Reparação óssea em alvéolos de ratas ovarectomizadas após implante com biovidro: análise histomorfométrica e imunoistoquímica

Pós-graduação em Odontologia - FOA

Regeneração óssea guiada com o uso de membrana de copolímero PLA/PGA em levantamento da membrana do seio maxilar: estudo experimental com análises histomorfométrica e imunoistoquímica

Pós-graduação em Odontologia - FOA

Cimentos bioativos injetáveis funcionalizados com peptídeo osteogênico para reparação óssea

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo inicial da degradação in vivo de poli(L-co-D,L ácido lático), sintetizado em laboratório, aplicado como prótese tibial em coelhos

The copolymer poly (L-co-D,L lactic acid), PLDLA, has gained prominence in the field of temporary prostheses due to the fact that their time of degradation is quite compatible with the requirement in the case of osseous fracture. In this work the in vivo degradation of devices from copolymer, as a system of plates and screws, used in fixation of the tibia of rabbits was studied. The devices were implanted in 15 adult rabbits, albinos, New Zealand race, and they were used as control devices of alloys of titanium (Ti-6Al-4V/ V grade). The use of copolymers, synthesized in the laboratory, was tested in the repair of fracture in rabbits'tibias, being assessed in the following times: 2 weeks, 2 months and 3 months. Morphological analysis of tissue surrounding the plate and screw system, for 2 weeks of implantation, showed the presence of osteoblasts, indicating a pre bone formation. After 2 months there was new bone formation in the region in contact with the polymer. This bone growth occurred simultaneously with the process of PLDLA degradation, invading the region where there was polymer and after 3 months there was an intense degradation of the copolymer and hence greater tissue invasion compared to 2 months which characterized bone formation in a region where the polymer degraded. The in vivo degradation study of the devices for PLDLA by means of histological evaluations during the period of consolidation of the fracture showed the efficiency of plate and screw system, and it was possible to check formation of bone tissue at the implantation site, without the presence of inflammatory reaction

Bone response to biosilicates® with different crystal phases

The aim of this study was to investigate the histological and histomorphometrical bone response to three Biosilicates with different crystal phases comparing them to Bioglass®45S5 implants used as control. Ceramic glass Biosilicate and Bioglass®45S5 implants were bilaterally inserted in rabbit femurs and harvested after 8 and 12 weeks. Histological examination did not revealed persistent inflammation or foreign body reaction at implantation sites. Bone and a layer of soft tissue were observed in close contact with the implant surfaces in the medullary canal. The connective tissue presented few elongated cells and collagen fibers located parallel to implant surface. Cortical portion after 8 weeks was the only area that demonstrated significant difference between all tested materials, with Biosilicate 1F and Biosilicate 2F presenting higher bone formation than Bioglass®45S5 and Biosilicate® vitreo (p=0.02). All other areas and periods were statistically non-significant (p>0.05). In conclusion, all tested materials were considered biocompatible, demonstrating surface bone formation and a satisfactory behavior at biological environment.

Enhanced bone apposition to Brazilian microrough titanium surfaces

It has recently been reported that machined and microrough (micro) Brazilian titanium (Ti) implants have good production standards. The aim of this study was to evaluate in vivo bone formation around 2 different implant surfaces placed in dog's mandible. Thirty-two screw-typed Ti implants were used in this study. Mandibular premolars were extracted in 8 dogs and, after 12 weeks, 2 machined (Neodent Titamax, Brazil) and 2 micro implants (Neodent Titamax Porous, Brazil) were placed in each animal. Biopsies were taken at 3 and 8 weeks post-implantation and stained with Stevenel's blue and Alizarin red for histomorphometric measurements of bone-to-implant contact (BIC), bone area between threads (BABT) and bone area within the mirror area (BAMA). Data were analyzed statistically by two-way ANOVA (α=0.05). While at 3 weeks micro implants exhibited significantly more BIC than machined ones (55 ± 12.5% and 35.6 ± 15%, p<0.05), no significant difference in such parameter was detected at 8 weeks (51.2 ± 21% and 48.6 ± 18.1%, p>0.05). There were no significant differences in BABT and BAMA between the implants. Micro surfaces promoted higher contact osteogenesis. These data indicate that this commercial micro Ti implant surface enhances contact osteogenesis at an early post-implantation period when compared to the machined one.

