Made available in DSpace on 2015-03-26T13:47:13Z (GMT). No. of bitstreams: 1 texto completo.pdf: 2356825 bytes, checksum: d31053454fc83d68df0097e746529fd9 (MD5) Previous issue date: 2013-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The loss of bone tissue is an important problem both in human and in veterinary medicines. For cranial bone defects, surgical intervention is necessary since, if not correct, these defects result in high number of cerebral lesions and neurological dysfunctions as well as esthetic sequelae. In such context, autogenous and alogenous grafts have given place to resorbable osteoconductive biomaterials. The objective of the present study was to evaluate a bone cement made from a solid phase (β-tricalcium phosphate and calcium sulfate dihydrate) and a liquid one (phosphoric acid 2M). These components were mixed in a stainless steel cube at a proportion of 1:1 and the material while still moldable, was applied in 15mm critical size defects in the cranial bone of rabbits, Scanning electron microscopy of the cement itself showed a complex surface with non-interconnected pores of 19.5±5.92 μm in diameter. Animals were separated in three experimental moments based on the time after surgical procedure (7, 28 and 90 days), comparing to defects that did not receive the material. Hematological and serum biochemistry revealed normal values during the entire experiment. Dehiscence, edema or signs of infection were not observed. In treated animals, alterations were observed on skin (hyperemia and necrosis) and brain (circular lesions of green color with vascular congestion) that evolved to healing at 90 days. These alterations may be related related to a low pH of the biomaterial during the implantation (3.38), resulted from the proportion of liquid:powder used in the present study (1:1). As suggested by computerized tomography and confirmed by histology, new bone formation occurred in control group from the margin of the defect and inside it. In treated group, bone growth was apparently less intense at 90 days when compared to the control one, limited to the margin of the defect and not observed inside it. Osteointegration was confirmed and neither signs of undesirable chronic inflammation nor the formation of a fibrous capsule around the material was observed. Thereby, the biomaterial was characterized as osteoconductor, osteointegrated, degradable in vivo and histologically biocompatible. The alterations in the color of nervous tissue and skin adjacent to the implant, although with no clinical relevance, indicate the need for a modification on the proportion of the biomaterial components. Possibly, reducing the relation liquid:powder may allow its application. / A perda de tecido ósseo é um problema grave tanto na medicina humana quanto na veterinária. No caso das falhas ósseas cranianas, a intervenção cirúrgica se faz necessária porque, se não forem corrigidas, provocam altos índices de lesões cerebrais e disfunções neurológicas, bem como graves sequelas estéticas. Nesse contexto, enxertos autógenos e alógenos têm sido substituídos por biomateriais osteocondutores e reabsorvíeis. O objetivo desse trabalho foi avaliar a utilização de um cimento ósseo formulado a partir de uma fase sólida (β-fosfato tricálcico e sulfato de cálcio di-hidratado) e uma fase líquida (ácido fosfórico 2M). Esses componentes foram misturados na proporção 1:1 e o material, ainda moldável, foi aplicado em defeitos ósseos de tamanho crítico no crânio de coelhos, com 15 mm de diâmetro. A análise do cimento pela microscopia eletrônica de varredura revelou superfície complexa com poros de 19,5 (±5,92) μm não interconectados. Os animais foram divididos em três momentos experimentais com base no tempo transcorrido após o procedimento cirúrgico (sete, 28 e 90 dias), onde os defeitos tratados foram comparados aos defeitos que não receberam o biomaterial. As análises hematológicas e da bioquímica sérica evidenciaram valores normais durante todo o experimento. Não foram observados deiscência, edema ou sinais de infecção. Nos animais tratados, foram observadas alterações na pele (hiperemia e necrose) e no cérebro (lesões circulares de coloração esverdeada com congestão vascular), que evoluíram para a cicatrização aos 90 dias. Essas alterações podem ser atribuídas ao baixo pH do biomaterial no momento de sua implantação (3,38), resultante da relação líquido/pó utilizada no presente trabalho (1:1). Foi sugerido pela tomografia computadorizada e confirmado pela análise histológica crescimento de osso novo, que no grupo controle ocorreu a partir das bordas e no interior do defeito. Já nos animais do grupo tratado esse crescimento foi menor aos 90 dias, quando comparado ao controle na mesma data, e limitou-se às bordas do defeito, não ocorrendo no interior. Foi demonstrada a osteointegração do biomaterial, não sendo observados sinais de inflamação crônica indesejável ou a formação de cápsula fibrosa ao seu redor. Após análise dos dados obtidos o biomaterial foi caracterizado como osteocondutor, osteointegrável, possuindo degradação in vivo e histologicamente biocompatível. As alterações na coloração no tecido nervoso na região do implante, mesmo sem comprometimento clínico, e as lesões de pele, indicam a necessidade de modificação da proporção dos componentes. Possivelmente, a redução da relação líquido/pó viabilizará sua aplicação.

