Because of its high specific strength, durability, and biocompatibility, titanium is a widely used material for orthopedic implants. However, its insufficient binding with the surrounding bone tissue regularly leads to stress shielding, bone resorption and implant loosening. A promising solution to improve adhesion is to modify the implant surface chemistry and topography by coating it with a protein-eluting polyelectrolyte complex. Bone morphogenetic protein 2 (BMP-2), a potent osteoconductive growth factor, was adsorbed onto the surface of anodized titanium, and polyelectrolyte multilayer (PEM) coatings prepared from solutions of poly-L-histidine (PLH) and poly(methacrylic acid) (PMAA) were built on top of the BMP-2. The effect of solution pH during the deposition process was investigated. High levels of BMP-2 released over several months were achieved. Approximately 2 μg/cm² of BMP-2 were initially adsorbed on the anodized titanium and a pH-dependent release behavior was observed, with more stable coatings assembled at pH = 6-7. Three different diffusion regimes could be determined from the release profiles: an initial burst release, a sustained release regime and a depletion regime. Mass adsorption monitoring using quartz crystal microbalance with dissipation monitoring (QCM-D) showed that PLH was adsorbed in greater quantities than PMAA, and that more mass was adsorbed per bilayer as the number of bilayers grew. Moreover, the pH of the water used during the rinsing step significantly impacted the composition of the multilayer. Atomic force microscopy (AFM) and contact angle analysis (CAA) were used to determine the topography and surface energy of the PEMs. No visible change was observed in surface morphology as the assembly pH was varied, whereas the surface energy decreased for samples prepared at more basic pH. These variations indicate that the influence of the initial BMP-2 layer can be felt throughout the PEM and impact its surface structure.

O propósito deste trabalho foi avaliar a interação de matriz óssea bovina inorgânica, (Gen-ox®) como material de enxerto e implantes de titânio em mandíbula de coelhos. A amostra constituiu-se de 32 coelhos da raça Botucatu de aproximadamente 4kg. Os incisivos inferiores destes animais foram extraídos e foi realizada um defeito de aproximadamente 4mm de diâmetro. Um dos lados foi mantido apenas com coágulo (grupo controle) e o outro lado (grupo experimental) recebeu o enxerto do material proposto. Após 60 dias foram instalados implantes bilateralmente na região do defeito. Os animais foram eutanaziados imediatamente após a instalação dos implantes e após 1, 2 e 6 meses (n=6) para o grupo microscópico a após 2 e 6 meses para o grupo do teste biomecânico (n=4). A análise constituiu de medidas da distância da crista óssea alveolar à plataforma do implante, da densidade radiográfica em valores de pixel ma região do alvéolo, de teste biomecânico de torque de remoção e microscópico através de medidas de contato osso-implante (BIC) (em µm e %) e área de osso (em µm2 e %). Os resultados demonstraram que não houve diferenças significantes nem durante o tempo e nem entre os grupos na analise de distancia entre crista óssea alveolar e plataforma do implante. Na medida de densidade óssea, não houve variação significante ao longo do tempo, mas houve diferença estatisticamente significante entre os grupos, sendo maior no grupo experimental. Para o teste biomecânico também não houve variação significante do torque de remoção ao longo do tempo e nem houve diferença significante entre os grupos. Na análise de contato osso implante (BIC) não houve variação significante ao longo do tempo, mas houve diferença estatisticamente significante entre os grupos, sendo maior no grupo experimental e houve interação entre tempos e grupos. E com relação a medida de área de osso não houve diferenças significantes nem durante o tempo e nem entre os grupos controle e experimental nos períodos analisados. Os resultados sugerem que o material foi bem aceito na região e teve comportamento semelhante ao coágulo em contato com a superfície do implante. / The aim of this study was to evaluate the interaction of an inorganic bovine bone matrix (Gen-ox®) as bone graft and titanium implants in rabbits mandible. Thirty-two Botucatu rabbits weighting about 4kg were used on this experiment. The mandible incisives were extracted and a defect of 4 mm of diameter was performed. One socket and defect was filled with experimental material. The opposite site was left to heal naturally and served as control. After 60 days, the implants were installed on the defect region. The animals were killed immediately after the implant installation and after 1, 2 and 6 months. Vertical bone height, bone density, biomechanical test, bone implant contact (BIC) and bone area near to implant threads were evaluated. The results showed that there was no significant differences on the distance between the alveolar bone crest to the implant platform (vertical bone height) along the time, neither between groups. On the bone density (pixel value) there was no significant difference along the time, but there was significant difference between groups, being the experimental group higher. For the biomechanical test there was no significant difference along the time, neither between groups. There was no significant differences on the bone implant contact (BIC) measures along the time, but there was significant difference between groups, being the experimental groups higher and there was interaction between time and groups. On bone area evaluation, there was no significant difference along the time, neither between the groups during the analyzed time. The graft behavior observed by the authors was similar to that of the control group, suggesting high acceptance of the material as graft option associated to titanium implants.