Bone response to a Ca- and P-enriched titanium surface obtained by anodization

This study evaluated bone response to a Ca- and P- enriched titanium (Ti) surface treated by a multiphase anodic spark deposition coating (BSP-AK). Two mongrel dogs received bilateral implantation of 3 Ti cylinders (4.1 x 12 mm) in the humerus, being either BSP-AK treated or untreated (machined - control). At 8 weeks postimplantation, bone fragments containing the implants were harvested and processed for histologic and histomorphometric analyses. Bone formation was observed in cortical area and towards the medullary canal associated to approximately 1/3 of implant extension. In most cases, in the medullary area, collagen fiber bundles were detected adjacent and oriented parallel to Ti surfaces. Such connective tissue formation exhibited focal areas of mineralized matrix lined by active osteoblasts. The mean percentages of bone-to-implant contact were 2.3 (0.0-7.2 range) for BSP-AK and 0.4 (0.0-1.3 range) for control. Although the Mann-Whitney test did not detect statistically significant differences between groups, these results indicate a trend of BSP-AK treated surfaces to support contact osteogenesis in an experimental model that produces low bone-to-implant contact values.

Repair of critical-size defects with autogenous periosteum-derived cells combined with bovine anorganic apatite/collagen: an experimental study in rat calvaria

The aim of this study was to evaluate the bone repair using autogenous periosteum-derived cells (PDC) and bovine anorganic apatite and collagen (HA-COL). PDC from Wistar rats (n=10) were seeded on HA-COL discs and subjected to osteoinduction during 6 days. Critical-size defects in rat calvarias were treated with blood clot (G1), autogenous bone (G2), HA-COL (G3) and HA-COL combined with PDC (G4) (n=40), and then analyzed 1 and 3 months after surgeries. Radiographic analysis exhibited no significant temporal change. G1 and G2 had discrete new marginal bone, but the radiopacity of graft materials in G2, G3 and G4 impaired the detection of osteogenesis. At 3 months, histopathological analysis showed the presence of ossification islets in G1, which was more evident in G2, homogeneous new bone around HA-COL in G3 and heterogeneous new bone around HA-COL in G4 in addition to moderate presence of foreign body cells in G3 and G4. Histomorphometric analysis showed no change in the volume density of xenograft (p>0.05) and bone volume density in G2 was twice greater than in G1 and G4 after 3 months (p<0.05), but similar to G3. The PDC did not increase bone formation in vivo, although the biomaterial alone showed biocompatibility and osteoconduction capacity.

Histological and radiological changes in cranial bone in the presence of bone wax

PURPOSE: To quantify the amount of bone formation in the calvarial region of Wistar rats after craniotomy using bone wax as a haemostatic agent. METHODS: Surgery to produce bilateral, symmetric, full-thickness cranial defects (area: 18 mm²) was performed in eight animals. The right side of the cranium remained open and the edges of the left side osseous defect was covered with bone wax. Calvaria were imaged immediately after surgery and 12 weeks postoperatively by computerized tomography. The areas of the bone defects were measured in three-dimensional images using Magics 13.0 (Materialise-Belgic, software CAD). RESULTS: The average amount of bone formation on the left and right side respectively was 4.85 mm² and 8.16 mm². Statistically significant differences between the amount of bone formation on the left and right sides were seen. CONCLUSIONS: Bone wax significantly diminishes the rate of bone formation in calvarial defects in a rat model.

