Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo / Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model.

AIM: To compare the in vivo bone formation capacity of of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxiapatite and the other one on bioactive mesoporous glass. MATERIALS AND METHODS: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite scaffold, and with bioactive mesoporous glass scaffold. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. RESULTS: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than the autograft group. CONCLUSION: Both scaffolds seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model. / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo.

AIM: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. MATERIALS AND METHODS: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. RESULTS: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. CONCLUSION: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

The Influence of the Matrix on the Apatite-Forming Ability of Calcium Containing Polydimethylsiloxane-Based Cements for Endodontics.

This study aimed to characterize the chemical properties and bioactivity of an endodontic sealer (GuttaFlow Bioseal) based on polydimethylsiloxane (PDMS) and containing a calcium bioglass as a doping agent. Commercial PDMS-based cement free from calcium bioglass (GuttaFlow 2 and RoekoSeal) were characterized for comparison as well as GuttaFlow 2 doped with dicalcium phosphate dihydrate, hydroxyapatite, or a tricalcium silicate-based cement. IR and Raman analyses were performed on fresh materials as well as after aging tests in Hank's Balanced Salt Solution (28 d, 37 °C). Under these conditions, the strengthening of the 970 cm−1 Raman band and the appearance of the IR components at 1455−1414, 1015, 868, and 600−559 cm−1 revealed the deposition of B-type carbonated apatite. The Raman I970/I638 and IR A1010/A1258 ratios (markers of apatite-forming ability) showed that bioactivity decreased along with the series: GuttaFlow Bioseal > GuttaFlow 2 > RoekoSeal. The PDMS matrix played a relevant role in bioactivity; in GuttaFlow 2, the crosslinking degree was favorable for Ca2+ adsorption/complexation and the formation of a thin calcium phosphate layer. In the less crosslinked RoekoSeal, such processes did not occur. The doped cements showed bioactivity higher than GuttaFlow 2, suggesting that the particles of the mineralizing agents are spontaneously exposed on the cement surface, although the hydrophobicity of the PDMS matrix slowed down apatite deposition. Relevant properties in the endodontic practice (i.e., setting time, radiopacity, apatite-forming ability) were related to material composition and the crosslinking degree.

Effectiveness of Calcium Phosphate Desensitising Agents in Dental Hypersensitivity Over 24 Weeks of Clinical Evaluation.

BACKGROUND: Calcium phosphate-based compounds are used to treat dental hypersensitivity (DH). Their long-term clinical behaviour needs further research. This study compared the 24-week effectiveness of Teethmate Desensitizer (TD), a pure tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) powder/water, to that of Dentin Desensitizer (DD), and Bite & White ExSense (BWE), both of calcium phosphate crystallites. METHODS: A total of 105 subjects were selected. A random table was utilised to form three groups of 35 subjects. DH was evaluated using the evaporative sensitivity, tactile sensitivity tests, and the visual analogue scale (VAS) of pain. Response was recorded before the application of the materials (Pre-1), immediately after (Post-0), at 1 week (Post-1), 4 weeks (Post-2), 12 weeks (Post-3) and 24 weeks (Post-4). The non-parametric distribution was assessed with the Shapiro-Wilk statistical test. Intra-group differences for the six time points were evaluated with the Friedman statistical test and the Kruskal-Wallis test. RESULTS: All the materials decreased DH after 24 weeks in comparison to Pre-1. However, the TTCP/DCPD cement showed the greatest statistical efficiency. CONCLUSIONS: The significant decrease of VAS scores produced by TD in the long term suggest the material as the most reliable in the clinical relief of DH.

Impact of crystallinity and crystal size of nanostructured carbonated hydroxyapatite on pre-osteoblast in vitro biocompatibility.