Made available in DSpace on 2017-07-24T19:22:04Z (GMT). No. of bitstreams: 1 Micheleelias.pdf: 598764 bytes, checksum: 189fdf6d0d1c8583d61adb9e336c15cf (MD5) Previous issue date: 2008-02-19 / Similar to natural teeth, implants are liable to destruction of support structures. This process of destruction is often the result of opportunistic infections by bacteria that colonizes restorations on the implants and adjacent theeth. A. actinomycetemcomitans is often isolated from periodontal and periimplantar sites but its hole in disease is already to be determined. The aim of this study was to compare the presence of A. actinomycetemcomitans in samples of crevicular fluid and saliva from 14 patients partially and 8 totally edentulous, aging from 42 to 78 years old, rehabilitated with osseointegrated titanium implants, Samples of crevicular fluid were obtained with paper points introduced in periimplantar pockets after removal of supragingival plaque with sterile gauze and left inside for 1 minute. The poits were transferred to tubes with triptic soy solution, homogeneized and plated, in duplicate, on TSBV agar and the plates incubated for 5 days in 37C. After this period, the number of cfu/mL of the microorganism. The presence of A. actinomycetemcomitans was also verified in samples of saliva. The samples were collected with sterile swabs and processed the same way. The results demonstrated that A. actinomycetemcomitans is isolated from gingival fluid and saliva in a small number of patients and in small quantity, both in partially edentulous and totally ones and the differences were not significant between groups (Test Mann-Whitney-gingival fluid: 0.7280; saliva: 0.3503). the results of this study suggest that the colonization of periimplantar sulcus and oral cavity of and the number of mL of A. actinomycetemcomitans in theses sites are not modulated by the presence or not natural theeth. / Semelhante aos dentes, os implantes são susceptíveis à destruição de estruturas de suportes. Este processo de destruição é com freqüência o resultado de infecções por bactérias oportunistas que colonizaram a restauração sobre o implante e a dentição adjacente. Aggregatibacter actinomycetemcomitans é frequentemente isolado de sítios periodontais e periimplantares, entretanto os fatores que modulam a colonização da mucosa bucal e o papel deste microrganismo na doença são controversos. Assim, o objetivo deste estudo foi comparar a presença de A. actinomycetemcomitans em amostras de fluido gengival periimplantar e saliva de 14 pacientes parcialmente edêntulos e 8 totalmente edêntulos, com idade entre 42 e 78 anos, reabilitados com implantes osseointegrados de titânio. Amostras do fluido gengival foram obtidas com cones de papel que foram introduzidos nos sulcos periimplantares após remoção do biofilme supragengival com gaze esterilizada e deixados por um minuto. Os cones foram transferidos para solução de caldo tripticaseína de soja, homegeneizados e as amostras foram semeados em duplicata em agar TSBV - ágar de soja tripticaseína acrescido de bacitracina e vancomicina, e incubadas a 37C por cinco dias em anaerobiose (Anaerobac). Após incubação, determinou-se o número de mL do microrganismo pesquisado. A. actinomycetemcomitans também foi pesquisado na saliva, que foi coletada com auxilio de suabes esterilizados e processada microbiologicamente do mesmo modo que as amostras obtidas da região periimplantar. Os resultados mostraram que não houve diferença estatística, demonstrada através do teste Mann-Whitney, no número de mL de A. actinomycetemcomitans, tanto na saliva quanto no fluido do sulco periimplantar, quando comparou-se os pacientes totalmente desdentados e parcialmente desdentados (sulco: 0.7280; saliva 0.3503). Os resultados obtidos sugerem que a colonização do sulco periimplantar e cavidade bucal e o número de A. actinomycetemcomitans nesses sítios não são modulados pela presença ou não de dentes naturais.

