Introdução: As características anatômicas dos ossos maxilares e suas possíveis variações apresentam um grande interesse, pela crescente demanda por procedimentos cirúrgicos como cirurgias ortognáticas e colocação de implantes osseointegráveis. Nessa perspectiva, existe particular interesse em relação aos enxertos ósseos autógenos, considerando-se a necessidade crescente de sua aplicação associados aos implantes, naqueles indivíduos com reabsorções e defeitos ósseos. O conhecimento da anatomia e do conteúdo da área inter-forames mentuais e possíveis implicações clínicas são ainda controversos e pouco documentados. A tomografia computadorizada de feixe cônico (TCFC) possibilita a reformatação da imagem em três dimensões permitindo um estudo mais detalhado da região da sínfise mandibular. Objetivo: Avaliar as dimensões da sínfise mandibular para enxertia óssea, nas reformatações panorâmicas e parassagitais obtidas por TCFC. Material e Métodos: Foram determinadas: a distância inter-forames mentuais, a distância entre a cortical vestibular e a cortical lingual e a distância entre o ápice dos dentes anteriores inferiores e a base da mandíbula. Será avaliada também a presença de alças anteriores do nervo mentual e extensão anterior das mesmas nas duas reformatações. Utilizou-se 200 TCFC, de homens e mulheres adultos, proveniente dos arquivos de imagem do Departamento de Estomatologia da Faculdade de Odontologia de Bauru/USP. A visibilidade e as medições da sínfise mandibular foram avaliadas pela TCFC através da ferramenta de distância do i-CAT Vision Software nas reformatações panorâmica (RfPan) e parassagital (RfPsg) determinando assim suas medidas para realização de cirurgia para remoção de enxerto ósseo. Resultados: A média das medidas da distância inter-forames mentuais, para obter a largura da área doadora, foi de 42,27 mm; entre a cortical vestibular externa e a cortical lingual externa, para obter a espessura total da área doadora foi de 10,31 mm para o lado direito, 10,07 mm para o lado esquerdo e 10,5 mm para a linha média; entre a cortical vestibular interna e a cortical lingual interna, para obter a espessura do trabeculado medular da área doadora foi de 5,82 mm para o lado direito, 5,54 mm para o lado esquerdo e 5,93 mm para a linha média; entre o ápice dos dentes anteriores inferiores, preferencialmente os caninos, e a base da mandíbula, para obter a altura da área doadora foi de 13,03 mm para o lado direito, 12,87 mm para o lado esquerdo e 17,86 para a linha média. A alça anterior do forame mentual foi visualizada em 47 das 200 imagens de TCFC, ou 23,5% delas, sendo em 36 (18%) do lado direito e do lado esquerdo, 3 (1,5%) apenas do lado direito e 8 apenas do lado esquerdo (4%). A média das medidas da distância entre a alça anterior e a base da mandíbula foi de 7,02 mm para o lado direito e 6,73 mm para o lado esquerdo. Conclusões: A sínfise mandibular pode fornecer um volume de 632,51 mm3 (32,47 x 4,87 x 4 mm), quando utilizarmos as novas margens de segurança preconizadas, ou até 1.344,13 mm3 (32,47 x 7,87 x 5,26 mm), quando consideradas as margens de segurança previamente descritas. Esses valores mostram a disponibilidade óssea da sínfise mandibular como uma das principais opções para remoção de enxerto autógeno em reconstruções parciais dos maxilares. / Introduction: The anatomical characteristics of the maxillary bones and their possible variations present a great interest by increasing demand for surgical procedures such as orthognathic surgery and placement of osseointegrated implants. From this perspective, there is particular interest in relation to autogenous bone grafts, considering the growing need for their application associated with implants in those individuals with resorption and bone defects. The knowledge of the anatomy and content of the mental inter-foramina area and possible clinical implications are still controversial and poorly documented. Cone beam computed tomography (CBCT) allows reformatting of a three-dimensional image allowing a more detailed study of the mandibular symphysis region. Objective: To assess the dimensions of the mandibular symphysis for bone grafting in panoramic and parasagittal reconstructions obtained by CBCT. Material and Methods: Determined were: the mental inter-foramina distance, the distance between the buccal cortical and lingual cortical and the distance between the apex of the mandibular anterior teeth and the base of the mandibula. The presence of anterior loops of the mental nerve and anterior extension of the same in the two reconstructions will also be evaluated. Two hundred CBCT`s from adult men and women were utilized, obtained from the image files of the Department of Stomatology, Bauru School of Dentistry / USP. The visibility and measurements of the mandibular symphysis were evaluated by CBCT through the distance tool from the i-CAT Vision Software in panoramic (RfPan) and parasagittal (RfPsg) reconstructions, thus determining their measurements to perform surgery for the removal of the bone graft. Results: The average measurement of the mental