Nanostructured carbonated hydroxyapatite (nCHA) is a promising biomaterial for bone tissue engineering due to its chemical properties, similar to those of the bone mineral phase and its enhanced in vivo bioresorption. However, the biological effects of nCHA nanoparticles on cells and tissues are not sufficiently known. This study assessed the impact of exposing pre-osteoblasts to suspensions with high doses of nCHA nanoparticles with high or low crystallinity. MC3T3-E1 pre-osteoblasts were cultured for 1 or 7 days in a culture medium previously exposed to CHA nanoparticles for 1 day. Control groups were produced by centrifugation for removal of bigger nCHA aggregates before exposure. Interaction of nanoparticles with the culture medium drastically changed medium composition, promoting Ca, P, and protein adsorption. Transmission Electron microscopy revealed that exposed cells were able to internalize both materials, which seemed concentrated inside endosomes. No cytotoxicity was observed for both materials, regardless of centrifugation, and the exposure did not induce alterations in the release of pro-and anti-inflammatory cytokines. Morphological analysis revealed strong interactions of nCHA aggregates with cell surfaces, however without marked alterations in morphological features and cytoskeleton ultrastructure. The overall in vitro biocompatibility of nCHA materials, regardless of physicochemical characteristics such as crystallinity, encourages further studies on their clinical applications.

Proximal Femoral Bone Regeneration After an Uncemented Hydroxyapatite-coated Long-stem in Revision Hip Surgery.

BACKGROUND: Bone remodelling with lateral femoral cortex thinning is a major concern after extensively porous-coated long-stem in revision surgery. Extensive hydroxyapatite coated long-stems were introduced to improve osseointegration, but bone remodelling changes have not been quantified. OBJECTIVE: The question of whether bone remodelling changes from extensive hydroxyapatite-coated long stems influence the durability of femoral revision, clinical outcome is assessed in follow-up radiographs. METHODS: Uncemented straight monoblock hydroxyapatite-coated long-stems used in revision hip surgery for aseptic loosening were assessed in a consecutive series of 64 hips (60 patients). Mean follow-up was 8.6 years and the mean age at surgery was 70 years (27-91). The pre-operative bone defect was classified according to Paprosky. Cortical struts were not used in this series. Cortical index and femoral cortical width were measured at three different levels at different periods. RESULTS: Four patients with pain under level 4 due to stem loosening needed an exchange surgery of their femoral component, but two patients rejected re-surgery. The cumulative probability of not having aseptic loosening was 91.2% (95% confidence interval 73.5-96.9) at 10 years according to Kaplan and Meier. Twenty-seven of 35 osteolytic lesions had disappeared or decreased at the last follow-up. The thickness of the lateral and medial cortex increased over the course of the study at different levels. Increases of femoral cortex thickness were greater in men and in cases with mild bone defects. CONCLUSION: Although clinical outcome of the hydroxyapatite-coated long stem in revision surgery is good but not outstanding, most osteolytic lesions heal and the femoral cortex thickness increases at different levels.

Hydroxyapatite-ciprofloxacin delivery system: Synthesis, characterisation and antibacterial activity.

The main objective of this study was to synthesize hydroxyapatite-ciprofloxacin composites using a chemical precipitation method and to evaluate the properties and in vitro release profile of the drug from the hydroxyapatite-ciprofloxacin composites. Composite characterization was achieved by FT-IR, XRD and DLS. Ciprofloxacin determination was accomplished by HPLC, resulting in good incorporation efficiency of the drug (18.13 %). The in vitro release study (Higuchi model C = K t1/2 and Ritger-Peppas model, C = K t0.6) showed a diffusion-controlled mechanism. The antibacterial activity showed that the bacterial growth inhibition zones were approximately equal for the synthesis composites and for the mechanical mixture on the Staphylococcus aureus germ. The use of hydroxyapatite, which is a biocompatible, bioactive and osteoconductive material, with ciprofloxacin, which has good antibacterial activity in this composite, makes it suitable for the development of bone grafts. Furthermore, the synthesis process allows a slow local release of the drug.

New concept of 3D printed bone clip (polylactic acid/hydroxyapatite/silk composite) for internal fixation of bone fractures.