Made available in DSpace on 2016-12-06T17:07:13Z (GMT). No. of bitstreams: 1 RESUMO.pdf: 26325 bytes, checksum: b3675c6043e597d4b7943a6b80a68275 (MD5) Previous issue date: 2001-12-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A variety of reconstructive surgical procedures rely on the strength improvement of tendon-to-tendon linkage. Thus, methods to improve tendon ruptures may allow earlier rehabilitation and fast return to the daily living. The purpose of this study was to evaluate the mechanical strength of aquilles tendon 2-mm defect in male rabbits. The created gap was filled with bovine collagen (biomaterial) in nine specimens and a suture with no filling in other nine specimens. The other aquilles tendons were the control group as pattern of normality. In all eighteen tendons (eighteen animals) the strength were tested in a material testing machine for a pull-out strength. Ultimate strength and dislocation were analyzed in all groups. One-way analysis of variance (ANOVA) at a p£ 0.05 was used to compare the biomechanical data in the sixth week period of time. There were no obvious slipping at the interface between the clamp and the muscle-tendon fixation. There was no significantly difference among the groups. For the strength variable p=0.0467 and for the displacement p=0.1950. The coefficient of variation of 30% for the control group, 25% for the biomaterial group and 18% for the suture group when analyzing the tendon strength. In the displacement data, the control group presented a coefficient of variation of 37%, biomaterial group of 25% and the 42% for the control group. The presented data have not shown any improvement using biomaterial. However, the collagen group has shown similar curves compared to the control group. / O presente estudo teve como objetivo avaliar o comportamento biomecânico do tendão calcaneano de coelhos, quando utilizado um componente biológico para o preenchimento de uma falha. Os biomateriais são substâncias biologicamente ativas, que apresentam efeito osteogênico e formador de partes moles, isto é, ativam a formação de osso e colágeno novos nos organismos vivos. Neste estudo o biomaterial foi o colágeno bovino. A amostra foi caracterizada por dezoito coelhos da raça Nova Zelândia, adultos, machos em que foi criada uma falha cirúrgica de 2 mm no tendão calcaneano de todos os animais. Em nove animais foi realizada simples sutura sem biomaterial, nos restantes nove animais foi realizada a implantação dos biomateriais nas falhas criadas. No período de seis semanas estes animais foram sacrificados e os tendões submetidos ao teste de tração. A comparação foi utilizada pelo tendão não operado, como forma de obter-se o padrão de normalidade da resistência dos tendões. Foram utilizadas as garras para o ensaio de tração, próprias da máquina de ensaios biomecânicos. Os resultados da carga máxima aplicada para a ruptura destes espécimes e o deslocamento, a partir da curva carga-deslocamento foram registrados e avaliados o comportamento biomecânico destes espécimes. Utilizando-se a análise da variância (ANOVA) com um p£ 0,05 não foram observados diferenças estatisticamente significantes entre os grupos de estudo e o grupo controle. O coeficiente de variação (CV%) em relação à variável carga máxima à falência no grupo controle foi de 30%, no grupo biomaterial 25% e no grupo sutura 18%. Na análise do grau de deslocamento, o grupo controle apresentou um CV de 37%, o biomaterial de 25% e 42% para o grupo controle. Em análise do coeficiente de variação acumulado, houve uma tendência para estabilização da curva nos grupos apresentados. Os dados acima apresentados não demonstraram um efeito benéfico na adição do colágeno bovino nestes grupos estudados. Ainda assim, em observação qualitativa, as curvas do grupo biomaterial apresentaram um traçado semelhante aos da normalidade.

Made available in DSpace on 2016-12-08T17:19:29Z (GMT). No. of bitstreams: 1 Elementos pre-textuais.pdf: 100348 bytes, checksum: eed0b75225a6274f20636cccbe0612e3 (MD5) Previous issue date: 2006-10-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In many laboratories worldwide the biocements are being studied in order to obtain new nanometric materials, with better characteristics of biocompatibility and functionality to be used in odonto-medical applications. It was observed that microporous ceramics have a better performance regarding substitution and regeneration of bone tissue, mainly the ceramics composed of calcium phosphates (Ca/P). These ceramics are being used more and more in biomedical applications because they have a mineralogical composition very similar to that of human bone apatites, and also because they have an excellent biocompatibility. The aim of this work was focused on the optimization of the powder synthesis method of bioceramics by dissolution/precipitation process and on the characterization of nanostructured calcium phosphate biocements with the molar composition of Ca/P = 1,4; 1,5; 1,6; 1,7 and 1,8. It was studied the morphology, the microstructure, physical, chemical, mechanical properties, thermal behavior and the hydration. The bioceramic powders obtained from the rotating evaporator were treated at 1300°C for 2 hours, providing the biocement. A preliminary study of hydration was performed between 5 and 25 minutes; after it was performed the hydration of cylindrical samples for a period of 1, 2, 3, 7 and 28 days. Also, it was carried out a parallel study, sintering samples with cylindrical and square shapes. Afterward, it was carried out the characterization studies. The results let certainly that the synthesis method permitted obtains of slim bioceramics powders of nostructured calcium phosphate. The thermal treatment at 1300°C/2 hours provided the biocements, compound by b-calcium phosphate and hydroxyapatite. The hydration study of 1 until 28 days , showed the modifications of phase and a microporous microstructure formed by crystalline fibers, it occurred by hydration process. It observed that the shape and size of crystalline fibers, influenced directly about the mechanical properties of the hydrated samples. And finally, it was presented a conclusion of this work and some considerations to be taken in account in the following works. / Os biocimentos vêm sendo estudados por vários centros de pesquisa com a finalidade de obter novos materiais nanométricos com características de biocompatibilidade, biofuncionalidade para serem utilizados em aplicações médicas e odontológicas. Constatou-se que as cerâmicas microporosas destacam-se em aplicações de substituição e regeneração de tecidos ósseos, principalmente as cerâmicas formadas pela composição Ca/P, os fosfatos de cálcio. Estas cerâmicas vêm tomando um espaço importante em aplicações biomédicas em razão de suas características mineralógicas semelhantes às apatitas da estrutura óssea do esqueleto humano e também por apresentarem boa biocompatibilidade. O objetivo deste trabalho concentrou-se na otimização do método de síntese dos pós biocerâmicos pelo processo via úmida e caracterização de biocimentos nanoestruturados de fosfato de cálcio nas composições Ca/P = 1,4; 1,5; 1,6; 1,7 e 1,8 molar. Os estudos de caracterização foram realizados em nível morfológico, microestrutural, físico, químico, das propriedades mecânicas, do comportamento térmico e de hidratação. O pó biocerâmico recuperado do evaporador foi tratado à temperatura de 1300°C/2h, fornecendo o biocimento. Um estudo preliminar de hidratação foi realizado em tempos de 5 a 25 minutos; posteriormente realizou-se a hidratação sob corpos de prova cilíndricos com tempos de 1, 2, 3, 7 e 28 dias. Realizou-se também um estudo paralelo, sintetizando corpos de prova na forma cilíndrica e barretes. Posteriormente, foram realizados os estudos de caracterização. Os resultados deixaram claro, que o método de síntese via úmida permitiu a obtenção de finos pós biocerâmicos de fosfato de cálcio nanoestruturados. O tratamento térmico a 1300ºC/2h forneceu os biocimentos, compostos por fosfato de cálcio-b e hidroxiapatita. O estudo de hidratação de 1 a 28 dias, colocou em evidência as modificações de fase e de uma microestrutura microporosa formada por fibras cristalinas, ocorridas pelo processo de hidratação. Observou-se que a forma e tamanho das fibras cristalinas, influenciaram diretamente sobre as propriedades mecânicas dos corpos de prova hidratados. Por fim serão apresentadas uma conclusão geral e algumas considerações a serem levadas em conta para trabalhos futuros.