inter-foramina distance, to obtain the width of the donor area was 42.27 mm between the outer buccal cortical and external lingual cortical, and to obtain the total thickness of the donor area was 10.31 mm to the right side, 10.07 mm to the left side and 10.5 mm to the midline; between the internal buccal cortical and internal lingual cortical to obtain the thickness of the trabecular medullary of the donor area was 5.82 mm to the right side, 5.54 mm to the left side and to 5.93 mm to the midline, between the apex of the anterior teeth, preferably canines and the base of the mandibula to obtain the height of the donor area was 13.03 mm to the right side, 12.87 mm to the left and 17.86 to the midline. The anterior loop of the mental foramen was visualized in 47 out of 200 CBCT images, or 23.5%, and in 36 (18%) of the right and left sides, 3 (1.5%) only on the right side and 8 only the left side (4%). The average measure of the distance between the anterior loop and the base of the mandibula is 7.02 mm to the right side and 6.73 mm to the left side. Conclusions: The mandibular symphysis can provide a volume of 632.51 mm3 (32.47 x 4.87 x 4 mm), when the new recommended safety margins are used, or until 1344.13 mm3 (32.47 x 7.87 x 5.26 mm), when considering the safety margins previously described. These values show the available bone of the mandibular symphysis as one of the main options for removal of the autogenous graft in partial maxillary reconstructions.

Este estudo avaliou, quantitativamente, o osso regenerado após técnica de regeneração óssea guiada, utilizando osso autógeno em bloco e membrana de colágeno e descreveu seu processo de reparação ao redor de superfícies de implantes usinadas ou tratadas por jato de óxido de titânio em períodos de até 150 dias. Foram utilizados 60 ratos machos Wistar, divididos em 2 grupos: um recebeu implantes com superfície usinada (U) e o outro recebeu implantes com superfície tratada por jato de óxido de titânio (T). Uma trefina foi utilizada para a remoção do enxerto ósseo em bloco da calvária do animal. O enxerto foi fixado próximo ao ângulo da mandíbula do rato, na cortical vestibular, com o uso do implante. O conjunto foi coberto por membrana de colágeno. A ortotanásia foi realizada em 0, 14, 21, 45 e 150 dias. Foi realizado processamento histológico para material nãodescalcificado, e um corte no longo eixo do implante foi obtido para cada espécime. Foram realizadas análises qualitativa e quantitativa. Os dados foram analisados estatisticamente, em um nível de significância de 5%, pelos testes de Kruskal-Wallis e de Dunn. Os resultados relativos aos períodos de observação mostraram que a média do tamanho do defeito inicial foi de DO-U = 604,13 m e DO-T = 585,90 m (p=0,720) e que a média de espessura inicial do leito foi de EL-U = 257,29 m e ELT = 243,57 m (p=0,07); houve uma redução da espessura do enxerto no período de 150 dias para o grupo T em relação ao grupo U (EE-T = 338,25 m; EE-U = 407,71m) (p=0,003), não havendo outras diferenças significativas entre os grupos. Notou-se a presença de osso regenerado, vestibularmente ao enxerto, a partir de 21 dias, com uma nítida tendência ao aumento de sua espessura até o período de 150 dias, onde notamos um aumento da espessura óssea total de cerca de 4,6 (T) e 4,8 (U) vezes a espessura original da mandíbula, com valores de ETTO U = 1254,40 m e ETTO T = 1141,85 m (p=0,48). / This study quantitatively analyzed the regenerated bone after guided bone regeneration technique using autogenous block graft with resorbable membrane and described its pattern around machined titanium or oxide grit-blasted titanium surfaces in periods of up to 150 days. Sixty male, adult, Wistar rats were randomly assigned to one of two groups: machined titanium surface (U) or oxide grit-blasted titanium surface (T). A block graft was harvested from the rat calvarium with a trephine, laid and stabilized on the external cortex near the angle of the mandible with implants. A collagen membrane was adapted to completely cover the bone graft in both groups. The animals were euthanized at 0, 14, 21, 45 and 150 days after surgery. Nondecalcified histological sections were processed for each specimen and one section on the long axis of the implant was obtained. Qualitative and quantitative analysis were carried out. Statistical analyses were carried out with a significance level of 5% and used Kruskal-Wallis and Dunn tests. Results showed that the mean bone defect was DO-U = 604,13 m and DO-T = 585,90 m (p=0,720), and the mean mandible bone width was EL U = 257,29 m and EL-T = 243,57 m at zero hour. The mean graft width was reduced after 150 days for the T group as compared to group U (EET = 338,25 m and EE-U = 407,71 m) (p=0,003). No other significant differences between groups were observed. Regenerated bone was observed buccal to the bone graft after 21 days increasing in width after 150 days. The final mean mandible bone width after 150 days (ETTO-U = 1254,40 m and ETTO-T = 1141,85 m) achieved 4,8 (U) and 4,6 (T) times the original mandible width (p=0,48).

