Research progress on surface modification of titanium implants by strontium ions / 口腔疾病防治

@#Traditional titanium implants do not completely meet the clinical requirements because they are bioinert. The surface of titanium implants, modified by strontium ions, can enhance osseointegration and reduce peri-implantitis. In this paper, the biological properties of titanium implant surfaces modified by strontium ions were reviewed. Strontium ions can be coated on the implant surface by hydrothermal treatment, electrochemical deposition, phosphate chemical conversion, flame-spraying, supramolecular self-assembly, magnetron sputtering, laser deposition and alkali etching. Implant surfaces modified by strontium ions can not only promote osteogenesis and early osseointegration but also inhibit bacterial growth and reduce postoperative infections. Even better osseointegration and antibacterial effects can be achieved when strontium ions are incorporated with other elements, such as silver, zinc, gallium, and calcium. However, most of the studies on the use of strontium ion-modified titanium implants are animal experiments and in vitro experiments, and the observation time is short compared with the actual service life of the implants. Thus, the conclusions obtained may be different from the actual clinical application, and the long-term effects need to be studied. In addition, the osteogenic effects of various modification methods also need to be compared. Future research can focus on the following points: ① to find efficient modification methods that can be widely used in the clinic; ②to study how to control the concentration of strontium ions near the implant to exert their biological function and reduce their toxic side effects; and ③ to conduct long-term follow-up clinical trials to observe their osteogenic and antibacterial effects.

Effect of pH on the chelation between strontium ions and decellularized small intestinal submucosal sponge scaffolds / 北京大学学报(医学版)

OBJECTIVE@#To investigate the preparation of decellularized small intestinal submucosa (dSIS) sponge scaffolds with chelated strontium (Sr) ions at different pH values, and to select the appropriate pH values for synthesizing Sr/dSIS scaffolds using the physicochemical properties and biocompatibility of the scaffolds as evaluation indexes.@*METHODS@#(1) Sr/dSIS scaffolds preparation and grouping: After mixing dSIS solution and strontium chloride solution in equal volumes, adjusting pH of the solution to 3, 5, 7, and 9 respectively, porous scaffolds were prepared by freeze-drying method after full reaction at 37℃, which were named Sr/dSIS-3, -5, -7, and -9 respectively, and the dSIS scaffolds were used as the control group. (2) Physicochemical property evaluation: The bulk morphology of the scaffolds was observed in each group, the microscopic morphology analyzed by scanning electron microscopy, and the porosity and pore size determined, the surface elements analyzed by energy spectroscopy, the structure of functional groups analyzed by infrared spectroscopy, the chelation rate determined by atomic spectrophotometry, the water absorption rate detected by using specific gravity method, and the compression strength evaluated by universal mechanical testing machine.(3) Biocompatibility evaluation: The cytotoxicity and proliferative effect to bone mesenchymal stem cells (BMSCs) of each group were evaluated by Calcein-AM/PI double staining method.@*RESULTS@#Scanning electron microscopy showed that the scaffolds of each group had an interconnected three-dimensional porous structure with no statistical difference in pore size and porosity. Energy spectrum analysis showed that strontium could be detected in Sr/dSIS-5, -7 and -9 groups, and strontium was uniformly distributed in the scaffolds. Functional group analysis further supported the formation of chelates in the Sr/dSIS-5, -7 and -9 groups. Chelation rate analysis showed that the Sr/dSIS-7 group had the highest strontium chelation rate, which was statistically different from the other groups (P < 0.05). The scaffolds in all the groups had good water absorption. The scaffolds in Sr/dSIS-5, -7 and -9 groups showed significantly improved mechanical properties compared with the control group (P < 0.05). The scaffolds in all the groups had good biocompatibility, and the Sr/dSIS-7 group showed the best proliferation of BMSCs.@*CONCLUSION@#When pH was 7, the Sr/dSIS scaffolds showed the highest strontium chelation rate and the best proliferation effect of BMSCs, which was the ideal pH value for the preparation of the Sr/dSIS scaffolds.

Enfoques terapéuticos de la osteoporosis / Therapeutic approaches to osteoporosis

La finalidad del tratamiento de la osteoporosis es la prevención primaria y secundaria de fracturas. Las indicaciones para las intervenciones terapéuticas en la osteoporosis deben derivarse de la determinación del riesgo absoluto de fractura, que tiene en cuenta la evaluación de los factores de riesgo y la densidad ósea. El propósito de este estudio es comentar algunos enfoques terapéuticos empleados en la osteoporosis, destacando el mecanismo de acción del ranelato de estroncio que aumenta la formación de hueso y disminuye la resorción. La causa más común de osteoporosis en las mujeres es la disminución de los niveles de estrógeno durante la menopausia, lo que lleva a un aumento significativo en el recambio de masa ósea y el consiguiente desequilibrio entre la formación y reabsorción ósea con un aumento de la pérdida ósea y el deterioro de la estructura y fuerza óseas. El ranelato de estroncio sigue siendo una opción farmacológica eficaz y viable en la prevención de las fracturas vertebrales y del cuello femoral en mujeres posmenopáusicas y hombres adultos con osteoporosis, en cuanto a indicaciones, contraindicaciones y una cuidadosa evaluación de sus efectos y riesgos. Representa una alternativa a los medicamentos antirresortivos en caso de contraindicación, intolerancia o fracaso(AU)