Osseointegration, or the direct integration of an implant into bone tissue, is necessary for implant success. Titanium is commonly used clinically in dental and orthopaedic implants because of its passivating oxide layer, which facilitates osseointegration, and its mechanical properties such as a modulus of elasticity similar to bone. Diverse studies have shown that surface microtopography, chemistry, and surface energy affect osteoblast behavior. The problem with these studies is that they access the average behavior of a culture in response to a substrate and not the behavior of individual cells. The objective of this study was to develop a method for correlating the behavior of individual cells with the characteristics of the surface underneath them. More specifically, this work developed a method to correlate integrin beta-1 (β1) expression with the surface characteristics under individual cells. Integrins are cell surface receptors that bind to specific proteins in the extracellular matrix adsorbed on the implant surface. Previous work has shown that expression of certain integrins is increased when osteoblasts on titanium substrates develop a more differentiated phenotype, and that integrin β1 is necessary for osteoblast response to roughness on titanium substrates. This study used molecular beacons specific to integrin β1 to quantify integrin β1 expression of MG63 cells cultured on titanium disks. A template was designed to coordinate the location of cells using fluorescence microscopy and scanning electron microscopy (SEM) in reference to laser etchings on the disks. After live cell imaging, cells were fixed, dried, and critical point dried for focused ion beam (FIB) milling. Transmission electron microscopy (TEM) sections of cells identified with high and low integrin β1 molecular beacon intensity were milled, and cells with high and low integrin β1 molecular beacon intensity were also serial sectioned. While our TEM results were inconclusive, SEM images from serial sectioning showed contact points between the cell body and the substrate, consistent with previous results. Cells cultured on pretreatment (PT) or sandblasted acid etched (SLA) titanium surfaces were also serial sectioned, showing that cells on SLA surfaces have more regions of contact between the cells and the substrate than cells on PT surfaces. This work is significant as it is the first study to develop a method to correlate individual cell behavior with the substrate surface characteristics under the individual cells. Previous studies have reported the average cell behavior in response to their substrates, while this work allows for the study of substrate surface characteristics that positively affect integrin β1 expression in individual cells. Further optimization of the fluorescence imaging process and FIB milling process could be done, and the method developed in this study could be used in future studies to investigate surface characteristics after using other fluorescent analyses of cell behavior, such as immunocytochemistry.

Biomaterial surface properties such as microtopography and energy can change cellular responses at the cell-implant interface. Phospholipase D (PLD) is required for differentiation of osteoblast-like MG63 cells on machined and grit-blasted titanium surfaces. Here, we determined if PLD is also required on microstructured/high-energy substrates and the mechanism involved. shRNAs for human PLD1 and PLD2 were used to silence MG63 cells. Wild-type and PLD1 or PLD1/2 silenced cells were cultured on smooth-pretreatment surfaces (PT); grit-blasted, acid-etched surfaces (SLA); and SLA surfaces modified to have higher surface energy (modSLA). PLD was inhibited with ethanol or activated with 24,25-dihydroxyvitamin-D₃ [24R,25(OH)₂D₃]. As surface roughness/energy increased, PLD mRNA and activity increased, cell number decreased, osteocalcin and osteoprotegerin increased, and protein kinase C (PKC) and alkaline phosphatase specific activities increased. Ethanol inhibited PLD and reduced surface effects on these parameters. There was no effect on these parameters after knockdown of PLD1, but PLD1/2 double knockdown had effects comparable to PLD inhibition. 24R,25(OH)₂D₃increased PLD activity and production of osteocalcin and osteoprotegerin, but decreased cell number on the rough/high-energy surfaces. These results confirm that surface roughness/energy-induced PLD activity is required for osteoblast differentiation and that PLD2 is the main isoform involved in this pathway. Here we showed that PLD is activated by 24R,25(OH)₂D₃ in a surface-dependent manner and inhibition of PLD reduced the effects of surface microstructure/energy on PKC, suggesting that PLD mediates the stimulatory effect of microstructured/high-energy surfaces via PKC-dependent signaling.