Objetivo: Avaliar o controle da supuração de cavidades mastoideas após cirurgia revisional e obliteração de mastoide com aloenxerto ósseo particulado congelado (AOPC). Desenho do estudo: Exploratório, prospectivo, tipo série de casos. Pacientes: Dez adultos selecionados entre pacientes já submetidos à cirurgia de mastoidectomia cavidade aberta ou fechada para tratamento de otite média crônica colesteatomatosa e que tinham indicação de cirurgia revisional. Intervenção: Revisão de mastoidectomia e obliteração da cavidade com AOPC, material de preenchimento de baixo custo obtido de um banco de tecidos. Desfecho(s): Desfecho primário: controle da supuração. Desfechos secundários incluem: integração do AOPC na cavidade mastoidea, presença de colesteatoma residual ou recorrente, resultados audiológicos, complicações pós-operatórias, tais como infecção e extrusão do enxerto, e qualidade de vida após o procedimento medida com a escala de resultados de Glasgow (ERG). Resultados: O tempo médio de seguimento foi de 28 meses. Sete pacientes apresentaram o ouvido seco, em média, 8 semanas após a cirurgia. Três pacientes desenvolveram exposição do enxerto ósseo seguido de infecção e extrusão do material de preenchimento. A densidade média do enxerto ósseo no local da obliteração foi de 755.35 unidades Hounsfield medida na tomografia realizada após um tempo médio pós-operatório de 31 meses. A porcentagem do volume mastoideo obliterado foi de 75 a 100% em 6 casos e de 50 a 75% em 1 caso. Nos 7 pacientes, houve um aumento na densidade óssea durante o período de seguimento. Um paciente apresentou colesteatoma epitimpânico recorrente (0,5cm) identificado na ressonância magnética 1 ano após a cirurgia, embora este não estivesse na área de obliteração. A audição foi preservada em 80% dos pacientes 12 meses após o procedimento. A qualidade de vida melhorou em todos os pacientes, com média do escore ERG de 52, em escala que varia de -100 a +100. Conclusões: Este estudo demonstrou que o AOPC pode ser usado como material de preenchimento na obliteração mastoidea para se obter um ouvido seco, apresentando boa integração na mastoide e manutenção da densidade óssea / Objective: Assess the control of suppuration after revision surgery with mastoid obliteration for chronic otitis media (COM) with cholesteatoma using particulated frozen allograft bone (PFAB). Study Design: Exploratory, prospective, case series. Patients: Ten adults were selected from among patients who had undergone canal wall down or canal wall up mastoidectomy for COM with cholesteatoma, and had an indication for revision surgery. Intervention(s): Revision mastoidectomy with obliteration of the open cavity was performed with PFAB, a low-cost filler material obtained from a tissue bank. Main Outcome Measure(s): The main outcome measure was the control of suppuration. Secondary outcome measures included PFAB integration in the mastoid cavity, presence of recurrent or residual cholesteatoma, hearing outcomes, postoperative complications as infection and bone graft extrusion and quality of life after the procedure using the Glasgow benefit inventory (GBI) survey. Results: Mean follow-up was 28 months. Seven patients achieved a dry ear at a mean of 8 weeks postoperatively. Three patients developed bone graft exposure followed by infection and extrusion of the filler material. Mean bone density was 755.35 Hounsfield units at the obliteration site measured at computed tomography performed after a mean of 31 months postoperatively. Percentage of mastoid volume obliterated was between 75% and 100% in 6 cases and between 50% and 75% in 1 case. In all 7 patients, there was an increase in bone density postoperatively. One patient presented with recurrent epitympanic cholesteatoma (0.5 cm) at 1 year postoperatively, but it was not in the obliteration area. At 12 months postoperatively, 80% of patients had preserved hearing. All patients had an improvement of quality of life after mastoid obliteration, the average score on the GBI was 52 in a scale from -100 to +100. Conclusions: This study demonstrated that PFAB may be used to achieve a dry mastoid cavity with good bone graft osteointegration and density maintenance

