Orientador: Wirley Gonçalves Assunção / Resumo: A utilização de biomateriais que visam devolver o volume ósseo perdido após a perda dentária tem se expandido. O osso é um tecido conjuntivo altamente especializado, possuindo dinâmica aposicional onde o equilíbrio entre neoformação e reabsorção envolve a interação de fatores endócrinos, parácrinos e autócrinos. Diversas associações de materiais diversos e substitutos ósseos têm sido estudadas, porém, o MTA (Agregado Trióxido Mineral) ainda carece de informações acerca da sua utilização como substituto ósseo ou em associação com demais substitutos. Assim, o objetivo deste estudo foi avaliar a influência da presença do MTA Angelus Branco® nas proprorções de 5%, 10% e 15% em associação com substituto ósseo de Hidroxiapatita e β- Tricálcio Fosfato na citotoxicidade, resposta tecidual e reparo ósseo, em defeito crítico em calvária de ratos. Para tanto, utilizou-se cultura celular da SAOS-2 para avaliação citológica e ensaio MTT do contato direto e eluentes. Também foram utilizados 112 ratos machos Wistar distribuídos em 7 grupos e avaliados em 2 tempos (7 e 28 dias). Após eutanasiados foram submetidos à microtomografia e por coloração de hematoxilina e eosina para análise histológica e histomorfométrica. A análise da homocedasticidade foi realizada pelo teste Shapiro-Wilk, para distinção dos dados paramétricos e não paramétricos. Para análise dos dados paramétricos, foi realizada análise de variância One-Way (ANOVA One-Way) e realizado o pós-teste de Tukey para os parâmetros micr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The use of biomaterials that aim to return lost bone volume after tooth loss has expanded. Bone is a highly specialized connective tissue with appositional dynamics where the balance between neoformation and resorption involves the interaction of endocrine, paracrine and autocrine factors. Several associations of different materials and bone substitutes have been studied. However, the MTA (Mineral Trioxide Aggregate) still lacks information about its use as bone substitute or in association with other substitutes. Thus, the aim of this study was to evaluate the influence of presence of MTA Angelus Branco® in the 5%, 10% and 15% proportions in association with Hydroxyapatite and β-Tricalcium Phosphate bone substitute in cytotoxicity, tissue response and bone repair in critical defect in rat calvaria. For this, SAOS-2 cell culture was used for cytological evaluation and MTT assay of direct contact and eluents. We also used 112 male Wistar rats distributed into 7 groups and evaluated at 2 distinct times (7 and 28 days). After euthanasia, the specimens were submitted to microtomography and hematoxylin and eosin staining for histological and histomorphometric analysis. The analysis of homoscedasticity was performed by the Shapiro-Wilk test for distinction of parametric and non-parametric data. For analysis of parametric data, one-way analysis of variance (One-Way ANOVA) was performed and Tukey's post-test was performed for the microtomographic parameters and for the cytotoxicity t... (Complete abstract click electronic access below) / Mestre

Orientador: Idelmo Rangel Garcia Júnior / Banca: Francisley Ávila Souza / Banca: André Luís Da Silva Fabris / Resumo: A proposta deste estudo foi avaliar o processo de regeneração óssea com o uso do biomaterial Biogran®, um vidro bioativo, como uma opção de substituto ósseo para técnicas de enxerto em levantamento do assoalho do seio maxilar através de análises histológica e histomorfométrica. Para tal, 24 coelhos da raça Nova Zelândia foram submetidos ao procedimento de levantamento do seio maxilar bilateralmente, sendo divididos em dois grupos: grupo coágulo implante (GCI), no qual foi realizado o levantamento do seio maxilar, seguindo implante imediato, sem enxerto; e o grupo biovidro implante (GBI), no qual foi realizado o levantamento do seio maxilar, preenchimento com Biogran® e instalação de implante imediata. Os animais foram submetidos à eutanásia aos 7, 15 e 40 dias. A análise histológica mostrou no grupo GCI uma formação de tecido ósseo gradual, sendo maior aos 