Dental and orthopaedic implants are currently the solutions of choice for teeth and joint replacements with success rates continually improving, but they still have undesirable failure rates in patients who are compromised by disease or age, and who in many cases are the ones most in need. The success of titanium (Ti) implants depends on their ability to osseointegrate with the surrounding bone and this, in turn, is greatly dependent on the surface characteristics of the device. Advancements in surface analysis and surface modification techniques have improved the biological performance of metallic implants by mimicking the hierarchical structure of bone associated with regular bone remodeling. In this process, damaged bone is resorbed by osteoclasts, which produce resorption lacunae containing high microroughness generated after mineral dissolution under the ruffled border, as well as superimposed nanoscale features created by the collagen fibers left at the surface. Indeed, increasing Ti surface roughness at the micro and sub-microscale level has been shown to increase osteoblast differentiation in vitro, increase bone-to-implant contact in vivo, and accelerate healing times clinically. Recently, the clinical application of surface nanomodification of implants has been evaluated. Still, most clinically-available devices remain smooth at the nanoscale and fundamental questions remain to be elucidated about the effect of nanoroughness on the initial response of osteoblast lineage cells. Another property that could be used to control osteoblast development and the process of osseointegration is the electrical surface charge of implants. The presence of endogenous electrical signals in bone has been implicated in the processes of bone remodeling and repair. The existence of these native signals has prompted the use of external electrical stimulation to enhance bone growth in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports confirming its beneficial effects on bone formation. However, the use of electrical stimulation on Ti implants to enhance osseointegration is less understood, in part because of the lack of in vitro models that truly represent the in vivo environment. In addition, an aspect that has not been thoroughly examined is the electrical implication of implant corrosion and its effect on the surrounding tissue. Implants are exposed to extreme conditions in the body such as high pH during inflammation, and cyclic loads. These circumstances may lead to corrosion events that generate large electrochemical currents and potentials, and may cause abnormal cell and tissue responses that could be partly responsible for complications such as aseptic loosening of implants. Consequently, Ti implants with tailored surface characteristics such as nanotopography and electrical polarization, could promote bone healing and osseointegration to ensure successful outcomes for patients by mimicking the biological environment of bone without the use of systemic drugs. The objective of this thesis is to understand how surface nanostructural and electrical characteristics of Ti and Ti alloy surfaces may affect osteoblast lineage cell response in vitro for normal tissue regeneration and repair. Our central hypothesis is that combined micro/nanostructured surfaces, as well as direct stimulation of Ti surfaces with fixed direct current (DC) potentials, can enhance osteoblast differentiation.

Submitted by FERNANDA HERRERA DA COSTA (ferherreracosta@gmail.com) on 2018-05-24T14:02:59Z No. of bitstreams: 1 dissertação final.pdf: 14796170 bytes, checksum: b56cc2f9884a2482b189d839e1ebdcca (MD5) / Approved for entry into archive by Silvana Alvarez null (silvana@ict.unesp.br) on 2018-06-06T19:33:04Z (GMT) No. of bitstreams: 1 godoi_fhc_me_sjc.pdf: 14796170 bytes, checksum: b56cc2f9884a2482b189d839e1ebdcca (MD5) / Made available in DSpace on 2018-06-06T19:33:04Z (GMT). No. of bitstreams: 1 godoi_fhc_me_sjc.pdf: 14796170 bytes, checksum: b56cc2f9884a2482b189d839e1ebdcca (MD5) Previous issue date: 2018-03-26 