The purpose of the treatment of osteoporosis is the primary and secondary prevention of fractures. The indications for therapeutic interventions in osteoporosis should be derived from the determination of the absolute risk of fracture, which takes into account the evaluation of risk factors and bone density. To comment on some therapeutic approaches used in osteoporosis, highlighting the mechanism of action of strontium ranelate that increases bone formation and reduces resorption. The most common cause of osteoporosis in women is the decrease in estrogen levels during menopause, which leads to a significant increase in the turnover of bone mass and the consequent imbalance between bone formation and resorption with an increase in bone loss and deterioration of bone structure and strength. Strontium ranelate continues to be an effective and viable pharmacological option in the prevention of vertebral and femoral neck fractures in postmenopausal women and adult men with osteoporosis, in terms of indications, contraindications and a careful evaluation of its effects and risks. It represents an alternative to antiresorptive drugs in case of contraindication, intolerance or failure(AU)

Comparative evaluation of remineralisation potential of bioactive glass, casein phosphopeptide-amorphous calcium phosphate and novel strontium-doped nanohydroxyapatite paste: An In-Vitro study

Background: Many studies explained the importance of remineralisation of early carious lesions with various remineralising agents. In the present study, we incorporated the remineralising agents in a dentifrice, applied that in artificial enamel caries and evaluated their remineralising potential and compared the efficacy among the three. Aim: To evaluate and compare the remineralisation potential of a dentifrice containing bioactive glass, casein phosphopeptide?amorphous calcium phosphate and novel laboratory synthesised strontiumdoped nanohydroxyapatite paste in artificial enamel caries. Methods and Materials: 120 enamel specimens were divided into 4 groups of 30 specimens each, based on the type of dentifrice applied: GI ? conventional toothpaste (control group), GII ? calcium sodium phosphosilicate (Novamin), GIII ? casein phosphopeptide?amorphous calcium phosphate (GC tooth mousse) and GIV? Novel strontiumdoped nanohydroxyapatite paste (SrnHAp paste). Specimens in all the groups were subjected to demineralisation, and calcium/phosphorous ratio was analysed followed by remineralisation and the mean calcium–phosphorus ratio was assessed using a scanning electron microscope and energy dispersing X?ray analysis. Statistical Analysis: Data were analysed using IBM SPSS Statistics for Windows Software, version 22 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to calculate the mean and standard deviation. Kruskal?Wallis, ANOVA and Mann–Whitney tests were used. The level of significance was set at 5%. Results and Conclusion: All except the control group showed a net increase in calcium and phosphorous values after application of the respective remineralising agents in respective groups. Inter?group comparison revealed that Group IV ? SrnHAp paste yields higher net calcium and phosphorous values than other groups. Hence, novel SrnHAp can be considered as the material of choice in remineralising early enamel carious lesions

Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats

Abstract This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Impacto clínico del estroncio y del zinc en los procesos de regeneración ósea y del cartílago, aproximación desde la biología hacia la clínica. Revisión de literatura / Clinical impact of strontium and zinc on bone and cartilage regeneration processes, an approach from biology to the clinic. Literature review

Muchos trastornos sistémicos como la artritis o la osteoporosis son patologías responsables de las alteraciones crónicas de la articulación temporomandibular, creando así un problema a largo plazo que afectan la calidad de vida de aquellas personas que las padecen. Actualmente no existe tratamiento curativo para dichas patologías, aunque sí de tipo paliativo, que en muchas ocasiones tienen efectos secundarios en el tiempo o una limitación en su efectividad y eficacia, por lo que se hace necesario buscar alternativas con la implementación de terapias regenerativas para el tratamiento de aquellas enfermedades que afectan el sistema musculoesquelético. En muchos estudios se discute sobre el papel fundamental que cumple el zinc y el estroncio en la génesis de tejido tanto cartilaginoso como óseo, así como la relevancia de incorporarlos con diversos biomateriales en procedimientos de regeneración, sin embargo, este tema no es claro aún y requieren más aten- ción por parte del clínico. El objetivo de este artículo es determinar la función cumplen el zinc y el estroncio en los procesos de regeneración del hueso y el cartílago desde una visión molecular y celular aplicada a la práctica clínica, con el fin de obtener nuevas alternativas en el tratamiento de diversas patologías y alteraciones musculoesqueléticas que mejoren las condiciones de salud oral de los pacientes, además de, contar con la revisión que nos aproxime a comprender los mecanismos de acción de diferentes moléculas que incorporadas a los biomateriales compatibles con el tejido duro y blando mejoren las condiciones biológicas para la regeneración.

Many systemic disorders such as arthritis or osteoporosis are pathologies responsible of temporomandibular joint chronic dysfunctions, thus creating a long-term problem that affects life ́s quality of those who suffer from them. Currently there is no curative treatment for these pathologies, although there is a palliative treatment, which in many cases have side effects over time or a limitation in their effectiveness and efficacy, so it is necessary to look for alternatives with the implementation of regenerative therapies for treatment of those diseases that affect musculoskeletal system. In many studies the fundamental role of zinc and strontium in genesis of both cartilaginous and bone tissue is discussed, as well as the relevance of incorporating them with various biomaterials in regeneration procedures, however, this issue is not clear yet and requires more attention from the clinician. The objective of this article is to determine function of zinc and strontium in regeneration processes of bone and cartilage from a molecular and cellular perspective applied to clinical practice, in order to obtain new alternatives in the treatment of various pathologies and musculoskeletal alterations that improve the oral health conditions of patients. In addition, this review brings us closer to understanding the mechanisms of action of different molecules that when incorporated into biomaterials compatible with hard and soft tissue improve the biological conditions for the regeneration.