40 dias, com característica lamelar. Porém, não apresentava diferença estatística entre os períodos de 15 e 40 dias de eutanásia (p=0,210). O grupo GBI revelou uma formação de tecido ósseo mais tardia, com maior quantidade aos 40 dias, com reabsorção lenta e progressiva dos grânulos do biomaterial e sinais indicativos de atividade osteoblástica. Este grupo mostrou diferença estatística entre os períodos de 7 e 15 dias quando comparados aos 40 dias (p<0,05). Na análise intergrupos, não houve diferença estatisticamente significante aos 7 e aos 40 dias, mas sim, aos 15 dias. Dessa forma, pode-se concluir que o Biogran® é um bi... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The purpose of this study was to evaluate the bone regeneration process with the use of the Biogran® biomaterial, a bioactive glass, as a bone substitute option for grafting techniques in the maxillary sinus floor through histological and histomorphometric analysis. To that end, 24 New Zealand rabbits underwent a bilateral maxillary sinus removal procedure, and were divided into two groups: an implant clot group (ICG), in which the maxillary sinus was removed, followed by immediate implantation without graft ; and the implant bioglass group (GBI), in which the maxillary sinus was removed, filled with Biogran® and implanted in the immediate implant. The animals were submitted to euthanasia at 7, 15 and 40 days. The histological analysis showed a formation of gradual bone tissue in the GCI group, being larger at 40 days, with a lamellar characteristic. However, there was no statistical difference between the periods of 15 and 40 days of euthanasia (p = 0.210). The GBI group revealed a later bone formation with a greater amount at 40 days, with slow and progressive resorption of the biomaterial granules and signs indicative of osteoblastic activity. This group showed statistical difference between the periods of 7 and 15 days when compared to the 40 days (p <0.05). In the intergroup analysis, there was no statistically significant difference at 7 and 40 days, but at 15 days. Thus, it can be concluded that Biogran® is a biomaterial with osteoconductive properties, of slow resorpt... (Complete abstract click electronic access below) / Mestre

Orientador: Mariza Akemi Matsumoto / Coorientador: Mariza Akemi Matsumoto / Coorientador: Idelmo Rangel Garcia Júnior / Banca: Roberta Okamoto / Banca: André Luís da Silva Fabris / Resumo: Os materiais vítreos podem ser processados por diferentes rotas, dentre elas a convencional por fusão e solidificação ou por rota sol-gel, o que melhora sua bioatividade. O objetivo do presente estudo foi o de avaliar o comportamento biológico da vitrocerâmica Biosilicato® sintetizada pelo processamento sol-gel durante o processo de reparo ósseo em modelo animal. Para tanto, foram utilizados 30 ratos Albinus Wistar, machos, com cerca de três meses de idade e pesando em média 450 gramas. Os mesmos foram submetidos a procedimento cirúrgico para confecção de um defeito de 5mm de diâmetro no osso parietal direito e divididos em 2 grupos, de acordo com o biomaterial estudado: Grupo BS - defeitos preenchidos com Biosilicato® particulado convencional (180-212 µm), e Grupo BG - defeitos preenchidos com Biosilicato® particulado produzido via rota sol-gel (180-212 µm). Após os períodos de 7, 21 e 45 dias, os animais foram submetidos à eutanásia para remoção dos espécimes para serem preparados e submetidos para análise microscópica morfológica e imuno-histoquímica. Aos 7 dias do grupo BS observaram-se partículas do biomaterial circundadas por tecido de granulação, no centro do defeito próximo e tecido ósseo neoformado próximo as suas paredes. Aos 21 dias, presença marcante de CGMs em contato com o biomaterial e aos 45 dias, biomaterial ora substituído por leucócitos MNs e CGMs ora circundado por tecido conjuntivo. Já no grupo BG aos 7 dias observaram-se numerosas partículas arredondadas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The vitreous materials can be processed by different routes, among them the conventional one by fusion and solidification or by route sol-gel, which improves their