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A sobrevida de pacientes submetidos a tratamentos para câncer de cabeça e pescoço está aumentando e a busca por reabilitação é necessária para promover qualidade de vida. O objetivo deste estudo é avaliar o perfil da expressão gênica de transcritos relacionados na osteogênese e osteoclastogênese em uma cultura primária de células mesenquimais de fêmures de ratos submetidos a radioterapia e colocação de implantes de titânio. Setenta e dois ratos receberam implantes de titânio em ambos fêmures. Os animais foram divididos em quatro grupos: 1) Grupo controle (C): cirurgia de colocação dos implantes; 2) Implante + irradiação imediata (IrI): irurgia de implantes e seguido de irradiação imediata; 3) Implante + irradiação tardia (IrT): cirurgia de implantes e irradiação após 4 semanas; 4) Irradiação prévia + implantes (IrP): irradiação e após 4 semanas cirurgia de implantes. A dose de irradiação foi de 30 Gy fracionadas em duas sessões. As eutanásias nos períodos de 3, 14 e 49 dias após o tratamento. A células cultivadas sofreram diferenciação em osteoblastos. A expressão gênica dos genes Fosfatase alcalina (Alp), Colágeno 1 (Col-1), Integrina !1 (Itg ! ), Osteocalcina (Bglap), Osteopontina (Osp), Osteonectina (Osn), Sialoproteína Óssea (Bsp), Fator de crescimento transformador (Tgf- ! ), Osterix (Osx),Fator relacionado ao Runt (Runx2), Fator estimulador de colônias de macrófagos (M-csf), Interleucina -6 (Il-6) Apolipoproteína E (Apo-E), Prostaglandina E2 (PgE2), foram avaliados por qRT-PCR e os resultados validados por ELISA. A expressão mais alta de Alp foi encontrada no grupo IrP (p=0.0001) e foi subexpressa nos grupos IrI e IrT (p<0.0001 e p=0.0041 respectivamente). Resultados similares foram encontrados nos transcritos de Itg !, On, Bsp, Osx e Runx2. mRNA do Tgf- ! foi hiperexpresso em todos os grupos principalmente aos 49 dias. Depois de 49 dias, os níveis de proteína da Bglap e Il-6 foram correlacionados com a expressão do mRNA. A radioterapia imediata altera a atividade de diferenciaçãO das células mesenquimais dos fêmures de ratos. / Prognosis of patient submitted to head and neck cancer treatment has increased and the oral rehabilitation becomes necessary to improve their life quality. The aim of this study was to evaluate the gene expression profile of transcripts related to osteogenesis and osteoclastogenesis in primary culture of mesenchymal cells from rat femurs submitted to radiotherapy and installation of pure titanium implant. Seventy two rats received titanium implants in both femurs. The animals were divided in four groups: 1- Control (C) implant surgery; 2- Implant + immediate irradiation after 24 hours (IrI); 3- Implant + late irradiation after 4 weeks (IrL); 4- Implant + Previous irradiation 4 weeks before surgery (IrP) irradiation. The irradiation dose was 30Gy fractioned in two. The animals were euthanized in day 3, 14 and 49 after surgery. The mesenchymal cells from femurs were extracted and cultivated. The differentiation into osteoblastic cells was verified by calcification nodules formation. The gene expression of Alkaline Phosphatase (Alp), Collagen 1 (Col 1), Integrin β1 (ItgB1), Osteocalcin (Bglap), Osteopontin (Osp), Osteonectin (Osn), Bone Sialoprotein (Bsp), Transforming Growth Factor β-type (Tgf-β), Osterix (Osx), Runt-related transcription factor 2 (Runx2), Macrophage Colony- Stimulating Factor (M–csf), Interleukin-6 (Il-6), Apolipoprotein E (ApoE) and Prostaglandin E2 (PgE2) were evaluated by qRT-PCR and the results were validated by ELISA test. Higher mRNA of Alp expression was found in IrP group (p=0.0001) and it was downregulated in IrI and IrT groups (p<0.0001 and p=0.0041, respectively). Similar results were found for transcript levels of ItgB1, Osn, Bsp, Osx and Runx2. mRNA of Tgf-β was overexpressed in all groups mainly in 49 days. After 49 days, Osn and Bsp transcripts were downregulated in the 3 groups evaluated. The Bglap and IL-6 protein level was correlated to their mRNA expression. The radiotherapy alters immediately the differentiation and activity of mesenchymal cells from rat femurs; however these cells seem to recover becoming suitable for receiving implants. / FAPESP: 2016/20103-7