Made available in DSpace on 2014-12-17T14:03:39Z (GMT). No. of bitstreams: 1 JanaDFQ_DISSERT.pdf: 1850683 bytes, checksum: e5171a51c7f0d0df9cc94a873195a0f7 (MD5) Previous issue date: 2011-11-29 / Commercially pure Titanium (cp Ti) is a material largely used in orthopedic and dental implants due to its biocompatibility properties. Changes in the surface of cp Ti can determine the functional response of the cells such as facilitating implant fixation and stabilization, and increased roughness of the surface has been shown to improve adhesion and cellular proliferation. Various surface modification methods have been developed to increase roughness, such as mechanical, chemical, electrochemical and plasma treatment. An argon plasma treatment generates a surface that has good mechanical proprieties without chemical composition modification. Besides the topography, biological responses to the implant contribute significantly to its success. Oxidative stress induced by the biomaterials is considered one of the major causes of implant failure. For this reason the oxidative potential of titanium surfaces subjected to plasma treatment was evaluated on this work. CHO-k1 cells were cultivated on smooth or roughed Ti disks, and after three days, the redox balance was investigated measuring reactive oxygen species (ROS) generation, total antioxidant capacity and biomarkers of ROS attack. The results showed cells grown on titanium surfaces are subjected to intracellular oxidative stress due to hydrogen peroxide generation. Titanium discs subjected to the plasma treatment induced less oxidative stress than the untreated ones, which resulted in improved cellular ability. Our data suggest that plasma treated titanium may be a more biocompatible biomaterial. / O Tit?nio comercialmente puro (cpTi) ? amplamente utilizado em implantes ortop?dicos e dentais gra?as ?s suas propriedades f?sico-qu?micas. Mudan?as na superf?cie do cpTi podem determinar respostas funcionais nas c?lulas influenciando a fixa??o e estabiliza??o do implante. Muitos m?todos de modifica??o na superf?cie podem ser aplicados para aumentar a rugosidade como, por exemplo, tratamentos mec?nicos, qu?micos, eletroqu?micos e a plasma. Este ?ltimo, quando realizado em atmosfera de arg?nio gera uma superf?cie rugosa com boas propriedades mec?nicas sem alterar a composi??o qu?mica do material. Superf?cies rugosas geralmente s?o mais biocompat?veis que as lisas, pois esse tipo de topografia facilita os processos de ades?o e prolifera??o celular. Al?m da topografia, as rea??es biol?gicas desencadeadas em resposta ao implante contribuem de forma significativa para o sucesso do mesmo. Dentre estas rea??es, o estresse oxidativo tem sido apontado como um dos principais respons?veis por falhas na implanta??o. Diante do exposto, o potencial oxidativo das superf?cies de tit?nio tratadas e n?o tratadas a plasma em atmosfera de arg?nio foi avaliado neste trabalho. Para tanto, c?lulas CHOk1 foram cultivadas sobre as superf?cies de tit?nio (tratadas e n?o tratadas). Ap?s tr?s dias de cultivo o potencial oxidativo foi investigado por meio da quantifica??o de esp?cies reativas, an?lise da capacidade antioxidante e an?lise de biomarcadores de dano oxidativo (lipoperoxida??o, carbonila??o prot?ica e oxida??o das bases do DNA). Os resultados obtidos indicam que ambas as superf?cies de tit?nio induzem estresse oxidativo, sendo o per?xido de hidrog?nio a principal esp?cie envolvida. O tratamento a plasma reduziu os danos oxidativos e promoveu melhora na habilidade celular em responder ao estresse oxidativo. Deste modo, a modifica??o da superf?cie de tit?nio atrav?s do tratamento a plasma pode ser uma alternativa para a obten??o de um material com melhor biocompatibilidade. / 2020-01-01

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / As biocerÃmicas sÃo substÃncias ou combinaÃÃo de substÃncias que tem aplicabilidade clÃnica, com a finalidade de restituir ou tratar ÃrgÃos, tecidos ou funÃÃes do corpo humano. SÃo quimicamente muito estÃveis e, portanto, pouco provÃveis de induzir uma resposta biolÃgica adversa. As biocerÃmicas mais empregadas na reconstituiÃÃo de tecidos sÃo à base de fosfato de cÃlcio, com razÃo Ca/P que varia de 0,5 a 2,0; formando diferentes fases, dentre as quais a mais estudada à a hidroxiapatita, cuja composiÃÃo quÃmica à semelhante à fase inorgÃnica dos ossos e dentes. A hidroxiapatita pode ser obtida atravÃs de diferentes mecanismos em fase sÃlida ou via Ãmida. Neste estudo, foram obtidas biocerÃmicas de apatitas por meio de uma reaÃÃo em estado sÃlido via radiaÃÃo por microondas, utilizando os reagentes: hidrÃxido de cÃlcio [Ca(OH)2] e difosfato de cÃlcio (CaHPO4). Os pÃs obtidos foram submetidos a tratamentos tÃrmicos de 850ÂC e 1050ÂC e caracterizados por DifraÃÃo de Raios-x (DRX), Espectroscopia de Transformada de Fourier por Raios Infravermelhos (FTIR), FluorescÃncia de Raios-X (FRX), AnÃlise TermogravimÃtrica (ATG) e Microscopia EletrÃnica de Varredura (MEV). As fases predominantes foram identificadas como sendo hidroxiapatita e β-fosfato tricÃlcio. Em seguida, os pÃs foram prensados unixialmente em molde cilÃndrico, com ligante, e sinterizados a 1200ÂC por 1 hora. A microestrutura final apresentou a fase cristalina hidroxiapatita (HA) / Bioceramic are substances or combination of substances which has some clinical applicability and can be used for treating or replacing any tissue, organ or function of the body. They are chemically stable and have almost no adverse biological effects. The most widely used bioceramics for tissue reconstitution are calcium phosphate based bioceramics having Ca/P ratio changing from 0.5 to 2.0, which leads to diferent phases. The most important phase is hydroxyapatite due to its chemical composition, which is similar to that of hard tissues. Hydroxyapatite can be obtained by different mechanisms such as wet methods and solid-state reactions. In this study, apatite bioceramics were obtained from solid-state reaction by Microwave Irradiation, using calcium phosphate (CaHPO4) and calcium hydroxide [Ca(OH)2]. The powders obtained were heat treated at 850ÂC and 1050ÂC and characterized by X-Ray Diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM). The predominant phases identified were hydroxyapatite and β-tricalcium phosphate. The powders were uniaxially pressed in cylindrical dyes and sintered at 1200ÂC for 1hour. Final microstructure presented the hydroxyapatite (HA) phase