Buscando alternativas ao enxerto ósseo autógeno para reconstruções craniofaciais, propõe-se a utilização de aloenxerto ósseo de crânio criopreservado, irradiado e enriquecido com medula óssea autógena.Vinte e um coelhos foram sacrificados e tiveram seus ossos parietais retirados, criopreservados e irradiados com irradiação gama em dose de 50kGy. Os aloenxertos foram implantados em defeitos nos crânios de vinte e um receptores. À esquerda implantava-se o aloenxerto ósseo puro e à direita o aloenxerto adicionado de medula óssea autógena. Os coelhos foram sacrificados em duas, cinco e dez semanas e os enxertos submetidos à análise macroscópica e histomorfométrica. Todos os enxertos apresentavam-se fixos ao leito. Os parâmetros histomorfométricos não mostraram diferenças estatisticamente significante. / Searching for alternatives to autogenous bone graft in craniofacial reconstructions, it is proposed deep-frozen, irradiated calvarial bone allograft added with autogenous bone marrow utilization. Twenty and one rabbits were sacrificed and their parietal bones harvest, deep-frozen and gamma irradiated with 50kGy. The allografts were implanted in twenty one other rabbits. At left side only allograft were placed, at right side were put allografts added with autogenous bone marrow. The animals were sacrificed in two, five and ten weeks. Macroscopical examination showed all grafts fixed at the host bone, the histomorphometric analysis did not showed significant statistical differences between the left and right sides.

Desde os primórdios da Medicina, a grande preocupação do profissional era ser humanista, com conhecimento cultural, sociológico, familiar, psicológico e espiritual do seu paciente. Durante a primeira metade do século XX, houve uma verdadeira explosão de novas técnicas operatórias e de evoluções no campo tecnológico, principalmente durante e logo após as duas grandes guerras mundiais. Novas especialidades, dentre essas a Cancerologia e suas subdivisões, iniciaram técnicas próprias de tratamento cirúrgico. Desde então, os tratamentos impulsionaram a realização de novos métodos de reconstrução dos defeitos produzidos pelas cirurgias, cada vez mais invasivas e mutiladoras. Portanto, além do diagnóstico e tratamento das enfermidades, começou a existir a preocupação com o resultado destes, como o tipo de contribuição e resultados funcionais para o paciente. Nas últimas décadas, houve a necessidade de avaliar a Qualidade de Vida (QV) destes pacientes frente aos tratamentos realizados. As neoplasias malignas de cabeça e pescoço, pela própria localização anatômica, podem acarretar alterações significativas em funções vitais relacionadas à alimentação, comunicação e interação social dos indivíduos afetados. Objetivo: Avaliar a qualidade de vida dos pacientes com neoplasias malignas avançadas de cavidade oral submetidos a operações radicais com intenção curativa, comparando um grupo de pacientes submetidos à reconstrução funcional de mandíbula com um grupo de pacientes nos quais esta reconstrução não foi efetuada. Material e métodos: 47 pacientes matriculados na Seção de Cirurgia de Cabeça e Pescoço do Hospital do Câncer (HCI-INCa), portadores de carcinoma espinocelular (CEC) de cavidade oral, em estádios III e IV, foram submetidos ao tratamento cirúrgico com mandibulectomia segmentar e radioterapia complementar. Todos foram submetidos ao teste de Qualidade de Vida após o tempo mínimo de seis meses do tratamento cirúrgico. A maioria tinha como sitio anatômico da lesão primária mucosa jugal (49%), seguido do rebordo gengival (33%). As avaliações dos dados colhidos foram analisadas utilizando valores médios, medianas, desvios padrões, frequências simples e percentuais. A avaliação foi feita comparando os tipos de reconstrução: pacientes submetidos a mandibulectomia sem reconstrução funcional da mandíbula (Grupo 1) e com reconstrução funcional da mandíbula (Grupo2). O teste aplicado foi o da Universidade de Washington (UW-QOL). Resultados: Inicialmente, foram selecionados 183 pacientes, contudo em apenas 47 (25,7%) pacientes foi possível a realização da entrevista, sendo estes a amostra para o estudo. A maioria dos pacientes do grupo selecionado era do sexo masculino, total de 39 homens (82,9%). A idade média foi de 64,4 anos (25-94 anos). A maioria dos pacientes apresentava estadiamento clínico IV (83%), foram submetidos à radioterapia adjuvante (95,4%). Treze (27,65%) pacientes receberam reconstrução funcional da mandíbula (grupo 2). A média do escore obtido após a avaliação dos questionários foi de 64,6 (50 a 86,83), a média do escore do Grupo 1 foi de 65 e do Grupo 2 foi de 63,1. Os piores escores foram encontrados nos quesitos deglutição ( Grupo 1 escore de 54,13 e Grupo 2 escore de 53,92) e mastigação (Grupo 1 escore de 25 e Grupo 2 escore de 23,08). Não houve diferenças estatisticamente significativas em nenhum quesito quando comparamos os dois grupos. Pacientes com estadiamento clínico III apresentaram a variável idade na data da entrevista mostrou significância clínica e estatística no domínio dor (p=0,049), evidenciando que pacientes com mais de 60 anos relatavam melhor escore do que os com idade inferior a 60 anos na data da entrevista. A situação conjugal foi estatisticamente associada à qualidade de vida no domínio saliva (p=0,045) e clinicamente, nos domínios aparência e ombro. Pacientes com estadiamento clínico III apresentaram clinicamente melhores escores do que os com estádio IV, evidenciando