Atualmente existe uma lacuna de conhecimento referente à doação e ao transplante do tecido ósseo, já que muitas publicações concentram-se, principalmente, na temática \'doação e transplante de órgãos sólidos\'. O objetivo deste estudo foi compreender os aspectos intervenientes na efetivação da doação do tecido ósseo durante o acolhimento e a entrevista familiar, realizada pelos profissionais da Organização de Procura de Órgãos, na ótica do profissional e do familiar do potencial doador. Método: Este estudo de abordagem qualitativa, apoiado em conceitos do interacionismo simbólico, constituiu-se de familiares de doadores de órgãos e tecidos que autorizaram a doação do tecido ósseo no período de janeiro a dezembro de 2016, iniciando-se a partir de pesquisa nos prontuários da Organização de Procura de Órgãos localizada no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto/SP. Selecionaram-se todos os prontuários dos doadores de tecido ósseo, totalizando doze doadores Ainda, foram convidados a participar do estudo os quatro enfermeiros responsáveis pelo acolhimento e entrevista para solicitação dos órgãos e tecidos pertencentes à Organização de Procura dos Órgãos citada, por meio de uma entrevista gravada e realizada em seu contexto de trabalho. Foram entrevistados nove familiares e quatro enfermeiros mediante roteiro de entrevista contendo dados sociodemográficos e questões sobre a vivência de todo o processo de doação do tecido ósseo. O material foi transcrito e submetido a análise de conteúdo indutiva em três categorias temáticas: contexto onde se dá o processo de solicitação da doação, fatores que facilitaram a decisão pela doação do tecido ósseo e o resultado do processo de doação para o familiar. Observamos que os familiares, ao refletirem sobre o momento de decisão pela doação do tecido ósseo, revelaram que, apesar do desconhecimento desse tipo de doação, os aspectos que contribuíram para o consentimento foram a satisfação com o atendimento hospitalar humanizado, bem como o profissionalismo dos enfermeiros da Organização de Procura de Órgãos ao explicarem quais ossos seriam retirados e como seria reconstituído o corpo do doador; o conhecimento prévio da vontade do ente querido em ser um doador e o pensamento de estar \"fazendo o bem\". Observamos ainda que os enfermeiros, ao refletirem sobre seu papel na entrevista para solicitação da doação do tecido ósseo, revelaram que, inicialmente, o desconhecimento dos familiares quanto à possibilidade de doação do tecido ósseo, faz com que os mesmos reajam negativamente devido ao medo da deformidade do corpo. Objetivando superar esse momento difícil, os enfermeiros explicam todo o processo de captação do tecido ósseo, até a forma como seria entregue o corpo do familiar para o velório. Sugerem-se capacitações futuras à equipe de enfermeiros contribuindo para a otimização de todo o processo de doação do tecido ósseo para transplante. Acreditamos ser evidente a necessidade de educação voltada à população por meio de ações governamentais, em que futuras campanhas na divulgação da existência da doação do tecido ósseo possam promover um maior entendimento, resultando em uma reação menos traumática das pessoas no momento da solicitação do tecido ósseo / Currently there is a lack of knowledge regarding donation and transplantation of bone tissue, due many publications to focus primarily on donation and transplantation of solid organs. The aim of this study was to understand the intervening aspects on the effectiveness of bone tissue donation during approach and family interview, carried out by professionals of the Organ Procurement Organization, from perspective of professionals and potential donor relatives. Methods: It is a qualitative study, based on symbolic interactionism concepts; the sample was composed for relatives of donors of organs and tissues that authorized the donation of bone tissue in the period from January to December of 2016,.The first part was characterized for a data collection in the medical records from Organ Procurement Organization located in a Brazilian School Hospital. There were twelve donors during the selected period which medical records were selected to analyze. In addition, four nurses belonging to Organ Procurement Organization were invited to participate in study. They were responsible for the approach and interview with relatives to request organs. The data collection strategy was a structured interview which was recorded and performed in their workplace. Nine families and four nurses were interviewed using an interview script containing sociodemographic data and questions about the experience of entire process of donating bone tissue. The interviews were transcribed and submitted to analysis of inductive content in three thematic categories: the context where the donation request process happens, factors that facilitated the decision by the donation of the bone tissue and the donation process result to the relative. Results: It was observed that family members reflected on the moment of decision of bone tissue donation. They revealed that, despite the lack of knowledge about this type of donation, there were some aspects that contributed to the consent satisfaction with humanized hospital care as well as the nurses of the Organ Procurement Organization professionalism. These nurses explained which bones would be removed and how the donor\'s body would be reconstituted. Another contributed factor was the relatives prior knowledge of the being´s desire to be an organ donor and the \"doing good\" feeling. Meanwhile, the nurses interviewed revealed that initially there was family members\' lack of knowledge about the possibility of donation of the bone tissue, causes them to react negatively due to the fear of deformity of the body. The nurses explained the whole process of bone tissue withdrawal and the way which the deceased´s body would be delivered to the funeral. The aims of this approach were to overcome this difficult moment and family insecurity to make decision. Conclusions: Future nurses team training is suggested to improve all bone tissue donation for transplantation process. It is extremely important a population-oriented education through governmental actions, campaigns about bone tissue donation to promote a better understanding. It could result in less traumatic people reaction at the moment of bone tissue demand