Therapeutic effect of 90Sr application on infantile hemangioma in hair area and its influence on hair volume / 中华核医学与分子影像杂志

Objective:To investigate the clinical effect of 90Sr application on superficial hemangioma in hair area and its effect on the volume of hair. Methods:A total of 136 pediatric patients (55 males, 81 females, 1-30 months old; 136 lesions) with head hemangioma in the First Affiliated Hospital of Guangxi Medical University between February 2018 and October 2019 were enrolled. They were divided into 3 groups according to the hair density of tumor sites. Group A ( n=63, 3(2, 6) months old, male/female=27/36): the hair in tumor sites was as thick as the surrounding hair. Group B ( n=40, 3(2, 5) months old, male/female=17/23): the hair in tumor sites was thinner than the surrounding area. Group C ( n=33, 3(2, 6) months old, male/female=11/22): there was no hair growth in the tumor sites. All groups were treated with 90Sr application, and the total absorbed dose of each course was 10-30 Gy, which was divided into 8 times. Three to four months after the treatment, the efficacy and adverse reactions were evaluated and the volume of hair was divided into 3 grades according to the hair density of the tumor sites: flourishing, good growth and no growth. If the clinical effect was unsatisfied, a second course of treatment was conducted. Kruskal-Wallis rank sum test or χ 2 test was used for data analysis. Results:The differences of age ( H=0.01), gender ( χ 2=0.92) among group A, group B and group C were not significant (both P>0.05). The total recovery rates of 3 groups after two-course treatment were 88.9%(56/63), 95.0%(38/40) and 93.9%(31/33) respectively ( χ 2=1.49, P>0.05). Besides, the incidences of adverse reactions were 6.3%(4/63), 7.5%(3/40) and 9.1%(3/33) respectively ( χ 2=0.24, P>0.05). Three to four months after treatment, the hair on tumor sites in group A and B was rated as flourishing, 28 children in group C were rated as flourishing, 5 children were rated as good growth, and none of the children showed no growth. Conclusions:The 90Sr application has a good treatment effect on the small superficial hemangioma in the hair area of infants, and the amount of hair in the affected area can be restored to normal after treatment. This treatment is worthy of clinical application.

Application of 90Sr application in the treatment of cutaneous hemangioma / 中华核医学与分子影像杂志

Cutaneous hemangioma is a kind of benign skin vascular tumor caused by congenital abnormal vascular development. The rays emitted by 90Sr has a good effect on it. Meanwhile, 90Sr application is easy to operate, effective, with less side effects and painless. It is a method worthy of promotion in the treatment of skin hemangioma. This article reviews the application of 90Sr application in cutaneous hemangioma treatment.

Avaliação da morfologia hepática em ratos após administração do ranelato de estrôncio / Evaluation of hepatic morphology in rats after administration of strontium ranelate

Introdução: o fármaco ranelato de estrôncio (RE) é muito utilizado na terapêutica profilática e no controle da osteoporose. Age sistemicamente diminuindo a reabsorção e aumentando a formação óssea, apresentando eventos adversos pouco esclarecidos na literatura, à exemplo a síndrome DRESS com envolvimento hepático. Objetivo: avaliar a morfologia hepática em ratos norvegicus albinus após administração do RE. Metodologia: estudo experimental com 10 ratos, divididos aleatoriamente em dois grupos, Grupo Controle (GC), sem administração do RE, e Grupo Ranelato de Estrôncio (GRE), ambos acompanhados durante 15 dias, e, em seguida, sacrificados e o fígado de cada animal colocado para fixação no solução de formaldeído a 4% durante 48 horas. Após essa etapa, foram realizados os procedimentos necessários à análise pela microscopia óptica, com lâminas coradas pela hematoxilina e eosina, e picrosirius red.Resultados: nos GC e GRE foram encontradas alterações similares, como reação ductular, dilatação sinusoidal e fibrose perissinusoidal, com intensidades distintas entre os grupos, sendo a reação ductular mais proeminente no GC, e a dilatação sinusoidal e fibrose perissinusoidal mais pronunciada no GRE. Além disso, no GC foram evidenciados achados inflamatórios, como presença de infiltrado inflamatório misto e hiperplasia de células de Kupffer, não visualizados no GRE, implicando numa possível ação anti-inflamatória do RE. Conclusão: pode-se concluir que foram visualizadas diferenças nos achados morfológicos do parênquima hepático dos ratos tratados com o RE em comparação aos não tratados, ainda que esses achados não sejam suficientes para inferir a incidência de um processo patológico característico, como cirrose ou hepatite.