significância estatística no domínio recreação (p = 0,034). Os pacientes com mais de dois anos de tempo transcorrido entre a cirurgia e a entrevista apresentaram melhores escores de qualidade de vida dos que os com menos de dois anos, com significância estatística para os domínios dor (p=0,032), recreação (p=0,034), fala (p=0,046), paladar (p=0,009), ansiedade (p=0,011) e escore composto. Pacientes com menos de 2 anos de tratamento apresentaram pior escore composto, único quesito com significância estatística entre os grupos (p=0,023). Conclusão: Não houve diferenças estatisticamente significativas nos domínios de Qualidade de Vida entre os dois grupos estudados (com reconstrução óssea versus sem reconstrução óssea), pacientes entrevistados 2 anos ou mais após o tratamento apresentaram escores superiores (p=0,023), único dado com diferença estatisticamente significativa / Since the beginning of Medicine, the major concern of the professional was to be humanist, having cultural, sociological, family-related, psychological and spiritual knowledge of his patient. During the first half of the twentieth century there was an explosion of new surgical techniques and developments in the technological field, especially during and after the two world wars. New specialties, among these the Oncology and their subdivisions initiated proper techniques of surgical treatment. Since then the treatments have boosted the implementation of new methods of reconstruction of defects produced by surgery, increasingly invasive and mutilating, therefore, in addition to the diagnosis and treatment of diseases, came into being the concern about the outcome of these, such as the type of contribution and functional results for the patient. Over the last decades there was a need to assess the Quality of Life (QL) of these patients compared to the treatments performed. Malignant neoplasms of the head and neck, by their own anatomical location, may entail significant changes in vital functions related to feeding, communication and social interaction of the affected individuals. Objective: Assessing the quality of life of patients with advanced malignant neoplasms of the oral cavity undergoing radical operations with curative interaction, comparing a group of patients undergoing functional reconstruction of the jaw with a group of patients in whom this reconstruction was not performed. Material and methods: A total of 47 patients enrolled in the Head and Neck Surgery Section of the Cancer Hospital (HCI-INCA). Carriers of squamous cell carcinoma (SCC/CEC) of the oral cavity, in stages III and IV., were submitted to surgical treatment with segmental mandibulectomy and complementary radiotherapy. All were submitted to the Quality of Life test after a minimum period of six months from the surgery. Most had the anatomical site of primary buccal mucosa (49%), followed by gingival border (33%). The assessment of the data collected was analyzed using averages, medians, standard deviations, simple frequencies and percentages. The evaluation was made by comparing the types of reconstruction: patients undergoing mandibulectomy without functional reconstruction of the jaw (Group 1) and functional reconstruction of the jaw (Group 2). The test used was the University of Washington (UW-QOL). Outcome: Initially, 183 patients were selected, but with only 47 (25.7%) patients the interview was possible, which are the sample for the study. Most of the selected group of patients were male, total 39 men (82.9%). The average age was 64.4 years (25-94 year-old). Most of the patients had clinical stage IV (83%), underwent adjuvant radiotherapy (95.4%). Thirteen (27.65%) patients had functional reconstruction of the mandible (Group 2). The mean score obtained after the evaluation of the questionnaires was 64.6 (50 to 86.83), Group 1\'s average score was 65 and Group 2 was 63.1. The worst scores were found in swallowing (Group 1 score of 54.13 and Group 2 score of 53.92) and chewing questions (Group 1 score of 25 and Group 2 score of 23.08). There were no statistically significant differences in any question when we compare the two groups. Patients with clinical stage III presented a variable age at the interview showed clinical and statistical significance in the pain domain (p = 0.049), showing that patients older than 60 years reported better score than under the age of 60 years at the interview. Marital status was statistically associated with quality of life in the saliva domain (p = 0.045) and clinically in the fields appearance and shoulder. Patients with clinical stage III showed clinically better scores than those with stage IV, showing statistical significance in the recreation area (p = 0.034). Patients with more than two years of time between surgery and the interview have better quality of life scores than those with less than two years, with statistical significance for the pain domain (p = 0.032), recreation (p = 0.034 ), speech (p = 0.046), taste (p = 0.009), anxiety (p = 0.011) and composite score. Patients younger than 2 years of treatment had worse composite score, only question statistically significant between groups (p = 0.023). Conclusion: There were no statistically significant differences in the areas of quality of life between the two groups (with bone reconstruction versus without bone reconstruction), patients interviewed two years or more after treatment had higher scores (p = 0.023), only data showing a statistically significant difference

Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle mineral component in bone. This dissertation describes the development of smart bone tissue engineering scaffolds composed of the biodegradable amphiphilic polymer poly(D,L-lactic acid-co-ethylene glycol-co- D,L-lactic acid) (PELA) and HA. Electrospun nanofibrous HA-PELA scaffolds exhibited improved handling characteristics and bioactivity over conventional HApoly( D,L-lactic acid) composites. Electrospun HA-PELA was hydrophilic, elastic, stiffened upon hydration, and supported the attachment and osteogenic differentiation of rat bone marrow stromal cells (MSCs). These in vitro properties translated into robust bone formation in vivo using a critical-size femoral defect model in rats. Spiral-wrapped HA-PELA scaffolds, loaded with MSCs or a lowdose of recombinant human bone morphogenetic protein-2, templated bone formation along the defect. As an alternate approach, PELA and HA-PELA were viii rapid prototyped into three-dimensional (3-D) macroporous scaffolds using a consumer-grade 3-D printer. These 3-D scaffolds have differential cell adhesion characteristics, swell and stiffen upon hydration, and exhibit hydration-induced self-fixation in a simulated confined defect. HA-PELA also exhibits thermal shape memory behavior, enabling the minimally invasive delivery and rapid (>3 sec) shape recovery of 3-D scaffolds at physiologically safe temperatures (~ 50ºC). Overall, this dissertation demonstrates how the rational selection of FDA approved materials with synergistic interactions results in smart biomaterials with high potential for clinical translation.

Injury to bone is one of the most prevalent and costly medical conditions. Clinical treatment of volumetric bone loss or hard-to-heal bony lesions often requires the use of proper bone grafting materials, with or without adjuvant anabolic therapeutics. Despite significant problems associated with autografting (donor site morbidity, limited supplies) and allografting (disease transmissions, high graft failure rates) procedures, synthetic bone grafts remain the least utilized clinically. Existing synthetic orthopaedic biomaterials rarely possess a combination of bone-like structural and biochemical properties required for robust osteointegration, scalable and user-friendly characteristics indispensable for successful clinical translations. This thesis tests the hypothesis that by recapitulating key structural elements and biochemical components of bone in 3- and 2-dimensional biomaterials, scalable synthetic bone grafts can be designed to enable expedited healing of hard-to-heal volumetric bone loss. Specifically, FlexBone, a 3-dimensional hydrogel scaffold encapsulating 50 wt% of structurally well integrated nanocrylstalline hydroxyapatite, the main inorganic component of bone, was developed. The large surface area of nanocrystalline hydroxyapatite combined with its intrinsic affinity to proteins and its excellent structural integration with the hydrogel matrix enabled FlexBone to both sequester endogenous protein signals upon press-fitting into an area of skeletal defect and to deliver exogenous protein therapeutics in a localized and sustained manner. We demonstrated that FlexBone enabled the functional healing of critical-size long bone defects in rats in 8 – 12 weeks with the addition of a very low dose of osteogenic growth factor BMP-2/7. This promising synthetic bone graft is now being explored for the delivery of multiple growth factors to expedite the healing of diabetic bony lesions. In addition, a 2-dimensional electrospun cellulose fibrous mesh was chemically modified with sulfate residues to mimic sulfated polysaccharide ECM components of skeletal tissues to enabled progenitor cell attachment and differentiation as well as controlled retention and localized/sustained delivery of protein therapeutics. This sulfated fibrous mesh is currently explored as synthetic periosteum to augment the osteointegration of devitalized structural allografts. Finally, a rat subcutaneous implantation model developed to examine the biocompatibility of newly developed biodegradable shape memory polymer bone substitutes is also presented.

