Potencial of different hydroxyapatites as biomaterials in the bone remodeling

Abstract Purpose: To analyze the therapeutic potentials of different hydroxyapatites used for the correction of bone defects in rats. Methods: Forty rats, male, albino wistar, were distributed in 4 groups. They were submitted to a 3.5 mm defect in tibia. They received low purity hydroxyapatite, Strontium hydroxyapatite and hydroxyapatite doped with gallium, having a seven day evaluation time. Histopathology slides were stained with hematoxylin-eosin, for morphological evaluation. Were analyzed inflammatory processes, necrosis, presence of osteoclasts and osteoblasts, presence of the material, presence of white cells, neovascularization and bone neoformation. Results: It was observed that the groups HAPSr and HAPGa, presented better results of trabecular bone, hyaline cartilage and bone marrow more organized. Conclusion: There was improvement in the repair of the bone defect produced, showing that these hydroxyapatites are effective osteoinductive, osteoconductive, osteintegrant agents and have biocompatibility, and may be indicated for use in defect repairs.

Bone repair access of BoneCeramic™ in 5-mm defects: study on rat calvaria

Abstract Objective: The aim of this study was to evaluate the osteoconductive potential of BoneCeramic™ on bone healing in rat calvaria 5-mm defects. Material and Methods: A 5-mm calvaria bone defect was induced in three groups and the defect was not filled with biomaterial [Clot Group (CG)], autogenous bone (AG), or Bone Ceramic Group (BCG). Animals were euthanized after 14 or 28 days and the bone tissue within the central area of the bone defect was evaluated. Results were compared using ANOVA and Tukey test (p<0.05). Immunohistochemistry was performed using primary antibodies against osteocalcin, RUNX-2, TRAP, VEGF proteins, and 3-dimensional images of the defects in μCT were obtained to calculate bone mineral density (BMD). Results: In BCG, the defect was completely filled with biomaterial and new bone formation, which was statistically superior to that in the GC group, at both time-points (p<0.001 for 14 days; p=0.002 for 28 days). TRAP protein showed weak, RUNX-2 showed a greater immunolabeling when compared with other groups, VEGF showed moderate immunostaining, while osteocalcin was present at all time-points analyzed. The μCT images showed filling defect by BCG (BMD= 1337 HU at 28 days). Conclusion: Therefore, the biomaterial tested was found to be favorable to fill bone defects for the reporting period analyzed.

Simvastatin and biphasic calcium phosphate affects bone formation in critical-sized rat calvarial defects

ABSTRACT PURPOSE: To investigate the effects of locally applied simvastatin plus biphasic calcium phosphate (BoneCeramic(r)) or collagen sponge on bone formation in critical-sized bone defects. METHODS: Thirty defects of 5mm in diameter were created bilaterally with a trephine bur in the calvariae of fifteen Wistar rats. The defects were divided into five groups: group 1 - control, no treatment; group 2 (BoneCeramic(r)); group 3 (BoneCeramic(r) + 0.1mg simvastatin); group 4 (collagen sponge); and group 5 (collagen sponge + 0.1mg simvastatin). After eight weeks the animals were euthanized and their calvariae were histologically processed. Hematoxylin and eosin-stained sections were subjected to histological and histomorphometrical analyses. The area of newly formed bone was calculated and compared between groups. RESULTS: The greater amount of a bone-like tissue was formed around the carrier in group 3 (BoneCeramic(r) + 0.1mg simvastatin) followed by group 2 (BoneCeramic(r)), and almost no bone was formed in the other groups. Group 3 was significantly different compared to group 2, and both groups were significantly different compared to the other groups. CONCLUSION: Simvastatin combined with BoneCeramic(r) induced significantly greater amounts of newly formed bone and has great potential for the healing of bone defects.