Introduction: the drug strontium ranelate (SR) is widely used in prophylactic therapy and in the control of osteoporosis. It acts by reducing reabsorption and increasing bone formation systemically, presenting unclear adverse events in the literature, such as the DRESS syndrome with hepatic involvement. Objective: to evaluate hepatic morphology in norvegicus albinus rats after SR administration. Methodology: experimental group with 10 rats, divided into two groups, randomly distributed, five from the Control Group (CG), without SR administration, and the other five from the Strontium Ranelate Group (SRG), both followed for 15 days, and then sacrificed and the liver of each animal placed for fixation in 4% formalin for 48 hours. After this step, the procedures necessary for the analysis by optical microscopy were performed, with blades stained by hematoxylin e eosin, and picrosirius red. Results: in CG and SRG, similar alterations were observed, such as ductular reaction, sinusoidal dilatation and perissinusoidal fibrosis, with distinct intensities between the groups, being the ductular reaction more prominent in the CG, and sinusoidal dilation and a perissinusoidal fibrosis more pronounced in the SRG. In addition, in the CG were evidenced inflammatory findings such as the presence of mixed inflammatory infiltrate and Kupffer cell hyperplasia, not visualized in the SRG, implying a possible anti-inflammatory action of SR. Conclusion: it can be concluded that differences were observed in the morphological findings of the hepatic parenchyma of rats treated with SR compared to untreated rats, although these findings are not sufficient to infer the incidence of a characteristic pathological process, such as cirrhosis or hepatitis.

Análise microtomografica e imunoistoquímica do osso peri-implantar em dimorfismo sexual com implantes funcionalizados com estrôncio / Microtomographic and immunohistochemical analysis of periimplant bone in sexual dimorphism with strontium functionalized implants

O presente trabalho tem por objetivo caracterizar a influência de esteróides gonadais e o dimorfismo sexual na microarquitetura do tecido ósseo formado ao redor de implantes funcionalizados por estrôncio e instalados na tíbia de ratos e ratas que foram divididos em 4 grupos experimentais. Os grupos SHAM F e SHAM M foram os grupos controle, submetidos a cirurgia fictícia, nas fêmeas e machos. O grupo OVX foram as fêmeas submetidas à cirurgia de ovariectomia bilateral e os ORQ foram os machos submetidos à orquiectomia. Após 30 dias das cirurgias para remoção das gônadas ou cirurgias fictícias, os animais foram submetidos à instalação dos implantes nas tíbias, cada animal recebeu 2 implantes, sendo 1 em cada metáfise tibial. A eutanásia foi realizada aos 60 dias após a instalação dos implantes. Os ossos tibiais foram coletados e processados laboratorialmente para a análise tridimensional através da avaliação microtomográfica (Micro-Ct), também foi realizada uma análise imunoistoquímica, com objetivo de analisar as respostas celulares quanto ao processo de reabsorção óssea, remodelação e mineralização. Concluiu-se que a funcionalização com estrôncio na superfície dos implantes interferiu no processo de reparo perimplantar, resultando em tecido ósseo com diferentes características microarquiteturais, de acordo com o gênero(AU)

The present work aims to characterize the influence of gonadal steroids and sexual dimorphism on the microarchitecture of bone tissue formed around strontium functionalized implants and installed in the tibia of rats and mice that were divided into 4 experimental groups. The SHAM F and SHAM M groups were the control groups, applying the fictitious surgery, in the latter and males. The OVX group were as submitted to bilateral ovariectomy surgery and the ORQ were the males related to the orchiectomy. After 30 days of surgery to remove the gonads or fictitious surgeries, the animals were infected by installing the implants in the tibiae, each animal completes 2 implants, 1 in each tibial metaphysis. Euthanasia performed 60 days after the implant installation. Tibial bones were collected and processed in the laboratory for a three-dimensional analysis through microtomographic evaluation (Micro-Ct), an immunohistochemical analysis was also carried out, with the objective of analyzing cellular responses regarding the process of bone resorption, remodeling and mineralization. It was concluded that strontium functionalization on the surface of the implants interfered in the process of perimplant repair, termination in bone tissue with different microarchitectural characteristics, according to gender(AU)

Caracterização e avaliação randomizada de superfícies de liga de titânio modificada por hidroxiapatita e hidroxiapatita incorporada com estrôncio em ratas saudáveis e osteoporóticas / Characterization and randomized evaluation of titanium alloy surfaces modified by hydroxyapatite and hydroxyapatite incorporated with strontium in healthy and osteoporotic female rats

Este estudo objetivou caracterizar os tratamentos de superfície com hidroxiapatita e hidroxiapatita modificada por estrôncio em duas concentrações (10 e 90%) sobre superfícies de liga de titânio, e avaliar a sua osseointegração em tíbias de ratas saudáveis e osteoporóticas. Foram utilizados parafusos de fixação e discos de liga de titânio, que foram divididos em grupos de acordo com a superfície: Usinada, Hap, HapSr 10% e HapSr 90%. Os tratamentos de superfícies foram realizados pelo método biomimético. Foi avaliado a morfologia, estrutura, composição química, molhabilidade, energia de superfície e integridade das superfícies. As superfícies também foram testadas in vivo, na qual os parafusos foram randomizados e instalados em tíbias de ratas saudáveis (controle) e osteoporóticas (OVX). A osseointegração foi avaliada pelo torque reverso, área de fluorocromos calceína e alizarina, área de contato entre tecido ósseo e parafuso e extensão linear de contato entre osso e parafuso 60 dias após a instalação. Nas análises laboratoriais observaram-se nas superfícies Hap, HapSr10% e HapSr90% filmes finos rugosos e presença de poros em escala nanométrica, presença de grupos químicos de Hap semelhante à do tecido ósseo, e aumento expressivo da molhabilidade e da energia de superfície. Nas análises in vivo de torque reverso, no grupo OVX os valores foram mais significativos para as superfícies contendo estrôncio (HapSr 10% e HapSr90%), enquanto no grupo controle a superfície de Hap apresentou maior torque para remoção do parafuso. A área de fluorocromos para calceína e a área óssea neoformada foi expressivamente maior na superfície de HapSr 10% do grupo controle. Em conclusão, as superfícies tratadas com as hidroxiapatitas melhoram a morfologia, composição e a reatividade da superfície, e apresentam um efeito promissor na osseointegração de parafusos em tíbias de ratas saudáveis e osteoporóticos(AU)