Conselho Nacional de Desenvolvimento Científico e Tecnológico / In arthopedic surgery thera are.frequentlysituations in that the surgeon faces severa bone losses caused by high-energy trauma, tumors of infections. Repairing these losses require knowledge about fillingmateriais. Those materiais can be biological, synthetic or metallic, with emphasis in bony grafts and biomaterial implants. The increase of the use of birds as pets is leading to an increasing number of clinicaland surgical cases related to this taxon, where fractures are the most commonly observed surgical problems. The objective of this study was to evaluate clinical, radiological,macroscopic and microscopic effects of the polyurethane derived from castor oU(Ricinus communis) polymer,when implanted in the humerus of domestic quails (Cotumixjaponica).There were used twenty male and female quails, randomly distributedin four groups of tive individuais.The birds received the implantsin the left hurnerus, being submitted to daily physical examination during the postoperative period, immediate and biweekll radíological examination, and maaoscopic and microscopicevaluation at the 15 ,30th, 60thand 90thdays. Clinically,there were not observed local, regional or systemic changas. Radiologically, it was observed increase in local density with no signs of changes in bone or adjacent tissue, as well as in the air sacs. Macroscopicanalysis revealed that the polyurethane derived trom castor oi!polymerwas not absorbed in none of the four groups, remaining implanted within the pneumatic bone. Its resistance, however, have changed. Microscopic examination evidenced minimum inflammatoryreadion, slight fibrosis around the implants, and osteo-integration with presence of trabeculi and bone marrow inside the implants. Concluding, implants of polyurethane derived trom castor oil polymer are biocompatiblein quails, with occurrence of osteo-integration, and can be used in orthopedic surgery in this species. / Na cirurgia ortopédica são freqüentes as situações em que o cirurgião se depara com grandes perdas ósseas, provocadas especialmente por traumatismos de alta energia. A reparação de tais perdas requer grande conhecimento a respeito de materiais que possam ser utilizados para seu preenchimento. Esses materiais podem ser biológicos.sintéticos ou metálicos, destacando-se os enxertos ósseos e os implantes de biomateriais.O incremento no emprego de aves como animais de estimação tem levado ao aumento na casu(stica clínica e cirúrgica relacionada a esse grupo taxonOmico.Dentre os problemas cirúrgicos observados em aves, as fraturas têm maior destaque. O objetivo deste estudo foi avaliar os efeitos: d(nico, radiológico,macroscópico e histológicodo poHmerode mamona (Ricinus communis) implantado no úmero de codornas domésticas (Cotumixjaponica). Para isso, foram empregadas 20 codornas, machos e fêmeas, separadas aleatoriamente em quatro grupos de cinco indivlduos. As aves receberam o implante no úmero esquerdo, passando por exame flsico diário durante o perlodo pós-operatório, avaliação radiológicaimediata e quinzenal, e avaliação macroscópica e histológicaaos 15, 30, 60 e 90 dias. Clinicamente, não foram observadas alterações locais, regionais ou sistêmicas. Ao exame radiológico,notou-se aumento da densidade local, sem sinais de alteração óssea ou dos tecidos adjacentes, bem como das sacos aéreos. A análise macrosc6pica revelou que a poliuretana derivada do poUmerode mamona não foi absorvida em nenhum dos quatro grupos, permanecendo implantada no interior do osso pneumático, notando-se, porém, alteração em sua resistência. O exame histopatológico evidenciou mlnima reação inflamatória,discreta fibrose ao redor do implante e osseointegração, pela presença de trabéculas e medula óssea no interior do implante. Conduiu-se que a poliuretana derivada do poUmero de mamona é biocompatlvel em codornas, com ocorrência de osseointegração, podendo, portanto ser utilizadaem cirurgiaortopédica.

Aus der Sicht von Klinikern – Orthopäden und Unfallchirurgen – besteht ein großer Bedarf an degra¬dierbaren Knochenersatzmaterialien für den osteoporotischen und den krebskranken Knochen. Fraktu¬ren am Oberschenkelhals oder auch der Wirbelsäule heilen bei diesen systemischen Erkrankungen gar nicht oder nur sehr langsam. Frakturen des gesunden Knochens heilen ins¬besondere bei älteren Patienten schwer, wenn große Defektbereiche vorhanden sind. Gilt bei einem ge¬sunden Patienten ein Defekt von etwa 1,5 – 2 cm als überkritisch und bedarf somit der Versorgung mit einem Knochen¬ersatz¬material, so kann bei einem älteren oder erkrankten Menschen bereits eine Spalt¬breite von mehr als 3 mm problematisch sein. Der Sonderforschungsbereich Transregio 79 mit dem Thema 'Werkstoffe für die Geweberegeneration im systemisch erkrankten Knochen' hat sich dieses Problems angenommen und will es ätiologiebasiert durch die Verbindung von Erkenntnissen und Charakterisierungs-methoden aus Werkstoffwissenschaft, Biologie und Medizin lösen. Die vorliegende Dissertation wurde im Rahmen dieses Vorhabens und in der Gruppe Biomimetische Materialien und Biomaterialanalytik des Instituts für Werkstoffwissenschaft, Professur Biomaterialien, der Technischen Universität Dresden erarbeitet. Sie beschäftigt sich vorrangig mit der Entwicklung von Knochenersatz¬material für den gesunden sowie den osteoporotischen Knochen. Der Arbeitshypothese folgend, dass die Defekt-/Frakturheilung im