This thesis, comprising 5 separate studies, is concerned with fixation of prosthetic components in total hip arthroplasty. The results and conclusions of the studies fol-low; The initial stability of femoral revision components, the long cementless PCA stem and the Exeter standard stem cemented in a bed of impacted bone graft, was com-pared in an experimental study. The PCA stem was more stable than the Exeter stem. However, for both stems initial stability may not be sufficient to allow bone ingrowth. Initial fixation is especially vulnerable to torsion. Identical femoral stems with or without HA-coating were compared in a prospec-tive randomized clinical trial. The long-term stable fixation of a cementless Link RS femoral component was improved by application of hydroxyapatite coating to the femoral stem. In a clinical study the method of extensive impaction of morsellized bone allograft and a hydroxyapatite-coated cementless Mallory-Head acetabular component was found to be advantageous for acetabular revision in the presence of contained or acetabular wall defects. The limited contact between the HA-coated implant and living host bone did not seem to compromise long-term stable fixation. Two different cup designs were compared in a prospective randomized RSA study. At 3 years after implantation the cemented low profile Lubinus FAL cup performed as well as the cemented Lubinus Standard cup in terms of migration and polyethyl-ene wear. In a study of the relationship between radiolucent lines and migration the Lubinus FAL cup displayed more radiolucent lines in the cement bone interface than the Lubinus Standard cup but no difference in migration was found. Early appearance of such radiolucent lines represents an unspecific finding without reliable correla-tion to 3-year migration of the acetabular component.

Bone defects and fracture non-unions remain a substantial challenge for clinicians due to a high occurrence of delayed union or non-union requiring surgical intervention. The current grafting procedures used to treat these injuries have many limitations and further long-term complications associated with them. This has resulted in research efforts to identify graft substitution therapies that are able to repair and replace tissue function. Many of these tissue engineered products include the use of growth factors to induce cell differentiation, migration, proliferation, and/or matrix production. However, current growth factor delivery methods are limited by poor retention of growth factors upon implantation resulting in low bioactivity. These limiting factors lead to the use of high doses and frequent injections, putting the patients at risk for adverse effects. The goal of this work was to develop and evaluate the efficacy of BMP-2 delivery systems to improve bone regeneration. We examined two approaches for delivery of BMP-2 in this work. First, we evaluated the use of a self-assembling lipid microtube system for the sustained delivery of BMP-2. We determined that sustained delivery of BMP-2 from the lipid microtube system was able to enhance osteogenic differentiation compared to empty microtubes, however did not demonstrate a significant advantage compared to a bolus BMP-2 dose in vitro. Second, we developed and assessed the functionality of an affinity-based system to sequester BMP-2 at the implant site and retain bioactivity by incorporating heparin within a collagen matrix. Incorporation of heparin in the collagen matrix improved BMP-2 retention and bioactivity, thus enhancing cell-mediated mineralized matrix deposition in vitro. Lastly, the affinity-based BMP-2 delivery system was evaluated in a challenging in vivo bone repair model. Delivery of pre-bound BMP-2 and heparin in a collagen matrix resulted in new bone formation with mechanical properties not significantly different to those of intact bone. Whereas delivery of BMP-2 in collagen or collagen/heparin matrices had similar volumes of regenerated mineralized tissue but resulted in mechanical properties significantly less than intact bone properties. The work presented in this thesis aimed to address parameters currently preventing optimal performance of protein therapies including stability, duration of exposure, and localization at the treatment site. We were able to demonstrate that sustained delivery of BMP-2 from lipid microtubes was able to induce osteogenic differentiation, although this sustained delivery approach was not significantly advantageous over a bolus dose. Additionally, we demonstrated that the affinity-based system was able to improve BMP-2 retention within the scaffold and in vitro activity. However, in vivo implantation of this system demonstrated that only delivery of pre-complexed BMP-2 and heparin resulted in regeneration of bone with mechanical properties not significantly different from intact bone. These results indicate that delivery of BMP-2 and heparin may be an advantageous strategy for clinically challenging bone defects.