Open reduction with internal fixation is commonly used for the treatment of bone fractures. However, postoperative infection associated with internal fixation devices (intramedullary nails, plates, and screws) remains a significant complication, and it is technically difficult to fix multiple fragmented bony fractures using internal fixation devices. In addition, drilling in the bone to install devices can lead to secondary fracture, bone necrosis associated with postoperative infection. In this study, we developed bone clip type internal fixation device using three- dimensional (3D) printing technology. Standard 3D model of the bone clip was generated based on computed tomography (CT) scan of the femur in the rat. Polylacticacid (PLA), hydroxyapatite (HA), and silk were used for bone clip material. The purpose of this study was to characterize 3D printed PLA, PLA/HA, and PLA/HA/Silk composite bone clip and evaluate the feasibility of these bone clips as an internal fixation device. Based on the results, PLA/HA/Silk composite bone clip showed similar mechanical property, and superior biocompatibility compared to other types of the bone clip. PLA/HA/Silk composite bone clip demonstrated excellent alignment of the bony segments across the femur fracture site with well-positioned bone clip in an animal study. Our 3D printed bone clips have several advantages: (1) relatively noninvasive (drilling in the bone is not necessary), (2) patient-specific design (3) mechanically stable device, and (4) it provides high biocompatibility. Therefore, we suggest that our 3D printed PLA/HA/Silk composite bone clip is a possible internal fixation device.

[Mineral composition of mixed saliva in patients with dental fluorosis]. / Mineral'nyi sostav smeshannoi sliuny u patsientov s fliuorozom zubov.

The aim of the study was to assess the mineral composition of mixed saliva in dental fluorosis patients undergoing treatment with microabrasion and bleaching. The study included 60 patients aged 18-35 years with various forms of dental fluorosis. Group 1 included 40 patients in which enamel microabrasion was performed, group 2 - 20 patients with microabrasion and bleaching. Mixed saliva composition was analyzed with Olimpus automatic analyzing device. Dental fluorosis treatment in both groups resulted in saliva mineral composition changed associated with enamel demineralization which proves the necessity for calcium and phosphate containing compositions in these treatment groups.

O gálio e a patologia óssea / Gallium and bone pathology

PROPOSTA: Revisão de trabalhos científicos referentes à incorporação do gálio no tecido ósseo, ao mecanismo da atividade terapêutica desse elemento, bem como a formação, crescimento e solubilidade da hidroxiapatita na presença dos sais de gálio. JUSTIFICATIVA: Diferente de outras drogas que impedem a perda de cálcio, os sais de elemento traço gálio são eficazes em hipercalcemia severa. O gálio (geralmente na forma de nitrato) aumenta a concentração de cálcio e fósforo no osso, influindo nos osteoclastos de maneira direta não tóxica, em doses surpreendentemente baixas. Apesar de que os detalhes do mecanismo de ação do gálio não são bem esclarecidos, está comprovado que esse mecanismo envolve a inserção do gálio na matriz de hidroxiapatita, protegendo-a contra a reabsorção e melhorando as propriedades biomecânicas do sistema esquelético. Este fármaco age também nos componentes celulares do osso, impedindo sua absorção ao diminuir a secreção ácida dos osteoclastos. São necessárias mais publicações sobre o uso do gálio no tratamento de várias doenças onde prevalece esta patologia. CONCLUSÕES: Devido as suas características interessantes e promissoras, o gálio merece ser futuramente avaliado do ponto de vista experimental e clínico, como um agente antiabsortivo em ortopedia, traumatologia e doenças relacionadas com o câncer. Maior conhecimento dos mecanismos envolvidos pode fornecer as idéias para estratégia terapêutica, com o objetivo de diminuir hipercalcemia e perda óssea. Espera-se que novos compostos do gálio sejam desenvolvidos e avaliados clinicamente.