osteoporotischen Knochen durch Knochenersatzmaterial bestehend aus Calcium-/Strontiumphosphaten verbessert werden kann, soll die Ionenfreisetzung durch geeignete Kristallstrukturen gezielt eingestellt werden, um den Knochenwiederaufbau direkt über die Osteo¬blastenaktivität oder indirekt über die Cytokinausschüttung der Osteoklasten zu stimulieren. Für die Materialentwicklung sind eine hinreichende Kenntnisse über die Struktur und den Aufbau des Knochens, über die Mineralisation und die Zellbiologie des Knochens einschließlich des Immunsystems notwendig. Zu Beginn der Arbeit war es deshalb notwendig, diesen Kenntnisstand zur Mineralbildung im Knochen zu vertiefen. Eine intensive Zusammenarbeit mit Projekten innerhalb des Transregio 79, die sich der Strukturaufklärung und der Zellbiologie des Knochens widmen beziehungsweise die Tierexperimente durchführen, war daher erforderlich. Diese Verknüpfung erfordert eine tiefgehende Auseinandersetzung mit der Frakturheilung, um interdisziplinär erfolgreich wirken zu können. Im Verlauf der Materialentwicklung erwies es sich als vorteilhaft, auch im eigenen Labor Zellkultur¬untersuchungen durchzuführen. Sie ermöglichten eine schnellere Umsetzung von Erkenntnissen der Zell¬reaktion in die Materialkonzeption. Aus werkstoffwissenschaftlicher Sicht ist der Knochen ein durch die Evolution geprägtes und hinsicht¬lich seiner mechanischen und biologischen Eigenschaften herausragend aufgebautes Verbundmaterial, das aus organischen und anorganisch nichtmetallischen Komponenten besteht und hierarchisch strukturiert ist. Kollagen I und Hydroxylapatit sind seine Hauptbestandteile. Daneben gibt es aber eine Reihe von Calciumphosphatstrukturen und Spuren von Fremdionen sowie nichtkollagenen Proteinen, deren Wirkung im Zuge der Mineralisation bisher kaum verstanden wird. Die zeitliche Abfolge, die Vielzahl an beteiligten Komponenten und die zelluläre Steuerung ergeben eine umfangreiche Parametervielfalt, die sich zum Teil durch Kompensationsmechanismen einer definitiven Ursachen-Wirkungs-Beschreibung entziehen. Eine Auseinandersetzung mit dem Knochenaufbau ist jedoch essen¬tiell für die Orientierung am natürlichen Vorbild. Zudem bedarf es der Kenntnis des zellulären Verhal¬tens auf extrazelluläre Einflüsse, um die Biomaterialcharakterisierung und eine geeignete Material¬modifizierung zu vollziehen. Deshalb wird im Stand des Wissens im nachfolgenden Kapitel zunächst auf die Struktur und den Aufbau des Knochens eingegangen, ehe auf die Besonderheiten der Mineralisation Bezug genommen wird. Letztere erfolgt nicht nach dem Prinzip der klassischen Mineralisation. Stattdessen liegen im Knochen Nanokristallite vor, die mithilfe organischer Moleküle zu sogenannten mesoskopischen Partikeln zusammengeführt werden. Die Kristallisation wird auf diesem Weg unabhängiger von Ionenprodukten und kann ohne Änderungen von pH-Werten stattfinden. Eine Schlüs¬sel¬position bei dieser Mineralisation nehmen strukturdirigierende Moleküle ein. Es ist bisher unklar geblieben, welche strukturdirigierenden Moleküle in welcher Reihenfolge oder auch gemeinsam im Knochen wirken und welches Molekül den Mineralisationsprozess einleitet und wie es mit den Haupt-komponenten des Knochens in Wechselwirkung steht. Das Materialkonzept sah daher von Beginn an vor, knochennahe Komponenten wie Kollagen Typ I und Calciumphosphatphasen als Grund¬bestandteile für den Knochenersatz zu verwenden, aber auch das nicht¬kollagene Protein Osteocalcin beziehungs¬weise Asparaginsäure als dessen Modellsubstanz werden als mögliche strukturdirigierende Moleküle mit einbezogen. Aufbauend auf dem gegenwärtigen Stand des Wissens wurde auch Strontium als Fremdion, wegen seiner bekannten positiven Wirkung auf den osteoporotischen Knochen, mit in das Konzept eingebunden. Weil bei einer Einführung in die medizinische Praxis auch ökonomische Gesichtspunkte eine wichtige Rolle spielen, war es naheliegend, statt Tropokollagen und Kollagen¬fibrillen auch Gela¬tine als organische Hauptkomponente zu verwenden. Die Forschung an einem temporären Knochenersatz für die Behandlung überkritischer Defekte und Frakturen durch ein degradierbares Biomaterial erfordert die Anregung der Knochenneubildung und gegebenenfalls die Einbindung in den Remodellierungsprozess, was einerseits von der biologisch medizinischen Seite, andererseits aber von der Seite der Handhabbarkeit im operativen Einsatz zu beur¬teilen ist. Beiderseits sind werkstoffwissenschaftliche Untersuchungen und Beschreibungen der Struktur sowie des Gefüges und die Herstellung einer Beziehung zu den daraus resultierenden Eigenschaften erforderlich. Auf dieser Basis wird aus der Materialforschung der technisch anwendbare Werkstoff. Im Anschluss an den Stand des Wissens werden die Ergebnisse zur Knochenuntersuchung, ebenso wie die der verschiedenen Mineralisationsmethoden aufgeführt und jeweils in den darauffolgenden Kapiteln diskutiert, um die Weiterentwicklung der Biomaterialsynthese zu erläutern. Das daraus resultierende Materialkonzept wird ausführlich in vitro charakterisiert und die Materialauswahl für den ersten in vivo Einsatz im Rahmen des Transregio 79 im osteoporotischen Rattenmodell erörtert. Die abschließende Zusammenfassung führt die Teilerkenntnisse zusammen und ermöglicht einen Ausblick für die weitere Materialentwicklung auf der Basis biomimetisch mineralisierter organischer Makromoleküle.:Danksagung Eigenständigkeitserklärung Inhaltsverzeichnis Abkürzungsverzeichnis 1 Einleitung 2 Stand des Wissens 2.1 Biomineralisation und Selbstorganisation: Der Knochen 2.1.1 Organische Knochenbestandteile: Kollagen und Osteocalcin 2.1.2 Anorganik des Knochens 2.1.3 Hierarchischer Aufbau des Knochens 2.1.4 Knochenzellen und die Knochenremodellierung 2.1.5 Physiologische Bedeutung von Calcium und Strontium 2.2 Materialien und Werkstoffe für den Knochenersatz 2.2.1 Synthetische Calciumphosphate 2.2.2 In vitro Mineralisation von organischen Makromolekülen 2.2.3 Bioaktivität