Non-healing bone defects have a significant socioeconomic impact in the U.S. with approximately 600,000 bone grafting procedures performed annually. Autografts and allografts are clinically the most common treatments; however, autologous donor bone is in limited supply, and allografts often have poor mechanical properties. Therefore, tissue engineering and regenerative medicine strategies are being developed to address issues with clinical bone grafting. The overall objective of this work was to develop bone tissue engineering strategies that enhance healing of orthotopic defects by targeting specific osteogenic cell signaling pathways. The general approach included the investigation of two different tissue engineering strategies, which both focused on directed osteoblastic differentiation to promote bone formation. In the first cell-based strategy, we hypothesized that constitutive overexpression of the osteoblast-specific transcription factor, Runx2, in bone marrow stromal cells (BMSCs) would promote orthotopic bone formation in vivo. We tested this hypothesis by delivering Runx2-modified BMSCs on synthetic scaffolds to critically-sized defects in rats. We found that Runx2-modified BMSCs significantly increased orthotopic bone formation compared to empty defects, cell-free scaffolds and unmodified BMSCs. This gene therapy approach to bone regeneration provides a mineralizing cell source which has clinical relevance. In the second biomaterial-based strategy, we hypothesized that incorporation of the collagen-mimetic peptide, GFOGER, into synthetic bone scaffolds would promote orthotopic bone formation in vivo without the use of cells or growth factors. We tested this hypothesis by passively adsorbing GFOGER onto poly-caprolactone (PCL) scaffolds and implanting them into critically-sized orthotopic defects in rats. We found that GFOGER-coated scaffolds significantly increased bone formation compared to uncoated scaffolds in a dose dependent manner. Development of this cell-free strategy for bone tissue engineering provides an inexpensive therapeutic alternative to clinical bone defect healing, which could be implemented as a point of care application. Both strategies developed in this work take advantage of specific osteoblastic signaling pathways involved in bone healing. Further development of these tissue engineering strategies for bone regeneration will provide clinically-relevant treatment options for healing large bone defects in humans by employing well-controlled signals to promote bone formation and eliminating the need for donor bone.

Το ερευνητικό πεδίο της παρούσας διδακτορικής διατριβής ήταν η οστεοενσωμάτωση οστικών εμφυτευμάτων. Οι βασικοί στόχοι της έρευνας αφορούσαν την κατανόηση του ρόλου τριών βασικών ρυθμιστικών παραγόντων της διαδικασίας οστεοενσωμάτωσης, δηλαδή της μηχανικής φόρτισης, της επιφανειακής τοπογραφίας και της επιφανειακής (βιο)χημείας, καθώς και τη μελέτη του βασικότερου λόγου αστοχίας των ορθοπεδικών εμφυτευμάτων, της παραγωγής μικροσωματιδίων προϊόντων φθοράς τους. / -

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Thesis--København Tandlægehøjskole. / Summary in Danish. Bibliography: p. 179-194.

Thesis--København Tandlægehøjskole. / Summary in Danish. Bibliography: p. 179-194.