PURPOSE: To review the literature concerning the incorporation of gallium into bone tissue, mechanisms of therapeutic activity of this element, as well as the formation, growth and solubility of hydroxiapatite in the presence of gallium salts. JUSTIFICATION: In contrast to other calcium-saving drugs, salts of trace element gallium are effective in severe hypercalcemias. Gallium (most commonly in the form of its nitrate) enhances calcium and phosphorus content of the bone and has direct, noncytotoxic effects on osteoclasts at markedly low doses. Although the details of gallium action on the bone are still uncertain, it is well established that the mechanism involves gallium insertion into the hydroxiapatite matrix protecting it from resorbtion and improving biomechanical properties of the skeletal system. The drug also acts on the cellular components of bone to reduce bone resorbtion by decreasing acid secretion by osteoclasts. More has to be published about the use of gallium in managing a series of clinical conditions in which this pathology is pronounced. CONCLUSIONS: Due to its interesting and promising profile gallium merits further experimental and clinical evaluation as an antiresorbtive agent in orthopaedics, traumatology and cancer-related conditions. Greater knowledge of the mechanisms involved may provide insights for therapeutic strategies aimed at diminishing hypercalcemy and bone loss. New gallium compounds are expected to be developed and tested clinically.

Utilização de Biogran e Calcitite em defeitos ósseos. Estudo histológico em macacos Cebus apella / Utilization of Biogran and Calcitite in bone defects. Hystologic study in monkeys Cebus apella

A proposição deste trabalho foi avaliar e comparar histologicamente a efetividade do Biogran e Calcitite no preenchimento de cavidades ósseas cirurgicamente criadas, em mandíbulas de quatro macacos adultos jovens Cebus apella. Foram realizadas cirurgicamente três cavidades transfixantes de 5 mm de diâmetro na região de ângulo da mandíbula sendo duas cavidades no lado direito e uma no lado esquerdo. Os defeitos ósseos foram divididos em três grupos de acordo com o material utilizado, sendo: D1 preenchido com biovidro (Biogran); D2, sem preenchimento; e E, preenchido com hidroxiapatita (Calcitite). Após o período de 180 dias os animais foram sacrificados, as peças removidas e processadas para obtenção de cortes histológicos. Após análise histológica descritiva os resultados demonstraram que não ocorreu formação óssea no grupo D2, o material Biogran permitiu neoformação óssea com reparação total do defeito criado sendo este quase totalmente reabsorvido e substituído por tecido ósseo e os poucos cristais restantes do material encontravam-se em íntimo contato com tecido ósseo neoformado. O material Calcitite não permitiu neoformação óssea sendo que os grânulos do material presentes no interior da cavidade apresentaram-se envoltos por tecido conjuntivo fibroso. Baseados nos resultados obtidos podemos concluir que: apenas o biovidro propiciou a obliteração das cavidades por tecido ósseo e que a hidroxiapatita se apresentou, em grande quantidade, envolta por tecido fibroso e ausência de formação óssea

The present study compares the biological behavior of Biogran and Calcitite as fillers of surgical cavities in the mandible of four adult monkeys (Cebus apella). The surgical cavities were prepared through both mandibular cortices, with a diameter of 5 mm, in the angle region. Two cavities were prepared in the right side and one in the left, divided into groups, according to the material employed as follows: 1 - D1 filled with bio-glass (BioGran), 2 - D2 without bio-filling, 3 - E filled with hidroxyapatite (Calcitite). After 180 days the animals were sacrificed and the specimens removed for histological processing. Results showed no bone formation in group D2 (empty cavities). Biogran allowed bone formation and total repair of the bone defect. It was almost totally resorbed and substitued by bone. The few remaining crystals were in intimate contact with newly formed bone. Calcitit did not allow bone formation and granules inside the cavities were involved by connective tissue. Based upon those results, conclusions were: 1) Bio-glass resulted in total obliteration of the surgical cavity with bone; 2) Hydroxyapatite was present in large amount and involved by connective tissue, without newly formed bone