The objective of this study was to characterize the surface treatments with hydroxyapatite and hydroxyapatite modified by strontium in two concentrations (10 and 90%) on titanium alloy surfaces, and to evaluate their osseointegration in tibias of healthy and osteoporotic rats. Fixing screws and titanium alloy discs were used, which were divided into groups according to the surface: Machined, Hap, HapSr 10% and HapSr 90%. The surface treatments were carried out by the biomimetic method. The morphology, structure, chemical composition, wettability, free surface energy and surface integrity were evaluated. The surfaces were also tested in vivo, in which the screws were randomized and installed in the tibias of healthy (control) and osteoporotic (OVX) rats. Osseointegration was evaluated by reverse torque, area of fluorochromes calcein and alizarin, area of contact between bone tissue and screw and linear extent of contact between bone and screw 60 days after placement. Laboratory analyzes showed that Hap, HapSr10% and HapSr90% had thin, rough films and the presence of pores on a nanometer scale, the presence of Hap chemical groups similar to that of bone tissue, and a significant increase in wettability and surface energy. In the in vivo analyzes of reverse torque, in the OVX group the values were more significant for strontium-containing surfaces (HapSr 10% and HapSr90%), while in the control group the Hap surface showed greater torque for removing the screw. The fluorochromic area for calcein and the newly formed bone area were significantly greater on the HapSr 10% surface of the control group. In conclusion, surfaces treated with hydroxyapatites improve surface morphology, composition, and reactivity, and have a promoting effect on screw osseointegration in healthy and osteoporotic female rats(AU)

Desenvolvimento, caracterização e avaliação in vitro de cimento ósseo à base de nano hidroxiapatitas substituídas com magnésio, estrôncio e zinco / Development, characterization and in vitro evaluation of bone cement based on nano-hydroxyapatites substituted with magnesium, strontium and zinc

A incorporação de íons na estrutura da hidroxiapatita (HA) pode afetar sua estrutura, cristalinidade, solubilidade e citotoxicidade. Dentre os íons presentes na composição da apatita óssea, o magnésio (Mg2+), estrôncio (Sr2+) e zinco (Zn2+) são reconhecidos por promover a angiogênese e osteogênese. Portanto, as HAs substituídas podem apresentar melhor bioatividade, por fornecer íons com potencial de estimular a neoformação óssea nos locais enxertados. Nesse contexto, este estudo descreve a síntese, caracterização e comparação de uma série de nano-hidroxiapatitas (nHAs) substituídas e co-substituídas por Sr2+, Mg2+ ou Zn2+. Em seguida, foi desenvolvido um cimento ósseo à base das HAs com melhores resultados de citotoxicidade, associado ao DCPA, gelatina e quitosana. As nHAs foram caracterizadas físico-quimicamente usando diferentes técnicas. O método de co-precipitação foi eficaz para sintetizar HAs de dimensões nanométricas. Comparado a nHA pura, os difratogramas, espectros de FTIR e parâmetros de rede das nHAs substituídas e co-substituídas exibiram alterações, indicando que a incorporação de cátions resultou em distorções da rede da HA. Os testes de MTT demonstraram que as nHAs sintetizadas não foram citotóxicas, após contato direto com culturas de fibroblastos (L929) e pré-osteoblastos (MC3T3). Os resultados obtidos sugerem que as nHAs co-substituídas por Mg2+/Sr2+ e Zn2+/Sr2+ parecem induzir maior proliferação de células fibroblásticas e osteoblásticas, quando comparado a HA pura e substituída. Os cimentos ósseos desenvolvidos apresentaram capacidade de auto-endurecimento e resistência à lavagem. Além de possuírem alta molhabilidade e um perfil de liberação de íons Ca2+, Sr2+, Mg2+ e Zn2+, que está dentro das doses indicadas para estimular a proliferação de osteoblastos. Os cimentos exibiram excelente biocompatibilidade in vitro em culturas de células fibroblásticas, endoteliais e osteosblásticas. Os cimentos contendo nHAs co-substituídas por Mg2+/Sr2+ exibiram os melhores resultados de viabilidade celular. Após 24 horas de contato indireto com cultura de células fibroblásticas L929, o crescimento celular do grupo C2 foi maior que de todos os grupos em estudo (P < 0,01). Em cultura de células endoteliais EA.hy926, o percentual de células viáveis do grupo C3 foi significativamente maior que de todos os outros grupos, após 24 horas (p < 0,001). A citotoxicidade indireta em cultura de células pré-osteoblásticas MC3T3 revelou que após 48 horas, o grupo C3 apresentou maior viabilidade celular que todos os grupos em estudo (p < 0,01). O teste de formação de tubo sugere que todos os cimentos desenvolvidos possuem potencial angiogênico, sendo que os cimentos contendo nHAs co-substituídas por Zn2+/Sr2+ exibiram resultados significativamente superiores (p < 0,001). Apesar de ser necessário um maior número de testes de biocompatibilidade; a incorporação de íons na rede cristalina das nHAs, que são reconhecidos por afetar a angiogênese e a osteogênese, parece ter resultado no desenvolvimento de cimentos ósseos com potencial para promover a regeneração óssea.