Histomorphometric evaluation of strontium-containing nanostructured hydroxyapatite as bone substitute in sheep

Abstract The aim of this study is to evaluate the biocompatibility and osteoconductivity in surgical defects of sheep tibias filled with 1% strontium-containing nanostructured hydroxyapatite microspheres (SrHA), stoichiometric hydroxyapatite without strontium microspheres (HA), or blood clots. Santa Ines sheep were subjected to three perforations on the medial side of the left tibia. The biomaterials were characterized by X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) before implantation and by X-Ray Microfluorescence (µFRX) and Scanning Electron Microscopy (SEM) after sheep tibias implantation. Surgical defects were filled with blood clots (control), SrHA (Group 1) or HA (Group 2). After 30 days, 5-µm bone blocks were obtained for histological evaluation, and the blocks obtained from 1 animal were embedded in methylmethacrylate for undecalcified sections. Mononuclear inflammatory infiltrate remained mild in all experimental groups. Giant cells were observed surrounding biomaterials particles of both groups and areas of bone formation were detected in close contact with biomaterials. All groups showed newly formed bone from the periphery to the center of the defects, which the control, HA and SrHA presented 36.4% (± 21.8), 31.2% (± 14.7) and 26.2% (± 12.9) of newly formed bone density, respectively, not presenting statistical differences. In addition, the connective tissue density did not show any significant between groups. The SrHA showing a higher volume density of biomaterial (51.2 ± 14.1) present in the defect compared to HA (32.6 ± 8.5) after 30 days (p = 0.03). Microspheres containing 1% SrHA or HA can be considered biocompatible, have osteoconductive properties and may be useful biomaterials for clinical applications.

Discos de poco espesor de hidroxiapatita cubana sinterizada como sistema de liberacion de fármacos / Cuban low-thickness sintered hydroxyapatite disks as a drug release system

Objetivo: el objetivo principal de este trabajo es estudiar la posibilidad de que sean empleados como sistema de liberación controlada de fármacos, discos de Hidroxiapatita (HA) cubana, fabricados por prensado y sinterizado en hornos eléctrico, sin el empleo de agentes formadores de poros, con porosidades aparentes de 12, 20 y 40 por ciento que fueron dopados por sobre presión con una solución acuosa de alginato de sodio al 5 por ciento y 55 ppm de ceftazidima. Métodos: se estudió la relación entre la penetración del polímero y la porosidad aparente con la liberación del fármaco. Resultados: se demostró que estos discos infiltrados con el polímero que encapsula el fármaco pueden ser utilizados como sistema de liberación controlada. Se demuestra que la porosidad aparente y el tamaño de los poros son influyentes en la penetración del polímero y la masa de fármaco liberado. Conclusiones: En las curvas de liberación obtenidas se observa que los discos pueden ser un potencial material para soportar medicamentos porque se evidencia como el material es capaz de controlar la liberación del medicamento remanente ocluido por un método de dopaje a sobre presión.El perfil indica que en un periodo de siete días se libera controladamente el medicamento

Objective: the main purpose of this study is to examine the potential use of Cuban hydroxyapatite (HA) disks as a controlled drug release system. These disks are manufactured by pressing, and sintered in electric furnaces without using pore-forming agents, with apparent porosities of 12, 20 and 40 percent , and doped by overpressure with a 5 percent sodium alginate aqueous solution and 55 ppm ceftazidime. Methods: a study was conducted of the relationship between penetration of the polymer and apparent porosity with the release of the drug. Results: it was shown that when infiltrated with the polymer encapsulating the drug, these disks may be used as a controlled release system. It was also found that apparent porosity and pore size influence polymer penetration and the mass of drug released. Conclusions: the release curves obtained show that the disks may be a potential drug-supporting material, capable of controlling the release of the remnant drug occluded by an overpressure doping method. The profile reveals that controlled release of the drug is completed in seven days

Comparison of tissue reaction and osteointegration of metal implants between hydroxyapatite/Ti alloy coat: an animal experimental study.

BACKGROUND: One important clinical application of hydroxyapatite (HA) is coating on metal implants to stimulate osteo-integration thus enhancing fixation of the implant to bone, especially plasma-sprayed HA coating applied on Ti alloy substrate. The poor bonding strength between HA and Ti alloy has been of great concern to orthopedists. The biocomptable coat such as Ti alloy (TiO2) coat is one method to improve adhesive strength. OBJECTIVE: The objective of this study was to detect and analyze possible differences in bone formation, bone integration and tissue reaction between group I (uncoated Titanium), group II (Hydroxyapatite coated Titanium), and group III (Hydroxyapatite/TiO2 coated Titanium) implant specimens when embedded into bony hosts. METHOD: Rectangular specimens were implanted into the femoral bone of adult dogs in randomly different sites including: proximal left, proximal right, distal left, distal right. The tailor-made implant specimens were inserted in 5 x 5 mm preprepared sockets. Radiographic evaluation was taken at 0, 1, 3 and 6 months. All animals were sacrificed at 3 and 6 months post implantation. The femoral bone containing implants were dissected and then prepared to be further investigated. The bone-implant interface was analyzed by H&E surface staining, radiography and scanning electron microscopy. Data concerning percentage of osteointegration and adhesiveness of hydroxyapatite layer from different kinds of implants along the entire length of each implants were collected and analyzed for evaluation of any significant differences. RESULTS: No osteo-integration was noted in Group I, but there was 25.57 per cent osteointegration in Group II and 28.63 per cent in Group III. No statistically significant differences were observed between Group II and Group III. However, the coating layer in Group II was found to have detached, in some area, from the metal substrate. Histologically, no adverse tissue reaction was found around any kind of implant. CONCLUSION: Biocompatable bond coat is one of the methods to improve adhesive strength of hydroxyapatite coated implants. In the present study it could be concluded that, besides the improvement in adhesiveness, the intervening TiO2 coating layer had no negative effect concerning bone formation and integration and also showed no adverse surrounding soft tissue reaction.