O propósito deste trabalho foi avaliar a interação de matriz óssea bovina inorgânica, (Gen-ox®) como material de enxerto e implantes de titânio em mandíbula de coelhos. A amostra constituiu-se de 32 coelhos da raça Botucatu de aproximadamente 4kg. Os incisivos inferiores destes animais foram extraídos e foi realizada um defeito de aproximadamente 4mm de diâmetro. Um dos lados foi mantido apenas com coágulo (grupo controle) e o outro lado (grupo experimental) recebeu o enxerto do material proposto. Após 60 dias foram instalados implantes bilateralmente na região do defeito. Os animais foram eutanaziados imediatamente após a instalação dos implantes e após 1, 2 e 6 meses (n=6) para o grupo microscópico a após 2 e 6 meses para o grupo do teste biomecânico (n=4). A análise constituiu de medidas da distância da crista óssea alveolar à plataforma do implante, da densidade radiográfica em valores de pixel ma região do alvéolo, de teste biomecânico de torque de remoção e microscópico através de medidas de contato osso-implante (BIC) (em µm e %) e área de osso (em µm2 e %). Os resultados demonstraram que não houve diferenças significantes nem durante o tempo e nem entre os grupos na analise de distancia entre crista óssea alveolar e plataforma do implante. Na medida de densidade óssea, não houve variação significante ao longo do tempo, mas houve diferença estatisticamente significante entre os grupos, sendo maior no grupo experimental. Para o teste biomecânico também não houve variação significante do torque de remoção ao longo do tempo e nem houve diferença significante entre os grupos. Na análise de contato osso implante (BIC) não houve variação significante ao longo do tempo, mas houve diferença estatisticamente significante entre os grupos, sendo maior no grupo experimental e houve interação entre tempos e grupos. E com relação a medida de área de osso não houve diferenças significantes nem durante o tempo e nem entre os grupos controle e experimental nos períodos analisados. Os resultados sugerem que o material foi bem aceito na região e teve comportamento semelhante ao coágulo em contato com a superfície do implante. / The aim of this study was to evaluate the interaction of an inorganic bovine bone matrix (Gen-ox®) as bone graft and titanium implants in rabbits mandible. Thirty-two Botucatu rabbits weighting about 4kg were used on this experiment. The mandible incisives were extracted and a defect of 4 mm of diameter was performed. One socket and defect was filled with experimental material. The opposite site was left to heal naturally and served as control. After 60 days, the implants were installed on the defect region. The animals were killed immediately after the implant installation and after 1, 2 and 6 months. Vertical bone height, bone density, biomechanical test, bone implant contact (BIC) and bone area near to implant threads were evaluated. The results showed that there was no significant differences on the distance between the alveolar bone crest to the implant platform (vertical bone height) along the time, neither between groups. On the bone density (pixel value) there was no significant difference along the time, but there was significant difference between groups, being the experimental group higher. For the biomechanical test there was no significant difference along the time, neither between groups. There was no significant differences on the bone implant contact (BIC) measures along the time, but there was significant difference between groups, being the experimental groups higher and there was interaction between time and groups. On bone area evaluation, there was no significant difference along the time, neither between the groups during the analyzed time. The graft behavior observed by the authors was similar to that of the control group, suggesting high acceptance of the material as graft option associated to titanium implants.