The incorporation of ions into the HA lattice can affect its structure, crystallinity, solubility and cytotoxicity. From the ions present in the composition of bone apatite, Mg2+, Sr2+ and Zn2+ are recognized for promoting angiogenesis and osteogenesis. The substituted HAs can be present better bioactivity for supplying ions with potential to stimulate bone neoformation in grafted sites. This study described the synthesis, characterization and comparison of a range of substituted and co-substituted nHAs contained Sr2+, Mg2+ or Zn2+. Then, it developed bone cement based on HAs with better cytotoxicity results, associated with DCPA, gelatin and chitosan. The nHAs were physicochemically characterized using different techniques. The co-precipitation method was effective for synthesizing HAs with nanometric dimensions. Compared to pure nHA, the diffractograms, FTIR spectra and lattice parameters of the substituted and co-substituted nHAs showed changes, indicating that the incorporation of cations resulted in distortions of the HA lattice. MTT tests demonstrated that the all synthesized nHAs were not cytotoxic after direct contact with fibroblasts (L929) and pre-osteoblasts (MC3T3) cultures. MTT results suggest that Mg2+/Sr2+ and Zn2+/Sr2+ co-substituted nHAs seem to induce more proliferation of fibroblastic and osteoblastic than pure and Mg2+, Sr2+ and Zn2+ substituted nHAs. Bone cements developed showed self-hardening and washout resistance. Also, they Exhibited high wettability and ion release profile with non-toxic concentrations of Ca2+, Sr2+, Mg2+ and Zn2+, range within indicated doses to stimulate the proliferation of osteoblasts. The cement exhibited excellent in vitro cytocompatibility in fibroblastic, endothelial and osteoblastic cell cultures. Cement containing Mg2+/Sr2+ co-substituted nHAs showed better results of the cell viability. After 24 hours of indirect contact with L929 fibroblast culture, the cell growth in the C2 group was highest than all study groups (P <0.01). In EA.hy926 endothelial culture, the cell viability of the C3 group was significantly highest than all other groups after 24 hours (p <0.001). The indirect cytotoxicity in MC3T3 pre-osteoblastic culture revealed that after 48 hours, the C3 group showed the greatest cell viability than all the study groups (p <0.01). The tube formation assay suggests that all cement have angiogenic potential, being that the cements containing Zn2+ / Sr2+ co-substituted nHAs exhibited significantly better results (p < 0,001). Despite being necessary to perform a more significant number of biocompatibility tests, the incorporation of ions into the nHA lattice, which are recognized for affects angiogenesis and osteogenesis, may have resulted in the development of bone cements with the potential to promoting bone regeneration.

Effects of strontium-modified titanium surfaces on adhesion, migration and proliferation of bone marrow mesenchymal stem cells and expression of bone formation-related genes / 中国组织工程研究

BACKGROUND: Strontium promotes bone formation, and reduces bone resorption. Strontium-modified titanium implant surface has been the focus of research in implant osseointegration under osteoporotic conditions. OBJECTIVE: To investigate the cell adhesion, stretch, and migration of advanced strontium-modified titanium surfaces using bone marrow mesenchymal stem cells isolated from rats. METHODS: Strontium-modified titanium surfaces were produced by sequential treatments with 5 mol/L NaOH, 100 mmol/L strontium acetate, and heated at 600 or 700 °C for 1 hour. After heat treatment, half the samples were soaked in deionized water at 80 °C for 24 hours, then washed and dried. The pure titanium served as control group, and there were five groups. The whole bone marrow adherence method was used to separate bone marrow mesenchymal stem cells from the rats. The modified titanium sheets were placed in 24-well plates and cultured in cell suspension. Cell adhesion and cell proliferation were assessed using cell counting kit-8 assay. After bone marrow mesenchymal stem cells were with the titanium sheet for 24 hours, the actin was stained to observe cell adhesion and stretch. The migration of bone marrow mesenchymal stem cells on different titanium surfaces was investigated using cell scratch test and fluorescence staining. The expression levels of collagen type І, Runx2, osteoprotegerin, RANKL and osteopontin were detected by qRT-PCR. RESULTS AND CONCLUSION: Strontium-modified titanium could promote the stretch and migration of bone marrow mesenchymal stem cells. The number of proliferative cells in the Sr700 group was significantly higher than that in the Sr600 group at 5 days (P < 0.01). On day 14, strontium-modified titanium promoted the expression of collagen type І, Runx2, and osteopontin. In summary, strontium-modified titanium can promote adhesion, spreading, migration and proliferation of rat bone marrow mesenchymal stem cells. Moreover, hydration treatment can enhance the osteogenic activity of rat bone marrow mesenchymal stem cells.