von Knochenersatzmaterialien 2.2.4 Natürliche Knochenersatzmaterialien 2.2.5 Artifizielle Knochenersatzmaterialien 2.3 Zusammenfassung 3 Materialien und Methoden 3.1 Dual-Membran-Migrationsmethode und Doppelmigrationsmethode 3.1.1 Kollagenaufreinigung 3.1.2 Resuspendierung und Fibrillogenese des Tropokollagens 3.1.3 Dual-Membran-Migrationsmethode 3.1.4 Doppelmigrationsmethode 3.2 Fällungsreaktion im Batch-Prozess 3.2.1 Mineralpräzipitation – Mineralisation und Reifung 3.2.2 Mineralverarbeitung zur Probekörperherstellung 3.3 Charakterisierung und Analysemethoden 3.3.1 Strukturanalytik 3.3.2 Morphologische Untersuchungen 3.3.3 Mechanische Charakterisierung 3.3.4 Glühverlust 3.3.5 Optische Emissionsspektroskopie mit induktiv gekoppeltem Plasma (ICP OES) 3.3.6 Dichte und Porosität 3.3.7 Degradation in physiologische Lösungen: Bioaktivität, pH Wertmessung und Masseänderung 3.3.8 Kultivierung von humanen mesenchymalen Stammzellen und humanen Monozyten 3.3.9 Biochemische Untersuchungsmethoden 3.4 Statistische Auswertung 4 Ergebnisse und Diskussion 4.1 Analytik humanen Knochens 4.1.1 Transmissionselektronenmikroskopische Analyse 4.1.2 Hypothese der Kollagenmineralisation 4.2 Dual-Membran-Migrationsmethode: (Tropo-)Kollagen mit poly Asparaginsäure und Osteocalcin 4.2.1 Mineralisation von Kollagenscaffolds, suspendiertem fibrillärem Kollagen und Tropokollagen 4.2.2 Erkenntnisse aus der in vitro Mineralisation mittels DM3 4.3 Zusammenfassung zur Hypothese der in vivo Kollagenmineralisation mit in vitro Vergleich 4.4 Doppelmigrationsmethode: Mineralisation von Gelatine 4.4.1 Struktur der gebildeten Calciumphosphatphasen 4.4.2 Degradation der mineralisierten Gelatine 4.4.3 Untersuchung des Zellverhaltens in der Osteoblasten/Osteoklasten-Co-Kultivierung 4.4.4 Diskussion des ormoHAp-Aufbaus und der Einflussnahme auf die hMSC/Monozyten-Co-Kultur 4.5 Fällungsmethode: Mineralisierung von phosphatvorstrukturierter Gelatine durch Calciumphosphate 4.5.1 Kristallstruktur und Materialcharakterisierung 4.5.2 Analyse der mechanischen Eigenschaften, des Degradationsverhaltens und der Bioaktivität 4.5.3 In vitro Biokompatibilität von verpresstem gelatinemodifizierten Calciumphosphat 4.5.4 Zusammenfassung der Analytik des gelatinemodifizierten Calciumphosphats 4.6 Fällungsmethode: Mineralisierung von phosphatvorstrukturierter Gelatine in Gegenwart von Calcium- und Strontiumionen 4.6.1 Charakterisierung der gelatinemodifizierten Calcium-/Strontiumphosphate 4.6.2 Probekörperherstellung 4.6.3 Eigenschaften des Biomaterials: Degradation und in vitro Biokompatibilität 4.6.4 Untersuchung der in vitro Biokompatibilität von gelatinemodifizierten Calcium-/Strontiumphosphaten 4.6.5 Erste Resultate der in vivo Implantation im Femurdefekt osteoporotischer Ratten 5 Zusammenfassung 6 Ausblick Abbildungsverzeichnis Tabellenverzeichnis Quellenverzeichnis Anhang A1 Aufbereitungs- und Testchemikalien A2 Zellkulturmaterialien A3 Puffer und Lösungen A4 Technische Geräte, Hilfsmittel und Verbrauchsmaterialien Eigene Publikationen und Mitautorschaften / From the point of view of clinicians - orthopedists and trauma surgeons - there is a great need for degradable bone substitutes for osteoporotic and cancerous bone. Fractures of the femoral neck or even the spine do not heal at all or only very slowly in these systemic diseases. Fractures of healthy bone heal with difficulty, especially in older patients, if large defect areas are present. While a defect of about 1.5 - 2 cm in a healthy patient is considered supercritical and thus requires the use of bone substitute material, a gap width of more than 3 mm in an elderly or affected person can be problematic. The Collaborative Research Center Transregio 79 with the topic 'Materials for Tissue Regeneration within Systemically Altered Bone' has taken up this problem and aims to solve it in an etiology-based manner by combining findings and characterization methods from materials science, biology and medicine. This dissertation was written within the framework of this project and in the Biomimetic Materials and Biomaterial Analysis Group of the Institute of Materials Science, Chair of Biomaterials, at the Technical University of Dresden. It is primarily concerned with the development of bone substitute materials for healthy and osteoporotic bone. Following the working hypothesis that defect/fracture healing in osteoporotic bone can be improved by bone substitute material consisting of calcium/strontium phosphates, the ion release is to be specifically adjusted by suitable crystal structures in order to stimulate bone reconstruction directly via osteoblast activity or indirectly via cytokine release by osteoclasts. Sufficient knowledge of the structure and composition of bone, of mineralization and of the cell biology of bone, including the immune system, is necessary for material development. At the beginning of the work, it was therefore necessary to deepen this knowledge of mineral formation in bone. An intensive cooperation with projects within the Transregio 79, which are dedicated to the structural elucidation and the cell biology of bone or which perform animal experiments, was therefore necessary. This linkage requires an in-depth examination of fracture healing in order to be able to work successfully on an interdisciplinary basis. In the course of material development, it proved advantageous to also carry out cell culture investigations in our own laboratory. They enabled faster implementation of cell reaction findings in the material concept. From the point of view of materials science, bone is an evolutionary composite material with outstanding mechanical and biological properties, consisting of organic and inorganic non-metallic components with a hierarchical structure. Collagen I and hydroxyapatite are its main components. In addition, however, there are a number of calcium phosphate structures and traces of foreign ions as well as non-collagenous