bioactivity. The objective of the present study was to evaluate the biological behavior of the glass-ceramic Biosilicato® synthesized by sol-gel processing during the bone repair process in animal model. For this, 30 male Albinus Wistar rats were used, about three months old and weighing on average 450 grams. They were submitted to a surgical procedure to make a 5mm diameter defect in the right parietal bone and divided into 2 groups according to the biomaterial studied: BS group - defects filled with conventional particulate biosilicate (180-212 μm), and Group BG - defects filled with particulate Biosilicate® produced via sol-gel route (180-212 μm). After the 7, 21 and 45 day periods, the animals were submitted to euthanasia to remove the specimens to be prepared and submitted for microscopic morphological and immunohistochemical analysis. At 7 days of the BS group biomaterial particles were observed surrounded by granulation tissue, close to the defect wall and noticed if neoformed bone tissue at 21 days, the presence of CGMs in contact with the biomaterial and at 45 days, biomaterial ora replaced by leukocytes MNs and CGMs or surrounded by connective tissue, already in the BG group at 7 days there are numerous rounded biomaterial particles surrounded by granulation tissue at 21 days, presence of CGMs in contact ... (Complete abstract click electronic access below) / Mestre

Orientador: Luana Marotta Reis de Vasconcellos / Coorientadora: Ivone Regina de Oliveira / Banca: Luciane Dias de Oliveira / Banca: Naira Correia Cusma Pelógia / Resumo: O aluminato de cálcio (CAC) como biomaterial tem sido avaliado em relação as suas propriedades físicas, mecânicas e de biocompatibilidade, sendo que suas características únicas de endurecimento e microestrutura, o tornam um biomaterial de destaque. Estudos relataram aplicação destes cimentos na ortopedia visando neoformação óssea devido a sua composição e coeficiente de expansão térmica semelhante ao osso humano. O objetivo neste estudo foi avaliar composições de blendas à base de cimento de aluminato de cálcio homogêneo (CACH) como substitutos em defeitos ósseos. Cinco composições de blendas (alumina, fosfato tricálcico, hidroxiapatita, quitosana, zircônia), além do cimento base CACH e de polimetilmetacrilato (PMMA), totalizando 07 grupos (n=5), foram avaliados quanto à neoformação óssea e formação de biofilme. Foi realizado um defeito ósseo monocortical de 3.0 mm nos fêmures direitos de 35 ratos Wistar, que foram preenchidos aleatoriamente com os materiais acima citados, sendo o grupo de PMMA utilizado como controle. Todos os animais foram eutanasiados após 30 dias a cirurgia. Posteriormente, foi realizada análise por microtomografia computadorizada para verificação da neoformação óssea na interface osso-biomaterial. Para avaliar a formação de biofilmes microbianos monotípicos, discos padronizados com 13,0 x 2,0 mm (n=6) dos 07 cimentos foram confeccionados. Cepas de referência de Staphylococcus aureus, Streptococcus mutans e Pseudomonas aeruginosa foram cultivadas sobre as... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Calcium aluminate as biomaterial has been evaluated for its physical, mechanical and biocompatibility properties. Calcium aluminate based materials exhibit, due to their unique hardening and microstructure characteristics, a great potential as a biomaterial. Studies have reported the application of these cements in orthopedics aimed at bone neoformation due to its composition and coefficient of thermal expansion similar to human bone. Thus, the aim of this study is to evaluate compositions of calcium aluminate cement based blends as substitutes for bone defects. Five compositions of blends (alumina, tricalcium phosphate, hydroxyapatite, chitosan, zirconia), in addition to the base cement consisting of homogeneous calcium aluminate (CACH) and polymethylmethacrylate (PMMA) cement are being evaluated for bone repair and biofilm formation. A monocortical bone defect of 3.0 mm was performed in the right femurs of 35 Wistar rats, these were randomly filled with the already mentioned materials, and the PMMA group was used as control, totaling 07 study groups (n=5). All animals were euthanized within four weeks. Subsequently, a computerized microtomography analysis was performed to verify bone repair. To evaluate the formation of monotypic microbial biofilms, standardized discs with 13.0 x 2.0 mm (n=6) of the seven types of cements evaluated were prepared. Reference strains of Staphylococcus aureus, Streptococcus mutans and Pseudomonas aeruginosa were cultured on the samples and subs... (Complete abstract click electronic access below) / Mestre