Calcium hydrogen phosphate dehydrate combined with gelatin and recombinant human bone morphologic protein 2/7 for repair of bone defects in rabbits / 中国组织工程研究

BACKGROUND: Studies have shown that the osteogenic ability of 10% strontium-doped calcium hydrogen phosphate dihydrate is higher than that of calcium hydrogen phosphate dihydrate and 5% strontium-doped calcium hydrogen phosphate dihydrate, but also found that the pore structure of 10% strontium-doped calcium hydrogenphosphate dihydrate is not ideal, and the early osteogenic effect is not satisfactory. OBJECTIVE: To investigate the osteogenic effect of the composite of 10% strontium-doped calcium hydrogenphosphate dehydrate and gelatin and recombinant human bone morphogenetic protein 2/7 (rhBMP2/7). METHODS: Gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate and gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate material containing 0.04 g/L and 1 g/L rhBMP2/7 were prepared respectively. Forty-five rabbit models of bilateral mandibular defects were prepared and then divided into five groups. In the blank control group, no material was implanted. 10% strontium-doped calcium hydrogen phosphate dihydrate (control group) and gelatin-10% strontium-doped calcium hydrogen phosphate dihydrate (gelatin group), 0.04 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (0.04 g/L rhBMP2/7 group), and 1 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (1 g/L rhBMP2/7 group) were implanted in the remaining four groups, respectively. Bone defect specimens were taken at 4, 8 and 12 weeks after surgery, and were examined by cone beam CT and immunohistochemistry. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China. RESULTS AND CONCLUSION: Cone beam CT examination revealed that at 8 weeks after surgery, bone repair was basically completed and the new bone tissue was almost fused with the surrounding tissue in the 1 g/L rhBMP2/7 group. Most of defect area was repaired, and the edge of new bone was unsmooth in the 0.04 g/L rhBMP2/7 and gelatin groups. Bone defect in the control group partially repaired. At 12 weeks after surgery, bone repair was completed in the gelatin, 0.04 rhBMP2/7 and 1 g/L rhBMP2/7 groups. Immunohistochemistry revealed that at 4 and 8 weeks after surgery, type I collagen expression in the 1 g/L rhBMP2/7 group was significantly higher than that in the other four groups (P 0.05). These results suggest that the addition of gelatin and 1 g/L rhBMP2/7 to 10% strontium-doped calcium hydrogenphosphate dihydrate can promote the repair of bone defects.

Research progress on trace elements-modified titanium implant surfaces / 口腔疾病防治

@#Traditional titanium implants are bioinert, and some biological properties, such as osteogenic and antibacterial properties, can be obtained by adding different trace elements to their surfaces. These trace elements can help enhance implant-bone binding and effectively prevent peri-implantitis. Different trace elements have different advantages, and different modification methods can also affect the biological properties. In this paper, the biological properties of titanium implant surfaces modified by trace elements were reviewed. The results of a literature review show that implant surfaces modified by fluoride, silver, zinc, manganese, etc. can inhibit the growth of bacteria and reduce the negative impact on normal cells from bacteria. Other elements, such as strontium, tantalum and cobalt, can promote the differentiation of osteoblasts on the surface of titanium implants, improve the activity of alkaline phosphatase, and improve the expression of osteogenic genes, thus increasing the amount of bone formation and enhancing the strength of implant-bone integration. Most elements have multiple properties, and the combined application of two or more elements can yield more biological properties than a single element. Since there are many trace elements in the human body, there is still a wide research space available in the field of the surface modification of dental implants by trace elements.

Research progress in the osteogenetic mechanism of strontium / 华西口腔医学杂志

Strontium (Sr) is an essential trace element and widely exists in nature. It plays an important role in the in vivo regulation of bone metabolism. Sr locates below Fe in the periodic table, and its chemical structure and polarity are similar to those of Ca. It can induce bone mesenchymal stem cells to differentiate into osteoblasts by inhibiting the activity of osteoclasts and reducing bone resorption. It promotes bone formation through a series of related pathways. The mechanism of Sr regulation of bone metabolism has been extensively researched in recent years. The current study aims to investigate the mechanism of Sr and provide a theoretical basis for its clinical application.

Preliminary development and manufacturing of radioactive sewage purification device / 中国职业医学

OBJECTIVE: To develop a radioactive sewage purification device that can effectively filter the nuclides in low-level nuclide-contaminated wastewater. METHODS: The radioactive sewage purification device was composed of lifting pump, stack filter, multi-medium filter, security filter, tubular ultrafiltration membrane, high-pressure pump and reverse osmotic membrane. The combined process of adsorption-ultrafiltration-reverse osmosis was used to separate radioactive elements from wastewater by reverse osmosis membrane separation system. Through two-stage multi-medium filter circulation system circulation treatment, radioactive sewage was purified. The flow rate of water treatment is 20 L/min. The filtration efficiency and purification efficiency of the device were tested by filtration experiments on elements containing radionuclide and purification experiments on radionuclide.RESULTS: The filtration efficiency on iodine, potassium, strontium and cesium, that are the common elements in radioactive sewage samples were 97.88%, 98.38%, 99.99% and 99.80%, respectively. The single purification efficiency of radionuclide ~(40)K in low-level radioactive sewage was over 90.00%. CONCLUSION: The device has high filtering efficiency for common elements such as iodine, potassium, strontium and cesium in sewage and high removal rate of radioactive activity for sewage containing ~(40)K. It can be further optimized and transformed into a suitable radioactive sewage water purifier.