Resposta do tecido conjuntivo pulpar frente à proteçäo direta com hidróxido de cálcio PA e hodroxiapatita sintética / Response of pulp connective tissue to direct protection with calcium hydroxide and synthetic hydroxyapatite

Foi avaliado o comportamento do tecido pulpar frente à proteçäo direta pelo hidróxido de cálcio P.A. e pela hidroxiapatita sintética em 32 dentes permanentes humanos, obtidos de pacientes com indicaçäo de exodontia por motivos ortodônticos. Transcorridos 60, 90, 120 e 180 dias após a proteçäo pulpar, os dentes foram extraídos, processados, incluídos em parafina, cortados com 5 µm de espessura e corados por H. E. Os resultados demonstraram que a ponte dentinária formada pelo hidróxido de cálcio P.A. apresentou-se mais espessa e organizada nos maiores intervalos de tempo e com reconstituiçäo da camada odontoblástica, ao passo que, para a hidroxiapatita, esse grupo, em todos os intervalos de tempo estudados, exibiu apenas indícios de mineralizaçäo. Portanto, os resultados deste trabalho confirmam que em capeamento pulpar o hidróxido de cálcio P.A. fornece melhores resultados do que a hidroxiapatita sintética

Processo de reparo alveolar em ratos submetidos à ação do complexo osseína-hidroxiapatita. Estudo microscópico / Alveolar repair process in rats submitted to the action of ossein hydroxypatite compound: microscopic study

Ação do complexo osseína-hidroxiapatia (componete do Ossopan 800®) foi avaliada em ratos submetidos a extração dental. O complexo foi administrado aos animais, por via bucal, a partir da cirurgia, e estes foram sacrificados após 3, 7, 15 ou 21 dias. Os resultados mostraram reparação alveolar, com preenchimento ósseo, mineralização e remodelação da crista alveolar, permitindo concluir que o complexo osseína-hidroxiapatita interfere positivamente no processo de reparo alveolar ratos, tanto no aspecto cronológico como também na quantidade e qualidade do novo osso produzido

Análise histopatológica de polpas de pré-molares humanos submetidos a pulpotomia e capeados com hidroxiapatita, hidroxiapatita + glicina e hidróxido de cálcio / Histopatological analysis of human premolar pulps submitted to pulpotomies and caped with hydroxyapatite, hydroxiapatite + glycine and calcium hydroxide

Esta pesquisa foi desenvolvida com o intuito de testar a hidroxiapatita como substância capeadora pulpar em pré-molares humanos submetidos à pulpotomia e comparar com os resultados obtidos com o hidróxido de cálcio. Foram utilizados 24 pré-molares hígidos divididos em 3 grupos de 8 dentes cada. O período de observaçäo foi de 40 dias, após os quais, os dentes foram extraídos, fixados, radiografados e submetidos a avaliaçäo histopatológica das reaçöes pulpares. O grupo I, onde foi utilizado o hidróxido de cálcio + soro fisiológico, apresentou, tanto radiográfica quanto histologicamente, a formaçäo de uma barreira mineralizada e tecido conjuntivo pulpar com características de normalidade. O grupo II e o grupo III, onde foi utilizada a hidroxiapatita + soro fisiológico e a hidroxiapatita + glicina, respectivamente, apresentou como característica principal a difusäo do material para o interior do tecido pulpar, sendo que, no grupo III este fato foi mais intenso. O hidróxido de cálcio continua sendo o material de eleiçäo para pulpotomia em dentes permanentes jovens. A hidroxiapatita näo induziu à formaçäo de tecido mineralizado na maioria dos casos