proteins, whose action in the course of mineralization is poorly understood so far. The temporal sequence, the multitude of components involved and the cellular control result in an extensive variety of parameters, some of which elude a definitive cause-effect description by compensatory mechanisms. However, a discussion of bone structure is essential for orientation to the natural model. In addition, knowledge of the cellular response to extracellular influences is required for biomaterial characterization and suitable material modification. The researched material concept is characterized in detail in vitro and the material selection for the first in vivo application within the Transregio 79 in the osteoporotic rat model is discussed. The final summary brings together the partial findings and provides an outlook for further material development based on biomimetically mineralized organic macromolecules.:Danksagung Eigenständigkeitserklärung Inhaltsverzeichnis Abkürzungsverzeichnis 1 Einleitung 2 Stand des Wissens 2.1 Biomineralisation und Selbstorganisation: Der Knochen 2.1.1 Organische Knochenbestandteile: Kollagen und Osteocalcin 2.1.2 Anorganik des Knochens 2.1.3 Hierarchischer Aufbau des Knochens 2.1.4 Knochenzellen und die Knochenremodellierung 2.1.5 Physiologische Bedeutung von Calcium und Strontium 2.2 Materialien und Werkstoffe für den Knochenersatz 2.2.1 Synthetische Calciumphosphate 2.2.2 In vitro Mineralisation von organischen Makromolekülen 2.2.3 Bioaktivität von Knochenersatzmaterialien 2.2.4 Natürliche Knochenersatzmaterialien 2.2.5 Artifizielle Knochenersatzmaterialien 2.3 Zusammenfassung 3 Materialien und Methoden 3.1 Dual-Membran-Migrationsmethode und Doppelmigrationsmethode 3.1.1 Kollagenaufreinigung 3.1.2 Resuspendierung und Fibrillogenese des Tropokollagens 3.1.3 Dual-Membran-Migrationsmethode 3.1.4 Doppelmigrationsmethode 3.2 Fällungsreaktion im Batch-Prozess 3.2.1 Mineralpräzipitation – Mineralisation und Reifung 3.2.2 Mineralverarbeitung zur Probekörperherstellung 3.3 Charakterisierung und Analysemethoden 3.3.1 Strukturanalytik 3.3.2 Morphologische Untersuchungen 3.3.3 Mechanische Charakterisierung 3.3.4 Glühverlust 3.3.5 Optische Emissionsspektroskopie mit induktiv gekoppeltem Plasma (ICP OES) 3.3.6 Dichte und Porosität 3.3.7 Degradation in physiologische Lösungen: Bioaktivität, pH Wertmessung und Masseänderung 3.3.8 Kultivierung von humanen mesenchymalen Stammzellen und humanen Monozyten 3.3.9 Biochemische Untersuchungsmethoden 3.4 Statistische Auswertung 4 Ergebnisse und Diskussion 4.1 Analytik humanen Knochens 4.1.1 Transmissionselektronenmikroskopische Analyse 4.1.2 Hypothese der Kollagenmineralisation 4.2 Dual-Membran-Migrationsmethode: (Tropo-)Kollagen mit poly Asparaginsäure und Osteocalcin 4.2.1 Mineralisation von Kollagenscaffolds, suspendiertem fibrillärem Kollagen und Tropokollagen 4.2.2 Erkenntnisse aus der in vitro Mineralisation mittels DM3 4.3 Zusammenfassung zur Hypothese der in vivo Kollagenmineralisation mit in vitro Vergleich 4.4 Doppelmigrationsmethode: Mineralisation von Gelatine 4.4.1 Struktur der gebildeten Calciumphosphatphasen 4.4.2 Degradation der mineralisierten Gelatine 4.4.3 Untersuchung des Zellverhaltens in der Osteoblasten/Osteoklasten-Co-Kultivierung 4.4.4 Diskussion des ormoHAp-Aufbaus und der Einflussnahme auf die hMSC/Monozyten-Co-Kultur 4.5 Fällungsmethode: Mineralisierung von phosphatvorstrukturierter Gelatine durch Calciumphosphate 4.5.1 Kristallstruktur und Materialcharakterisierung 4.5.2 Analyse der mechanischen Eigenschaften, des Degradationsverhaltens und der Bioaktivität 4.5.3 In vitro Biokompatibilität von verpresstem gelatinemodifizierten Calciumphosphat 4.5.4 Zusammenfassung der Analytik des gelatinemodifizierten Calciumphosphats 4.6 Fällungsmethode: Mineralisierung von phosphatvorstrukturierter Gelatine in Gegenwart von Calcium- und Strontiumionen 4.6.1 Charakterisierung der gelatinemodifizierten Calcium-/Strontiumphosphate 4.6.2 Probekörperherstellung 4.6.3 Eigenschaften des Biomaterials: Degradation und in vitro Biokompatibilität 4.6.4 Untersuchung der in vitro Biokompatibilität von gelatinemodifizierten Calcium-/Strontiumphosphaten 4.6.5 Erste Resultate der in vivo Implantation im Femurdefekt osteoporotischer Ratten 5 Zusammenfassung 6 Ausblick Abbildungsverzeichnis Tabellenverzeichnis Quellenverzeichnis Anhang A1 Aufbereitungs- und Testchemikalien A2 Zellkulturmaterialien A3 Puffer und Lösungen A4 Technische Geräte, Hilfsmittel und Verbrauchsmaterialien Eigene Publikationen und Mitautorschaften

In this study, structure-property relationships in the ironclad beetle (Zopherus nodulosus haldemani) exoskeleton are quantified to develop novel bio-inspired impact resistance technologies. The hierarchical structure of this exoskeleton was observed at various length scales for both the ironclad beetle pronotum and elytron. The exocuticle and endocuticle layers provide the bulk of the structural integrity and consist of chitiniber planes arranged in a Bouligand structure. The pronotum consists of a layered structure, while elytron consists of an extra layer with “tunnel-like” voids running along the anteroposterior axis along with smaller interconnecting “tunnel-like” voids in the lateral plane. Energy dispersive X-ray diffraction revealed the existence of minerals such as calcium carbonate, iron oxide, zinc oxide, and manganese oxide. We assert that the strength of this exoskeleton could be attributed to its overall thickness, the epicuticle layer thickness, the existence of various minerals embedded in the exoskeleton, and its structural hierarchy. The thickness of the exoskeleton correlates to a higher number of chitiniber planes to increase fracture toughness, while the increased thickness of the epicuticle prevents hydration of the chitiniber planes. In previous studies, the existence of minerals in the exoskeleton has been shown to create a tougher material compared to non-mineralized exoskeletons.