Alveolar osseous defect in rat for cell therapy: preliminary report

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm² of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 ± 1.31 mm² and the average area of alveolar defect at time point of 4 weeks was 9.03 ± 1.17 mm². The average amount of bone formation at time point of 2 weeks was 5.73 ± 1.31 mm² and the average amount of bone formation at time point of 4 weeks was 19 ± 1.17 mm². Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

Tratamentos não farmacológicos na estimulação da osteogênese

A carga mecânica provoca microdeformações ósseas, que estimulam células osteoblásticas e, conseqüentemente, promovem adaptações nos ossos, muitas vezes relacionadas com uma menor reabsorção óssea e um aumento na formação óssea local. No entanto, o estímulo para formação óssea depende do número e freqüência das deformações aplicadas no osso. Concomitantemente aos estímulos ósseos providos pelas cargas mecânicas, é importante uma dieta rica em cálcio, a qual também beneficia o aumento da massa óssea. Entretanto, existem também outros métodos não farmacológicos, como o ultra-som pulsado de baixa intensidade, a estimulação elétrica e o laser, que já mostraram efeitos positivos na promoção da osteogênese. Assim, realizou-se um levantamento na literatura, no período de 1982 a 2001, sobre esses métodos não farmacológicos com o objetivo de avaliar tais métodos alternativos, que ajudam no aumento da massa óssea ou no estímulo à osteogênese.

The influence of menopausal status on bone turnover and disease control in breast cancer patients with metastatic bone disease treated with chemotherapy plus zoledronic acid : an exploratory retrospective cohort study

RESUMO: Introdução: Uma meta-análise recente demonstrou que uso adjuvante de ácido zoledrónico (AZ) em mulheres pós-menopáusicas com cancro da mama precoce (CM) conduz a redução do risco de morte por CM em 17%. Investigámos o efeito do estado hormonal (pré [PrM] vs pós-menopausa tardia [PoM]) na remodelação óssea e controlo de doença em mulheres com CM e metástases ósseas (MO) tratadas com AZ e quimioterapia (QT). Métodos: Neste estudo de coorte retrospetivo, colhemos variáveis clinico-patológicas e quantificámos o telopéptido N-terminal (NTX) urinário e marcadores tumorais (MT) séricos em mulheres com CM e MO tratadas com QT e AZ. As doentes foram divididas em PrM (<45 anos) e PoM (>60 anos). Endpoints do estudo: variação do NTX, CA15.3 e CEA nos meses 3, 6 e 9, tempo até falência de QT de primeira-linha e sobrevivência. Quando apropriado foram usados os testes de Wilcoxon rank-sum, modelo de efeitos lineares mistos, teste log-rank e modelo de Cox. Resultados: Quarenta doentes foram elegíveis para análise (8 PrM e 32 PoM). Depois da introdução de AZ e QT, os níveis de NTX e MT caíram no coorte global. O perfil de resposta não diferiu entre grupos no mês 3 ou em tempos posteriores (valor-p para interação tempo-estado hormonal no mês 3=0.957). Ademais, o perfil de resposta dos MT também não diferiu entre grupos. O tempo mediano até falência de primeira-linha de QT em PrM e PoM foi de 15.2 e 17.4 meses, respetivamente. Não foi identificada diferença significativa entre grupos, quer em análise univariada quer após controlo para envolvimento visceral (p=0.399 e 0.469, respetivamente). Igualmente, não houve diferenças em termos de sobrevivência. Conclusões: Neste coorte, não foram identificadas diferenças no controlo de NTX ou MT em função do estado menopausico. Igualmente, não foi identificada diferença no tempo até falência de primeira-linha de CT ou sobrevivência.----------- ABSTRACT: Background: A recent meta-analysis showed that the adjuvant use of zoledronic acid (ZA) in postmenopausal women with early breast cancer (BC) leads to a reduction in the risk of breast cancer death by 17%. We investigated the effect of the hormonal status (pre [PrM] vs late post menopause [PoM]) on bone turnover and disease control among women with BC and boné metastases (BM) treated with ZA and chemotherapy (CT). Methods: In this retrospective cohort study, we collected clinicopathologic variables, urinary Nterminal telopeptide (NTX) and serum tumor marker levels from women with BC and BM treated with CT and ZA. Patients were divided in PrM (<45 years) and PoM (>60 years). Study endpoints were NTX, CA15.3 and CEA variation at 3, 6 and 9 months, and time to first-line CT failure and survival. We performed multilevel mixed-effects linear regression models to assess the variation of repeated measures and cox regression models for time to event outcomes. Results: Forty patients were eligible for analysis (8 PrM and 32 PoM). After introduction of ZA and CT, NTX and tumor markers declined in the overall cohort. Response profile was similar between menopausal groups at month 3 and at later time points (p-value for time-hormonal status interaction at month 3=0.957). Furthermore, tumor markers response profile was also equal between groups. Median time to first-line CT failure in PrM and PoM women was 15.2 and 17.4 months, respectively. No significant difference between groups was found, either using a univariate analysis or after controlling for visceral disease involvement (p=0.399 and 0.469, respectively). Likewise, no differences in survival were found. Conclusions: In this cohort, no differences were found in terms of NTX or tumor markers control according to menopausal status. Similarly, no difference in time to first-line CT failure or survival was found.