Estudo histológico em polpas de dentes de humanos submetidas á proteçäo direta com hidróxido de cálcio P.A e hidroxiapatita sintética em pó / Study histologic on teeth tissue pulp after direct protection with calcium hydroxide and sintetic hydroxyapatite

Os autores realizaram análise comparativa do comportamento do tecido pulpar frente á proteçäo direta com hidróxido de cálcio P.A. e hidroxiapatita sintética em pó, considerando o processo inflamatório e a formaçäo de tecido mineralizado em estágios inicial e tardio do processo de reparo. Foram empregados 16 dentes de humanos submetidos á proteçäo direta com as referidas substâncias. Após perído de observaçäo de 02 dias ambas substâncias provocaram necrose pulpa superficial, proliferaçäo colagênica e infiltrado inflamatório discreto; näo sendo evidenciado neoformaçäo mineral. Aos 30 dias observou-se diferença expressiva na reaçäo tissular uma vez que, na maioria das polpas protegidas com hidróxido de cálcio a neoformaçäo mineral foi evidente sobre o tecido exposto, enquanto que nas protegidas com idroxiapatita sintética ocorreu em apenas um caso. O processo inflamatório neste período foi discreto para ambas substâncias

Análise comparativa da biocompatibilidade de materiais cerâmicos diversos em tecido conjuntivo subcutâneo de ratos (Rattus Noovergicus - var. Albinus Rodentia Mammalia) / Comparative analysis of the biocompatibility of various ceramic materials in subcutaneous connective tissue of rats (Rattus Novergicus - var. Albinus Rodentia Mammalia)

Este estudo foi realizado com o objetivo de se comparar as respostas biológicas induzidas por vários materiais implantados no tecido conjuntivo subcutâneo de ratos. Nesta pesquisa, foram implantadas cerâmicas fosfato de cálcio como Interpore-200 (HA), Biopatite (HA) e uma HA fabricada no Depto de Bioquímica da FOB-USP (HA-BIOQ). Também, implantou-se esponja de P.V.C. (como um controle positivo, capaz de induzir reaçäo granulomatosa) e esmalte dental humano, que é composto quase que exclusivamente por HA (98 por cento). O esmalte, em particular, foi utilizado em duas formas: uma particulada, que recebeu o nome de "esmalte granulado", e outra forma em pó, que recebeu o nome de "esmalte pó". Cinquenta animais foram utilizados no experimento, divididos por 5 grupos: Grupo I - 10 animais receberam Interpore-200, Biopatite e HA-BIOQ, e deixados implantados por 30 dias; Grupo II - 10 animais receberam esponja de P.V.C., esmalte granulado e esmalte pó, e deixados por 30 dias; Grupo III - 10 animais receberam Interpore-200, Biopatite e HA-BIOQ e deixados por 60 dias; Grupo IV - 10 animais receberam esponja de P.V.C., esmalte granulado e esmalte pó e deixados por 60 dias; Grupo V - 10 animais receberam Interpore-200, Biopatite e HA-BIOQ e deixados por 12 meses. Após os períodos experimentais, as biópsias colhidas foram processadas histotecnicamente e dois tipos de análises foram realizadas: qualitativa (histopatológico) e quantitativa (volumetria de pontos). Os resultados do exame histopatológico indicaram de modo geral que em 30 dias (Grupos I e II) nenhum material exibia reaçäo inflamatória aguda, embora pudesse ser presenciado alguns resquícios desta reaçäo inicial. Houve a presença de macrófagos e células gigantes de forma discreta à moderada, exceto nos casos de esponja de P.V.C. e do esmalte em pó, onde o quadro foi intenso. Nestes casos houve a formaçäo de uma reaçäo granulomatosa sendo que para o esmalte em pó ocorreu um granuloma tipo imunológico, provavelmente pela existência de material orgânico nas partículas e pela maior área de contato destas com o tecido conjuntivo subcutâneo. A fibrose foi muito discreta, assim como a presença de linfócitos e a reaçäo vascular. Com 60 dias (Grupos III e IV) o infiltrado inflamatório de modo geral regrediu, exceto para os casos de esponja de P.V.C. e esmalte em pó. A Biopatite também apresentou grande quantidade de macrófagos e células gigantes em comparaçäo com o Interpore-200 e a HA-BIOQ...