o correto diagnóstico, sendo as imagens de tomografia computadorizada por feixe cônico (TCFC) as mais indicadas. O objetivo deste estudo foi avaliar a acurácia, especificidade, sensibilidade, concordância inter e intraobservadores e determinar a influência dos artefatos na detecção dos defeitos ósseos peri-implantares simulados em mandíbulas humanas edêndulas secas. Foram utilizados dois aparelhos de TCFC com diferentes protocolos de aquisição: i-CAT Gendex CB-500(120kVp, 5mA) e ORTHOPANTOMOGRAPH OP300(90kVp, 6.3mA). Foram instalados 24 implantes dentários cilíndricos e executados dezesseis defeitos somente nas faces vestibulares, com os comprimentos que variaram de 0,5mm a 15mm. Somente cortes sagitais foram utilizados para avaliação qualitativa e quantitativa dos defeitos foi realizada por meio de Image J. Os resultados do teste de concordância intra e inter-observadores tanto nas avaliações qualitativas e quantitativas foram predominantemente fracos. Os valores de Área Sob a Curva (ASC) variaram de 0.51 a 0.72 no i-CAT Gendex CB-500; e no ORTHOPANTOMOGRAPH OP300 variaram de 0.54 a 0.75, demonstrando desempenho diagnóstico ligeiramente superior. Nas imagens obtidas em aparelho com 120kVp (i-CAT Gendex CB-500) foram observados maior contraste em relação ao aparelho 90kVp (ORTHOPANTOMOGRAPH® OP300); em aparelho com o menor kVp (OP300) formaram mais artefatos e estes, degradaram a qualidade das imagens e influenciaram o desempenho diagnóstico das TCFCs na detecção e nas mensurações de perda óssea peri-implantar. Os protocolos de aquisições diferentes podem influenciar no aumento ou redução da formação dos artefatos. / One of the most important complications related to dental implant treatment is periimplantitis. Due to the structures overlapping inherited to periapical technique, in cases of buccal and lingual or palatal bone loss in peri-implantitis, the 3 dimensions observation exam like cone beam computed tomography(CBCT) is most indicated. The objective of this study was to evaluate the accuracy, specificity, sensitivity, interand intra-observer agreement and to determine the influence of the artifacts in the detection of the peri-implant bone defects simulated in human dry mandibles. The two CBCT devices with different acquisition protocols were used in this study: i-CAT Gendex CB-500 (120kVp, 5mA) and ORTHOPANTOMOGRAPH OP300 (90kVp, 6.3mA). Twenty-four cylindrical dental implants were placed and 16 defects were prepared only on buccal faces, the defect lengths ranged from 0.5mm to 15mm. For qualitative and quantitative assessment, only sagittal slices were evaluated by the observers, using Image J software. The results of intra and inter-observer agreement tests in both assessments were generally poor. The AUC values ranged from 0.51 to 0.72 on the i-CAT Gendex CB-500; and in the ORTHOPANTOMOGRAPH OP300 ranged from 0.54 to 0.75, showing slightly higher diagnostic performance. Higher contrast was observed in the 120 kVp device\'s images (i-CAT Gendex CB-500) when compared with the 90 kVp device\'s image (ORTHOPANTOMOGRAPH® OP300). The low kVp device (OP300), formed more artifacts which degraded the image quality and influenced the CBCT diagnostic performance in the detection and measurement of peri-implant bone loss. Different CBCT acquisition protocols may influence increasing or reducing artefact formation.