Orientador: Osvaldo Magro Filho / Banca: Wilson Roberto Poi / Banca: Idelmo Rangel Garcia Júnior / Banca: Márcio de Moraes / Banca: Angelo José Pavan / Resumo: Propósito: O objetivo deste estudo foi avaliar histometricamente as alterações ósseas dimensionais, que ocorrem em rebordo atróficos induzidos experimentalmente, com a colocação de implante e enxerto ósseo autógeno ou grânulos de hidroxiapatita/fosfato β-tricálcio (BC) associados à membrana reabsorvível (MR). Materiais e Métodos: Defeitos ósseos foram criados após a extração dos 3 e 4 pré-molares mandibulares de cinco cães beagle. Após 3 meses, foram colocados 2 implantes em cada lado da mandíbula, dentro do rebordo atrófico, resultando em aproximadamente 6mm de superfície exposta do implante. Três grupos de tratamento foram distribuídos aleatoriamente: sem tratamento, MR + Osso autógeno (OA), MR + grânulos de hidroxiapatita/fosfato β-tricálcio. Após 4 meses, os cães foram sacrificados e foi realizada análise histométrica para avaliação de contato osso implante (COI) e ganho ósseo vertical (GOV). As médias de COI e GOV dos três grupos foram comparadas pelo teste de Tukey ao nível de significância de 5%. Resultados: Em 4 meses, o tratamento com MR+OA mostrou COI (%): 26.41 ± 4.90 e GOV (%): 16.06 ± 11.83. O grupo com MR+BC obteve COI (%): 15.16 ± 2.40 e GOV (%): 7.45 ± 9.84 e o grupo A mostrou COI (%): -0.23 ± 0.50 e GOV (%): -1.09 ± 8.99. O grupo MR+OA mostrou regeneração óssea maior (COI e GOV) que o grupo MR+BC e o grupo A (p<0.05). O grupo MR+BC obteve regeneração óssea maior (COI) que o grupo A (p<0.05). Conclusão: Concluiu-se que em rebordos atróficos: (i) tratamento com MR+OA aumenta a regeneração óssea, incluindo ganho ósseo vertical e contato osso implante; (ii) ocorre perda óssea na ausência de técnicas regenerativas / Abstract: Purpose: The objective of this study was to evaluate histometric bone dimensional changes that occur in atrophics defects induced experimentally by placing the implant and autogenous bone graft or hydroxyapatite/β-tricalcium phosphate granules (BC) associated with reabsorbable membrane (RM). Material and Methods: A defect was created after the extraction of three four mandibular premolars of five beagle dogs. After 3 months, 2 implants were placed on each side of the mandible, within the atrophics defects, resulting in approximately 6 mm exposed surface of the implant. Three treatment groups were randomly assigned to: untreated control, RM + autogenous bone, RM + hydroxyapatite /β-tricalcium phosphate granules. After four months, the dogs were sacrificed and histometric analysis was performed to evaluate bone implant contact (BIC) and vertical bone gain (VBG). Mean BIC and VBG in the three groups were compared by Tukey test at a significance level of 5%. Results: In 4 months, treatment with RM + autogenous bone showed BIC (%): 26.41 ± 4.90 and VBG (%): 16.06 ± 11.83. The group RM + BC showed BIC (%): 15.16 ± 2.40 and VBG (%): 7.45 ± 9.84 and the A group obtained BIC (%): -0.23 ± 0.50 and VBG (%): - 1.09 ± 8.99. The RM + autogenous bone group showed greater bone regeneration (BIC and VBG) that RM + BC group and A group (p <0.05). The group received RM + BC greater bone regeneration (BIC) than the A group (p <0.05). Conclusion: We conclude that in atrophics defects: (i) RM + autogenous bone treatment increases bone regeneration, including vertical bone gain and bone implant contact, (ii) bone loss occurs in the absence of regenerative techniques / Doutor

Background. The treatment of patients born with cleft lip and palate has been gradually modified over the years as the surgical procedures have developed and improved. Multidisciplinary team care has evolved and provided improved care with enhanced results. Clefts in the alveolus can be reconstructed by alveolar bone grafting or by periosteoplasty. The main goal is to repair and close the alveolar cleft and create a continuous alveolar processes so that the teeth can erupt. Aims. This thesis has several aims: to investigate the impact of dental status and initial cleft width on the outcome of Secondary alveolar bone grafting (SABG) in patients born with unilateral cleft lip and palate (UCLP) at the 10-year follow-up (Studies I and II); to compare the outcomes of primary periosteoplasty (PPP) with those of SABG in patients born with unilateral cleft lip and alveolus (CLA) (Study III); to evaluate clinical and radiographic conditions and identify factors important for the final treatment outcomes after SABG ( Study IV); to evaluate two radiographic methods, i.e. occlusal radiographs and cone beam tomography (CBCT)) for assessing alveolar bone height ( study IV). Results. In UCLP patients, SABG achieved excellent results in terms of bone height; tended to reduce with time, correlated with dental status and dental restoration factors. Occlusal radiographs correspond well with the CBCT, for evaluating alveolar bone height in cleft area. The width of the initial cleft does not seem to affect the success of SABG. Finally, patients with CLA treated with PPP at the time of lip repair have inferior bone formation outcomes in the cleft area compared with patients treated with SABG at the time of mixed dentition. Conclusion.  Poor dental status and malpositioning negatively affect the long-term survival of bone in the alveolar cleft. The initial cleft width affects certain dental status factors. In adults with UCLP, the alveolar bone height in the cleft was correlated to the presence of gingival inflammation and restorations at 20 years follow-up. Specially designed maintenance therapy is beneficial, after complex dental restorations in the cleft area. SABG is preferred to PPP for the reconstruction of alveolar clefts.