Primary mucoepidermoid carcinoma of the bulbar conjunctiva

A 58-year-old male presented with redness for 1 year and dimness of vision for 2 years in his left eye. Excision biopsy from an inferotemporal conjunctival mass revealed high-grade mucoepidermoid carcinoma (MEC) with lymphovascular invasion and positive margins. The tumor bed was irradiated to 80 Gy using strontium 90 β-applicator. After 13 months, fine-needle aspiration cytology from a suspicious preauricular lymphadenopathy found metastatic cells. Ipsilateral supra-omohyoid neck dissection showed three positive nodes out of 15, and the left neck was irradiated. He is disease free at present, 12 months from external beam radiation therapy completion. With 48 cases reported in the literature, conjunctival MEC remains a rare condition, possibly in part due to clinicopathological underdiagnosis. This is unfortunate, given that this cancer is more aggressive, has a poorer prognosis, and warrants more vigorous treatment than squamous cell carcinoma, which it may be misdiagnosed as in the absence of appropriate staining and pathological review

Strontium ranelate improving metabolic imbalance in oim mice of osteogenesis imperfecta: The dual mechanism / 第二军医大学学报

Objective: To explore the dual effects of strontium ranelate (SrR) on primary osteoblasts and osteoclasts using an osteogenesis imperfecta (OI) model oim mouse. Methods: The osteoblasts were obtained by digesting the calvaria of one-week-old homozygote oim/oim mice and wild type (wt/wt) mice with type I collagenase. The osteoclasts were obtained by inducing the bone marrow mononuclear cells derived from the long bone of oim/oim mice and wt/wt mice aged between five and seven weeks old. SrR with different concentrations (1 mmol/L and 10 mmol/L) was used to stimulate the cells. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to quantify the expression of osteoblast differentiation-related genes (Runt-related transcription factor 2 [Runx2], alkaline phosphatase [ALP] and osteocalcin [OCN]), osteoclast differentiation-related genes (calcitonin receptor [Calcr], tartrate-resistant acid phosphatase [Trap] and cathepsin K [CTSK]), and osteoclast differentiation-related transcription factors (cellular oncogene fos [c-fos] and nuclear factor of activated T-cell c1 [NFATc1]). The osteoblast differentiation and mineralization were evaluated by ALP staining and alizarin red S staining. The osteoclastogenesis and resorption activity of the osteoclasts were evaluated by Trap staining and pit formation assay. The effect of SrR on cell viability of osteoblasts and osteoclasts was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: qRT-PCR and Western blotting showed that the expression levels of Runx2, ALP, and OCN in oim/oim mice were significantly increased at mRNA and protein levels after stimulation with SrR in a dose-dependent manner (all P<0.05). In comparison, SrR caused significant decreases in Calcr, Trap, CTSK, c-fos, and NFATc1 expression (all P<0.05). ALP staining and alizarin red S staining demonstrated that SrR stimulation significantly increased osteoblast differentiation and mineralization of oim/oim mice (all P<0.05). Trap staining and pit formation assay showed that SrR significantly decreased the formation number of osteoclasts and inhibited the resorption activity of osteoclasts in oim/oim mice (all P<0.05). MTT assay showed that 1 mmol/L and 10 mmol/L SrR had no cell cytotoxicity on osteoblasts or osteoclasts of oim/oim mice. Conclusion: SrR can improve the imbalance of bone metabolism in OI model oim mouse, which might involve the increases in osteoblast differentiation and mineralization and decreases in formation and resorption of the osteoclasts.

Differentiation Capacity of Monocyte-Derived Multipotential Cells on Nanocomposite Poly(e-caprolactone)-Based Thin Films

BACKGROUND: Lonocyte-derived multipotential cells (MOMCs) include progenitors capable of differentiation into multiple cell lineages and thus represent an ideal autologous transplantable cell source for regenerative medicine. In this study, we cultured MOMCs, generated from mononuclear cells of peripheral blood, on the surface of nanocomposite thin films. METHODS: For this purpose, nanocomposite Poly(e-caprolactone) (PCL)-based thin films containing either 2.5 wt% silica nanotubes (SiO2ntbs) or strontium hydroxyapatite nanorods (SrHAnrds), were prepared using the spin-coating method. The induced differentiation capacity of MOMCs, towards bone and endothelium, was estimated using flow cytometry, real-time polymerase chain reaction, scanning electron microscopy and fluorescence microscopy after cells' genetic modification using the Sleeping Beauty Transposon System aiming their observation onto the scaffolds. Moreover, Wharton's Jelly Mesenchymal Stromal Cells were cultivated as a control cell line, while Human Umbilical Vein Endothelial Cells were used to strengthen and accelerate the differentiation procedure in semi-permeable culture systems. Finally, the cytotoxicity of the studied materials was checked with MTT assay. RESULTS: The highest differentiation capacity of MOMCs was observed on PCL/SiO2ntbs 2.5 wt% nanocomposite film, as they progressively lost their native markers and gained endothelial lineage, in both protein and transcriptional level. In addition, the presence of SrHAnrds in the PCL matrix triggered processes related to osteoblast bone formation. CONCLUSION: To conclude, the differentiation of MOMCs was selectively guided by incorporating SiO2ntbs or SrHAnrds into a polymeric matrix, for the first time.