[Truncated abstract] Around 50,000 hip and knee replacements are performed every year in Australia and this number has been increasing by around 13% annually since 1998 (Transplantation Society 2006). The incidence and number of revision surgery has increased by a similar proportion. Autogenous bone or allograft is still the gold standard grafting material and is currently used in a variety of reconstructive surgical procedures. The use of any allograft material carries with it the risk of transfer of disease from donor to recipient. These tissues can transmit the same viral and bacterial infections as blood, and the products of a single donation may be transplanted to several recipients. In contrast to blood, musculoskeletal tissues may come from surgical and cadaveric donation. Overall, the prevention of infection relies on the maintenance of rigid protocols for procurement, donor and allograft testing, secondary sterilisation, and the adherence to internal safety standards within the tissue banks. This thesis aims to determine the risk of viral infection among musculoskeletal tissue donors in Australia. We retrieved and analysed data retrospectively from three large tissue banks in Australia (Perth, Queensland, Victoria). This includes 12,415 musculoskeletal tissue donors, 10,937 of which are surgical donors and 1,478 of which are deceased donors, for the period of 1993 -2004. This data was analysed to determine the prevalence and incidence of viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) in musculoskeletal allografts. The results indicate that the risk of viral infection from musculoskeletal tissue transplantation in Australia is low. ... The results indicate that the overall prevalence of screened transfusion-transmitted viral infections did not vary significantly for musculoskeletal donors over the study period, despite falling in the general population and first-time blood donors. In tissue donors, HIV incidence significantly decreased over time, and HBV decreased significantly during 1999-2001; however, there was an apparent increase in the estimated incidence of HCV in 2002-2004 compared with earlier years. Furthermore the residual risk estimate of HIV in the period 2002-2004 has declined 5-fold compared to estimates in the period 1993-1995. This is perhaps due to greater awareness of high risk behaviours among donors, improvement in donor recruitment and an overall decrease in infection levels in the general population. Musculoskeletal tissue is second only to blood as the most frequent transplanted human tissue. Viral infection is a potential complication of tissue transplantation. In this thesis the rates of HIV, HBV, HCV and HTV infection in musculoskeletal donors in Australia were identified and then compared with results in published data from Canada, Scotland and the United States. The study also compared that result with first-time blood donors because they have satisfied similar donor selection criteria (Galea et al. 2006). The results indicate that prevalence and incidence estimates for viral infection in Australian tissue donors are higher than those in blood donors. This was also reported in studies from other countries. Accordingly, it is crucial that viral prevalence and incidence be monitored to evaluate the safety of tissue supply and to improve donor selection processes.