Bei der Behandlung der idiopathischen Adoleszentenskoliose werden für die Spondylodese verschiedene Knochenmaterialien verwendet. Das autologe Knochenmaterial wird als der „Goldstandard“ bezeichnet. Da größere Mengen von Knochenmaterial für die Spondylodese nötig sind, erfolgt die Entnahme des autologen Knochens oft auch vom Beckenkamm. Dies kann zu erheblichen Komplikationen führen. Bei der Verwendung von allogenem Material besteht immer die Gefahr der viralen und bakteriellen Kontamination. Aufgrund dieser Probleme besteht ein Interesse an kompatiblen und osteokonduktiven Knochenersatzmaterialien. In dieser Studie soll untersucht werden, ob mit dem Knochenersatzmaterial beta-Tricalciumphosphat in Granulatform eine spinale Fusion erreicht werden kann. Dazu wurden 28 Patienten mit idiopathischer Adoleszentenskoliose nach der Methode von Cotrel-Dubousset operiert. Für die dorsale Spondylodese wurde bei 19 Patienten eine Mischung aus autologem/allogenem Knochen verwendet. 9 Patienten erhielten eine Mischung aus autologem Knochen und 25 g beta-Tricalciumphosphat in Granulatform. Als Verlaufskontrolle wurden zu verschiedenen Zeitpunkten klinische Untersuchungen durchgeführt und Röntgenbilder angefertigt. Zur Beurteilung der Knochendichte wurde bei allen Patienten nach ca. 11 Monaten eine Computertomographie durchgeführt. Eine Fusion der Segmente war bei beiden Gruppen anhand der Röntgenbilder nach ca. 6 Monaten vorhanden. Keine Pseudarthrosen wurden beobachtet. Die Knochendichte war durchschnittlich 430 mg/cm³ in der TCP Gruppe und 337 mg/cm³ in der Knochengruppe. Nach ca. 8 Monaten war das TCP auf den Röntgenbilder nicht mehr nachweisbar. Nach den Ergebnissen zu urteilen, ist beta-Tricalciumphosphat eine gute Alternative bei der operativen Behandlung der idiopathischen Adoleszentenskoliose, mit der ähnliche spinale Fusionsraten, wie mit autologem/allogenem Knochen erreicht werden können, besonders, wenn große Mengen an Knochen benötigt werden. / For correction of idiopathic adolescent scoliosis different bone materials are used to achieve spinal fusion. Autograft bone is known as the gold standard. Mostly large quantities of bone materials are needed for spinal fusion. Autograft bone is often taken from the iliac crest which can lead to severe problems. Using allografts there is always a risk of viral or bacterial contamination. Due to these problems the interest in compatible and osteconductive bone materials is rising. The aim of this study is to evaluate the ability of beta-tricalciumphosphat in granular form to achieve dorsal spondylodesis in adolescent idiopathic scoliosis. 28 patients underwent surgical correction by the method of Cotrel-Dubousset. Posterolateral grafting was performed using autograft/allograft bone for 29 patients and a mixture of autograft bone and 25 g of beta-tricalciumphosphate for 9 patients. As a follow-up clinical examination and X-rays were done at several dates. To measure the bone density CT-scans were taken about 11 month after surgery. According to the radiographs a solid fusion was shown after approximately 6 month in both groups. No pseudarthrosis was observed. Bone mineral density was about 430 mg/cm³ in the TCP group and 337 mg/cm³ in the bone group. After approximately 8 month the TCP was unverifiable in the X-rays. Based on the results of this study beta-tricalciumphosphate can be seen as an alternative in the surgical correction of idiopathic adolescent scoliosis. Similar spinal fusion rates compared with the use of autograft/allograft bone can be achieved, especially when huge quantities of bone are needed.