Processamento e caracterização de compósitos de Ti-HAP para aplicações biomédicas

Dissertação de mestrado integrado em Engenharia de Materiais

Análise por tomografia computadorizada do enxerto autógeno na cirurgia de "sinus lift"

OBJETIVO: Quantificar a formação óssea nos enxertos com e sem plasma rico em plaquetas, obtido pelos métodos de centrifugação e aférese, comparando os três tipos de enxertos realizados por meio de análise tomográfica. MATERIAIS E MÉTODOS: Este estudo prospectivo, duplo cego, utilizou uma amostra composta de 34 pacientes adultos, de ambos os sexos, com idade média de 48 anos e 8 meses, portadores de pneumatização unilateral ou bilateral dos seios maxilares, que necessitavam de enxertos ósseos, com a finalidade de melhorar as condições locais para a colocação dos implantes dentários. Todos os pacientes realizaram tomografia computadorizada antes da cirurgia. Foram operados 53 seios maxilares, divididos em três grupos: enxerto de plasma rico em plaquetas obtido pelos métodos de aférese, centrifugação e enxerto apenas de osso autógeno. Após seis meses do procedimento cirúrgico foram realizados novos exames de imagem. RESULTADOS: Pela avaliação tomográfica, houve crescimento em altura e em largura nos três grupos quando foram comparados os momentos inicial e final, entretanto, não houve diferença estatística para a altura e para a largura. CONCLUSÃO: Evidências clínicas demonstram a eficácia dos enxertos autógenos, principalmente os associados a fatores indutores de crescimento ósseo, como o plasma rico em plaquetas, recuperando o arcabouço maxilofacial, necessário para a reconstrução protética e funcional por meio de implantes dentários.

Osteoporose em caprinos

Foi realizado um estudo de casos de osteoporose em caprinos provenientes de uma propriedade na área de abrangência do LPV-UFSM, determinando a epidemiologia, o quadro clínico-patológico e discutindo os prováveis mecanismos patogenéticos. Cinco cabras, fêmeas, SRD, de seis meses a seis anos de idade foram afetadas. As cabras eram mantidas em campo nativo, sem suplementação com ração e sob superlotação. Os principais sinais clínicos foram emagrecimento, dificuldade de locomoção e permanência em decúbito por longos períodos. As principais alterações macroscópicas nos ossos examinados foram vistas nas superfícies de corte e caracterizavam-se por depleção do osso esponjoso (porosidade) e redução acentuada da espessura do osso cortical. Havia também marcada atrofia serosa da gordura da medula óssea. Microscopicamente, nas regiões avaliadas (úmero proximal, rádio distal, fêmur distal, tíbia proximal e corpos das vértebras lombares) foi observada redução moderada a acentuada do número e da espessura das trabéculas ósseas nas epífises e metáfises dos ossos longos e nos corpos vertebrais. Os achados clínico-patológicos indicaram que a osteoporose observada provavelmente foi causada pela desnutrição. As alterações ósseas (diminuição no número e na espessura das trabéculas do osso esponjoso) sugerem que ambos os mecanismos, má formação óssea e reabsorção óssea aumentada, contribuíram para a ocorrência de osteoporose nos caprinos deste estudo.