Made available in DSpace on 2015-07-22T20:50:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-01-26. Added 1 bitstream(s) on 2015-08-11T03:26:03Z : No. of bitstreams: 1 Publico-12529a.pdf: 1382817 bytes, checksum: 65bd98549521fbf2650836a170f9761e (MD5). Added 1 bitstream(s) on 2015-08-11T03:26:03Z : No. of bitstreams: 2 Publico-12529a.pdf: 1382817 bytes, checksum: 65bd98549521fbf2650836a170f9761e (MD5) Publico-12529b.pdf: 1113563 bytes, checksum: 3261d75b2356f849d087c69443322b57 (MD5) / As BMPs, proteínas indutoras de crescimento ósseo, desde o início de sua utilização têm sido avaliadas em diferentes modelos experimentais objetivando determinar sua eficácia. Sabemos que algumas substâncias podem interferir positiva ou negativamente quando utilizadas de forma sistêmica ou local, associadas à BMP. Objetivo: Este estudo tem por objetivo avaliar as possíveis interferências da utilização de antibioticoterapia profilática pré e pós-operatória, utilizando-se como princípio ativo a cefazolina, aplicada a um modelo experimental em coelhos. Métodos: Foram utilizados dois grupos de coelhos fêmea, neozelandeses, submetidos à artrodese intertransversa da coluna lombar, segmento L5-L6, por via posterior. No primeiro grupo foi utilizado o enxerto autólogo associado ao biocomposto (BMP bovino, 1,0mg e hidroxiapatita, 9,0mg). No segundo grupo foi realizado o mesmo procedimento e utilizado o mesmo biocomposto, porém os animais foram submetidos a antibioticoterapia profilática com cefazolina iniciada duas horas antes e mantida por 24 horas após o término do procedimento. Os animais foram acompanhados por 15 semanas, isolados em cativeiro e avaliados diariamente por veterinário sob o ponto de vista clínico e neurológico, sendo posteriormente sacrificados e retiradas as peças cirúrgicas para serem submetidas à análise radiográfica e histológica. Resultados: Para o grupo 1, a quantidade e localização do material implantado variaram entre os indivíduos, porém, na maioria dos casos (6 amostras), a quantidade de partículas de osso homólogo era insignificante e estava dispersa ao longo do tecido mole que recobre o dorso da vértebra, circundado por tecido reacional com área de necrose. Nos demais casos as partículas com reabsorção preenchiam o reduzido espaço entre os processos transversos. Para o grupo 2, a quantidade do material e sua localização também variaram entre os indivíduos. Na maioria dos casos inúmeras partículas de osso mole preenchiam o espaço entre os processos laterais cuja neoformação óssea levou ao aprisionamento de algumas dessas partículas. Todos os casos exibiram formação em maior ou menor intensidade de tecido cartilaginoso na superfície dos processos transversos. A análise radiográfica mostrou em sua freqüência relativa maior freqüência de fusão completa para o grupo 2 quando comparado ao grupo 1. Conclusão: Do ponto de vista histológico para o modelo e período experimental analisado, inferimos que, embora nenhum dos tratamentos propostos tenha promovido o completo fusionamento das vértebras por tecido ósseo, a utilização de osso homólogo + BMP bovina, associada à aplicação de cefazolina, promoveu maior formação cartilaginosa e óssea com menor índice de rejeição do material enxertado na área doadora, quando comparada ao grupo sem associação de cefazolina. Do ponto de vista radiográfico, a análise relativa também demonstrou-se superior para o grupo onde foi utilizado cefazolina. / The BMPs, the inductive proteins of bone growth since the beginning of their use have been evaluated in different experimental models aiming to determine their efficacy. We know that some substances can interfere positively or negatively when used in a systemic way or places associated with the BMP. Objective: this study objective to evaluate the possible interferences of antibiotic-therapy by using the active principle of cefazolin in an experimental model with rabbits. Methods: Two groups of female New Zealand rabbits underwent a lumbar spine inter-transverse artrodesys of segment L5-L6 using posterior approach. An homolog bone graft associated with a bio-compound (bovine BMP, 1,0mg and hydroxiapatita, 9,0mg) was used in the first group. The same procedure and bio-compound were used in the second group. However the animals were submitted to a prophylactic antibiotic-therapy with cefazolin starting two hours before the procedure and maintained for 24 hours after surgery. The animals were analyzed for 15 weeks, isolated in captivity and daily evaluated by a veterinarian under the clinical and neurological views and then euthanized, being the surgical pieces removed and submitted to a radiological and histological analysis. Results: For the first group the quantity and location of the implanted material varied among the individuals. However in most of the cases, the quantity and particles of homolog bone was insignificant and disperse along the soft tissue that covers the posterior region of the vertebrae. In the other cases, the particles with reabsorvation filled the reduced space between the transversal processes. For the second group, the quantity of material and its location also varied among the individuals. In most of the cases, several particles of homolog bone filled the space between the lateral processes whose bone neo-formation led to a trapping of these particles. All the cases showed formation in a higher or lower intensity of the cartilaginous tissue in the surface of the transverse processes. The radiological analysis showed in its relative frequency a higher frequency of complete fusion for group 2 when compared to group 1. Conclusion: Under the histological view for the model and experimental period analyzed, we inferred that, despite the fact that none of the proposed treatments had promoted a complete fusion of the vertebraes per bone tissue, the use of homolog bone + bovine BMPs associated with the use of cefazolin promoted a higher cartilaginous and bone formation with lower incidence of rejection of the material grafted in the doer area when compared to the group without the association of cefazolin. Under the radiological view, the relative analysis also showed to be superior in the group where cefazolin was used as a prophylactic antibiotic. / TEDE / BV UNIFESP: Teses e dissertações