Calcium phosphate cements are produced by the mixing of calcium phosphate powders in an aqueous solution resulting in a low-temperature synthesized hydroxyapatite. They have been used as bone substitutes and drug delivery systems. The present work examined the possibility of a machine-based modification to this process to derive a standardized preparation method of calcium phosphate cements that could be loaded with Pantoprazole. To examine the characteristics of these novel materials, the following analyses of hand- and machine-made cements, with and without Pantoprazole were undertaken: in vitro surface characterization, dissolution, hydroxyapatite conversion, Pantoprazole delivery, as well as in vivo reparative bone formation and particulate degradation. The in vitro surface characterization, dissolution at different pHs, and drug release analyses showed insignificant differences between hand- and machine-prepared cements. However, machine-made cements showed increased hydroxyapatite conversion, decreased dissolution at pH 7.4, and better in vivo outcomes than commercially available bone-substitute particulate biomaterials.

The need for an alternative to red cells in transfusions has led to the creation of hemoglobin-based oxygen carriers (HBOCs). However, evaluations of all products tested in clinical trials have noted cardiovascular complications, raising questions about their safety that led to the abandonment of all those products. It has been considered that the adverse side effects come from the scavenging of the vasodilator – nitric oxide (NO) by the deoxyheme sites of the hemoglobin derivatives. Another observation is that HBOCs with lower oxygen affinity than red cells release oxygen prematurely in arterioles, triggering an unwanted homeostatic response. Since the need for such a product remains critical, it is important to understand the reactivity patterns that contribute to the observed complications. Various alterations of the protein have been attempted in order to reduce HBOC-induced vasoconstriction. Recent reports suggest that a safe and effective product should be pure, homogenous and have a high molecular weight along with appropriate oxygenation properties. While these properties are clearly important, vasodilatory features of hemoglobin through its nitrite reductase activity may also act as an in situ source of NO. It follows that HBOCs with an enhanced ability to produce NO from endogenous nitrite may serve to counteract vasoactivity associated with NO-scavenging by hemoglobin. Here we characterize the effects of different protein modifications on the nitrite reductase activity of hemoglobin. We produced a variety of HBOCs that include cross-linked tetramers, polyethylene glycol (PEG) conjugates and bis-tetramers of hemoglobin. We report that the rate of NO production strongly depends on the conformational state of the protein, with R-state stabilized proteins (PEG-Hbs), exhibiting the fastest rates. In particular, we found that PEGylated bis-tetramers of hemoglobin (BT-PEG) exhibit increased nitrite reductase activity while retaining cooperativity and stability. Animal studies of BT-PEG demonstrated that this material is benign: it did not cause significant increases in systemic blood pressure in mice, the major side effect associated with existing HBOCs. BT-PEG exhibits an enhanced nitrite reductase activity together with sample purity and homogeneity, molecular size and shape, and appropriate oxygenation properties, characteristics of a clinically useful HBOC.

Calcium phosphate cements are produced by the mixing of calcium phosphate powders in an aqueous solution resulting in a low-temperature synthesized hydroxyapatite. They have been used as bone substitutes and drug delivery systems. The present work examined the possibility of a machine-based modification to this process to derive a standardized preparation method of calcium phosphate cements that could be loaded with Pantoprazole. To examine the characteristics of these novel materials, the following analyses of hand- and machine-made cements, with and without Pantoprazole were undertaken: in vitro surface characterization, dissolution, hydroxyapatite conversion, Pantoprazole delivery, as well as in vivo reparative bone formation and particulate degradation. The in vitro surface characterization, dissolution at different pHs, and drug release analyses showed insignificant differences between hand- and machine-prepared cements. However, machine-made cements showed increased hydroxyapatite conversion, decreased dissolution at pH 7.4, and better in vivo outcomes than commercially available bone-substitute particulate biomaterials.