The in vitro production of ceramic implants used for cranial defect repair can be challenging and complex. In this thesis, a raw material in such a production has been mapped in order to optimize the production process. The current production leaves variations in the handling properties of the calcium phosphate cement (CPC), such as the viscosity and setting performance. The problems originate from the in-house recrystallization of the raw material monocalcium phosphate monohydrate (MCPM) with a 70% ethanol solution. The treatment of MCPM is strongly dependent on the relative humidity and the current process is not reliable and leaves unwanted fluctuations in the quality of MCPM. Various material and process parameters were investigated to get a deeper knowledge of MCPM in the specific process. The mapping resulted in new information about how the MCPM recrystallizes and how it depends on the evaporation of the ethanol solution during the treatment. Other findings were that the particle size distribution of MCPM is not the only factor controlling the viscosity of the CPC; the density and shape of the MCPM particles may also influence the handling properties. The mapping led to a process optimization suggestion where the amount of ethanol solution is adjusted to the relative humidity during the recrystallization to neutralize the effect of the humidity. The adjustment of ethanol solution volume means the evaporation can be controlled and in theory, constant quality of MCPM can be maintained. Unfortunately, the new method needs additional data to be fully effective but shows great potential.

O tratamento da erosão dental transformou-se no novo desafio do século XXI e a restauração direta com resina composta é uma das opções de tratamento para lesões severas, em que há comprometimento estético e funcional. Dentro desse contexto, novos materiais restauradores têm sido avaliados, como materiais contendo flúor em sua composição. Desta forma, o presente estudo teve como por objetivo avaliar in vitro a resistência de união da resina composta contendo ou não biomaterial S-PRG (Ionômero de Vidro com Superfície Pré-Ativada) à dentina erodida. A dentina oclusal planificada de 30 molares humanos (n=15) teve metade de sua face protegida com verniz ácido resistente (dentina hígida - grupo controle), enquanto na outra metade foi produzida uma lesão de erosão através da ciclagem em ácido cítrico 0,05 M (pH 2,3, 10 minutos, 6x/dia) e solução supersaturada (pH 7,0, 60 minutos entre os ataques ácidos). Em cada substrato, foram testados dois sistemas adesivos (um autocondicionante e outro com condicionamento prévio) e duas resinas compostas - uma com nanopartículas (Z350-3M/ESPE) e uma que contém biomaterial S-PRG(Ionômero de Vidro com Superfície Pré-Ativada) em sua composição (Beautifil II -Shofu Inc.). Foram, então, confeccionados cilindros de resina composta, os quais foram submetidos à avaliação da Resistência de União através do ensaio de microtração, após armazenamento em água por 24 horas. A análise do padrão de fratura foi realizada em microscópio ótico (40x). Os valores obtidos de resistência de união (MPa) foram submetidos aos testes de ANOVA (dois fatores) e de comparações múltiplas de Tukey (p<0,05). De acordo com os resultados, não houve diferença estatisticamente significativa entre a interação substrato e materiais restauradores (p=0.711). No entanto, houve diferença entre os substratos (p<0,001) e os materiais restauradores (p=0,002) avaliados. Quanto à resistência de união, os valores obtidos foram: G1 (47,5 ± 12,2 MPa), G2 (34,1 ± 15,8 MPa), G3(31,0 ± 8,3 MPa) e G4 (15,5 ± 13,6 MPa). Os resultados, revelaram uma diferença estatisticamente significante nos substratos avaliados e materiais restauradores. Dentro dos limites do presente estudo, conclui-se que a resistência de união no substrato erodido é inferior ao substrato hígido e que o sistema adesivo autocondicionante contendo biomaterial S-PRG(Ionômero de Vidro com Superfície Pré-Ativada) resulta em menor resistência de união da resina composta à dentina hígida ou erodida. / The treatment of dental erosion has become the new challenge of the 21st century and direct restoration with composite resin is one of the treatment options for severe injuries, in which there is aesthetic and functional impairment. Within this context, new restorative materials have been introduced containing fluoride in their composition. In this way, the objective of the present in vitro study was to evaluate the bond strength of composite resin containing or not biomaterial (S-PRG- Surface Pre-Reacted Glass ) to the eroded dentine. Planned occlusal dentin of 30 human molars (n = 15) had half of its surface protected with acid resistant varnish (sound dentin - control group), while on the other half an erosion lesion was produced by cycling in 0.05 citric acid M (pH 2.3, 10 minutes, 6x/day) and supersaturated solution (pH 7.0, 60 minutes between acid attacks). On both eroded and non-eroded substrates, two adhesive systems (one self-etching and one with pre-conditioning) and two composite resins (one with nanoparticles (Z350-3M / ESPE) and one containing biomaterial S-PRG(Glass Ionomer with Pre-Activated Surface) (Beautifil II-Shofu Inc.)) were tested. Then, composite resin cylinders were built and, after storage in water for 24 hours, were submitted to shear bond strength evaluation under microtensile bond test. The analysis of the fracture pattern was performed under an optical microscope (40x). The obtained values of shear bond strength (MPa) were submitted to ANOVA (two factors) and Tukey multiple comparisons tests (p<0.05). According to the results, there was no statistically significant difference between substrate interaction and restorative materials (p = 0.711). However, there was a difference between the substrates (p <0.001) and the restorative materials (p = 0.002) evaluated. The values obtained were G1 (47.5 ± 12.2 MPa), G2 (34.1 ± 15.8 MPa), G3 (31.0 ± 8.3 MPa) and G4 (15 , 5 ± 13.6 MPa), with a statistically significant difference in the evaluated substrates and restorative materials. The results, revealed a statistically significant difference in the evaluated substrates and restorative materials. According to the limits of the present study, it was concluded that the bond strength in the eroded substrate is inferior to the sound substrate and that the self-etching adhesive system containing S-PRG(Surface Pre-Reacted Glass) biomaterial results in lower bond strength of the composite resin to the sound or eroded dentin.