Bone formation and bone healing were studied in the mandible, tibia and skull bones in adult, healthy and estrogen deficient rabbits implanted with different bone substitutes. In the first study an evaluation of the differences in bone regeneration in and around solid (Alveograf *) and porous hydroxyapatite (Interpore 200*) was undertaken. The implant material was placed into experimentally made bone defects and in half of the defects hydroxyapatite was mixed with a fibrin sealant (Tisseel *). The material alone or mixed with Tisseel was also placed subperiostally in the mandible. The observation time was six month. No difference in bone regeneration was found between solid or porous hydroxyapatite granulas and the addition of Tisseel* did not seem to disturb the bone healing process. The implant material placed subperiostally did not induce bone formation nor did it provoke any bone resorption. The addition of Tisseel made the implant material much easier to handle and retain in the tissue during surgery. Bone healing around hydroxyapatite implants was also evaluated in the second study. Experimental cavities in the mandible and tibia were filled with hydroxyapatite in granules or blocks (Interpore 200*) but now with or without autolyzed, antigen-extracted, allogeneic bone (AAA). Also in this study Tisseel* was used to facilitate the handling of the material. All cavities implanted with AAA-bone, regardless of the combination with hydroxyapatite or Tisseel, demonstrated excessive bone formation resembling exostosis formation. Thus, hydroxyapatite, both as granules and blocks, can be successfully combined with AAA bone utilizing the bone inductive capacity of AAA bone. The same model was used to study the healing in ovariectomized animals in the third study. Bone cavities were implanted with or without AAA bone and left to heal. The results indicate that the osteoinductive capacity of AAA bone is in operation also in animals deprived of a normal estrogen production. The effect of using AAA bone prior to implant insertion was studied in paper four. The bone-implant contact was significant higher when AAA bone had been used. The implant stability did not seem to be affected. In paper five defects were made in skull and tibial bone in estrogen deficient animals. The deficiency of estrogen was confirmed through blood analysis, the decrease in the weight of uterus and bone mineral density. The whole body scanning with DEXA showed that the ovariectomized animals developed osteopenia. Various degree of bone formation was seen in the defects due to the influence of the bone inductive substance AAA bone. The studies indicate that a conductive material like hydroxyapatite in granules or blocks could be useful in oral reconstructive surgery. The combination with AAA bone enhanced the bone formation in calvarial and tibial bone in healthy and estrogen deficient animals. Tisseel* could be used to facilitate handling and retention of the material in the intended position during the healing process without negative effects.

Durante a confecção do alvéolo, promove-se o aumento da temperatura da broca devido à fricção, aquecendo o tecido ósseo adjacente e seus componentes celulares, podendo provocar a Necrose Óssea Térmica. A necrose óssea térmica deteriora a porção orgânica do tecido ósseo (tanto matriz óssea como as células), bem como as células diferenciadas e indiferenciadas presentes na circulação sanguínea e medula óssea local. Alguns trabalhos demonstraram que o aquecimento ósseo acima de 47oC por 1 minuto provoca tal fenômeno. Atualmente existem variações na técnica de perfuração com objetivo de diminuir o grau de aquecimento e aumentar as taxas de sucesso dos tratamentos reabilitadores. Sabemos que nem todos os profissionais são cautelosos em utilizar materiais de qualidade e que mesmo os materiais com qualidade, após repetido uso, perdem a eficácia. Seria ideal que o implante osseointegrável gerenciasse a remoção destas áreas de necrose óssea térmica, independentemente da execução correta da técnica de perfuração e da qualidade das brocas. Com isso, garantiríamos que o tecido ósseo poderia se reparar ao redor dos implantes da melhor maneira possível. Neste trabalho avaliamos a eficácia de 3 modelos de implante com câmaras coletoras funcionais diferentes, em tecido ósseo de minipig. O implante com câmara coletora interna demonstrou-se 37,22% mais eficaz que o implante com câmaras externas e 3 arestas cortantes, quando os alvéolos eram confeccionados sem irrigação e com brocas desgastadas. O implante com câmaras coletoras externas e 4 arestas também demonstrou-se eficaz, porém manteve 83,75% das células viáveis enquanto que no grupo com câmaras internas este resultado foi de 91,39%. / The manufacture of the alveolus can increase the temperature of the drill due to friction heating the adjacent bone tissue and its cellular components, this phenomenon is known by thermal osteonecrosis. The thermal osteonecrosis deteriorates the organic portion of bone (bone matrix and cells), as well as undifferentiated and differentiated cells circulating in the blood and bone marrow. Some studies have demonstrated that bone heating above 47oC for 1 minute causes this phenomenon. Currently there are variations in drilling technique aiming to reduce the heating degree and increase the success rates of rehabilitation treatments. We know that not all professionals are cautious of using quality materials and even the materials with quality after repeated use, lose their effectiveness. Would be ideal that implants manages and removes these areas with thermal osteonecrosis, regardless of the technique of implementing the drilling and the quality of drills. With this, we ensure that bone tissue could possibly repair around implants in the best way. In this study we evaluated the efficacy of 3 implant models with different functional collecting chambers in minipigs bone tissue. The implant with internal collection chamber proved to be 37.22% more effective than the implant with external chambers and three sharp edges, when the alveolus were manufactured without irrigation and uncut drills. The implant with external collecting chambers and four sharp edges also showed an effective but 83.75% of the cells remained viable while in the group with internal chambers this result was 91.39%.