The need for an alternative to red cells in transfusions has led to the creation of hemoglobin-based oxygen carriers (HBOCs). However, evaluations of all products tested in clinical trials have noted cardiovascular complications, raising questions about their safety that led to the abandonment of all those products. It has been considered that the adverse side effects come from the scavenging of the vasodilator – nitric oxide (NO) by the deoxyheme sites of the hemoglobin derivatives. Another observation is that HBOCs with lower oxygen affinity than red cells release oxygen prematurely in arterioles, triggering an unwanted homeostatic response. Since the need for such a product remains critical, it is important to understand the reactivity patterns that contribute to the observed complications. Various alterations of the protein have been attempted in order to reduce HBOC-induced vasoconstriction. Recent reports suggest that a safe and effective product should be pure, homogenous and have a high molecular weight along with appropriate oxygenation properties. While these properties are clearly important, vasodilatory features of hemoglobin through its nitrite reductase activity may also act as an in situ source of NO. It follows that HBOCs with an enhanced ability to produce NO from endogenous nitrite may serve to counteract vasoactivity associated with NO-scavenging by hemoglobin. Here we characterize the effects of different protein modifications on the nitrite reductase activity of hemoglobin. We produced a variety of HBOCs that include cross-linked tetramers, polyethylene glycol (PEG) conjugates and bis-tetramers of hemoglobin. We report that the rate of NO production strongly depends on the conformational state of the protein, with R-state stabilized proteins (PEG-Hbs), exhibiting the fastest rates. In particular, we found that PEGylated bis-tetramers of hemoglobin (BT-PEG) exhibit increased nitrite reductase activity while retaining cooperativity and stability. Animal studies of BT-PEG demonstrated that this material is benign: it did not cause significant increases in systemic blood pressure in mice, the major side effect associated with existing HBOCs. BT-PEG exhibits an enhanced nitrite reductase activity together with sample purity and homogeneity, molecular size and shape, and appropriate oxygenation properties, characteristics of a clinically useful HBOC.

"Substitutes for leadership" is a new emerging leadership model of organizations within turbulent environments. Employee might minimize the "need for leadership" by "shared values", "self-managed work teams" and "cynicism". These substitutes would have further direct impacts on job outcomes as well. This study suggests that the higher the extent of shared values, self-managed work teams or cynicism, the lower the extent of the need for leadership. Also except cynicism, the higher the extent of shared values or self-managed work teams, the higher the extent of job outcomes. Data used were collected in two Kaohsiung companies, including an insurance agent and a semiconductor company. After statistic analyzes the results are stated as bellow: ¢¹. Differences of all variables due to characteristics of individuals. 1. The insurance agent: Employee are graduated from senior high schools have the higher extents of job outcomes than those are graduated from colleges. Sales have the higher extent of shared values, self-managed work teams and job outcomes, and the lower extent of cynicism than clerks. 2. The semiconductor company: No characteristics of individuals make a difference of variables. ¢º. Relationships between substitutes and the need for leadership. 1. The insurance agent: The higher the extent of shared values the higher the extent of the need for leadership. The higher the extent of self-managed work teams the higher the extent of the need for leadership. The higher the extent of cynicism the higher the extent of the need for leadership. 2. The semiconductor company: The same as the above. ¢». Relationships between substitutes and job outcomes. 1. The insurance agent: The higher the extent of shared values, the higher the extent of job outcomes; the higher the extent of self-managed work teams, the higher the extent of job outcomes; the lower the extent of cynicism, the higher the extent of job outcomes. 2. The semiconductor company: The same as the above. The empirical results show that although the substitutes regression model can offer explanation of job outcomes, the higher extents of shared values and self-managed work teams do not lead to the lower extent of the need for leadership. The reason that hypotheses are not approved seems to be the sampling. The insurance agent is an organization of the tight leader-follower relationship; the subordinators of the newly established semiconductor company of course strongly depend on the experienced leaders. Or shared values and self-managed work teams would not be the substitutes for leadership in deed. Or leadership could not be replaced at all!