Titanium micro-nano textured surface with strontium incorporation improves osseointegration: an in vivo and in vitro study.

OBJECTIVES: This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nano textured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model. METHODOLOGY: Ti commercially pure (cp-Ti) implants were installed bilaterally in the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C); (2) Micro-nano textured surface treatment (MN); (3) Micro-nano textured surface with Sr2+ addition (MNSr); and (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). In total, two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (µ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy. RESULTS: SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. TR test indicated greater osseointegration in the 45-day period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, in which an increase in bone-implant contact was found in groups MN (15 days) and MNSr (45 days) compared to the control group. Gene expression analysis of osteogenic activity markers showed modulation of various osteogenesis-related genes. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation markers. CONCLUSIONS: Micro-nano textured surface and Sr addition can effectively improve and accelerate implant osseointegration and is, therefore, an attractive approach to modifying titanium implant surfaces with significant potential in clinical practice.

Use of Zebrafish (Danio rerio) for Biosafety Evaluation of Strontium Nanostructured Hydroxyapatite.

Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials.

Size-Dependent Blue Emission from Europium-Doped Strontium Fluoride Nanoscintillators for X-Ray-Activated Photodynamic Therapy.

Successful implementation of X-ray-activated photodynamic therapy (X-PDT) is challenging because most photosensitizers (PSs) absorb light in the blue region, but few nanoscintillators produce efficient blue scintillation. Here, efficient blue-emitting SrF2:Eu scintillating nanoparticles (ScNPs) are developed. The optimized synthesis conditions result in cubic nanoparticles with ≈32 nm diameter and blue emission at 416 nm. Coating them with the meso-tetra(n-methyl-4-pyridyl) porphyrin (TMPyP) in a core-shell structure (SrF@TMPyP) results in maximum singlet oxygen (1O2) generation upon X-ray irradiation for nanoparticles with 6TMPyP depositions (SrF@6TMPyP). The 1O2 generation is directly proportional to the dose, does not vary in the low-energy X-ray range (48-160 kVp), but is 21% higher when irradiated with low-energy X-rays than irradiations with higher energy gamma rays. In the clonogenic assay, cancer cells treated with SrF@6TMPyP and exposed to X-rays present a significantly reduced survival fraction compared to the controls. The SrF2:Eu ScNPs and their conjugates stand out as tunable nanoplatforms for X-PDT due to the efficient blue emission from the SrF2:Eu cores; the ability to adjust the scintillation emission in terms of color and intensity by controlling the nanoparticle size; the efficient 1O2 production when conjugated to a PS and the efficacy of killing cancer cells.

A nontoxic strontium nanoparticle that holds the potential to act upon osteocompetent cells: An in vitro and in vivo characterization.

Estrogen deficiency, long-term immobilization, and/or aging are commonly related to bone mass loss, thus increasing the risk of fractures. One option for bone replacement in injuries caused by either traumas or pathologies is the use of orthopedic cement based on polymethylmethacrylate (PMMA). Nevertheless, its reduced bioactivity may induce long-term detachment from the host tissue, resulting in the failure of the implant. In view of this problem, we developed an alternative PMMA-based porous cement (pPMMA) that favors cell invasion and improves osteointegration with better biocompatibility. The cement composition was changed by adding bioactive strontium-nanoparticles that mimic the structure of bone apatite. The nanoparticles were characterized regarding their physical-chemical properties, and their effects on osteoblasts and osteoclast cultures were assessed. Initial in vivo tests were also performed using 16 New Zealand rabbits as animal models, in which the pPMMA-cement containing the strontium nanoparticles were implanted. We showed that the apatite nanoparticles in which 90% of Ca2+ ions were substituted by Sr2+ (NanoSr 90%) upregulated TNAP activity and increased matrix mineralization. Moreover, at the molecular level, NanoSr 90% upregulated the mRNA expression levels of, Sp7, and OCN. Runx2 was increased at both mRNA and protein levels. In parallel, in vivo tests revealed that pPMMA-cement containing NanoSr 90%, upregulated two markers of bone maturation, OCN and BMP2, as well as the formation of apatite minerals after implantation in the femur of rabbits. The overall data support that strontium nanoparticles hold the potential to up-regulate mineralization in osteoblasts when associated with synthetic biomaterials.

Hidrogel 3D incorporado com biovidro para sistema drug delivery: caracterização e estudo in vitro / 3D Hydrogel Incorporated with bioactive glass and drug delivery system: characterization and In vitro study

Atualmente há diversos tratamentos para a osteoporose, porém a maioria deles pode corroborar com o surgimento de outras complicações sistêmicas, para isso é de suma importância o desenvolvimento de terapias locais, visando diminuir ou eliminar os efeitos colateriais causados por medicamentos de uso oral. O objetivo nesse projeto foi avaliar a influência de hidrogéis, com sistema drug delivery, incorporados com partículas de vidro bioativo funcionalizadas com diferentes medicamentos, na osteogênese in vitro. Partículas de vidro bioativo foram sintetizadas e caracterizadas. Em seguida, foram funcionalizadas com os fármacos raloxifeno e ranelato de estrôncio usando a técnica sonoquímica. Hidrogéis de alginato foram sintetizados e incorporados com as partículas funcionalizadas usando impressão 3D em dimensões específicas. Os hidrogéis foram caracterizados por microscopia eletrônica de varredura, análise de intumescimento e molhabilidade. Em testes in vitro, os hidrogéis foram cortados em medidas menores e usados para culturas de células para avaliar a atividade e diferenciação celular para osteogênese. Células mesenquimais foram isoladas de ratas ovariectomizadas, diferenciadas em osteoblastos e co-cultivadas com os hidrogéis. Viabilidade celular, conteúdo de proteína total, atividade de fosfatase alcalina, morfologia celular e formação de nódulos de mineralização foram analisados em intervalos de tempo definidos. Os dados quantitativos foram submetidos aos testes estatísticos de normalidade Kolmogorov-Smirnov, seguidos pelo teste não paramétrico Kruskal Walis e teste multiplo de Dunn, com nível de significância de 5%. A caracterização morfológica e físico-química evidenciou o sucesso da referida metodologia em confeccionar o novo biomaterial. Nos testes in vitro, todos os grupos de hidrogéis impressos 3D não se mostraram citotóxicos e permitiram a diferenciação celular. A atividade de fosfatase alcalina não apresentou diferença entre os grupos. Por meio da análise da morfologia celular por fluorencência direta foi possível observar que em todos os grupos com excessão ao HBRx as células exibiam morfologia poligonal de forma íntegra, todos os grupos apresentaram células aderidas na superfície dos materiais, sendo que a maior quantidade de células foi observada no grupo hidrogel com vidro bioativo incorporado com ranelato de estrôncio. Na análise da formação de nódulos de mineralização, todos os grupos apresentaram a formação dos nódulos, exceto o grupo HBRx. Os resultados evidenciaram sucesso na produção de todos os novos biomateriais, HP, HB HBRx e HBSr tanto na síntese quanto na impressão 3D, conforme verificado nos testes de MEV, EDS e Raman, enquanto nos testes in vitro os grupos com vidro bioativo, em sua maioria, apresentaram resultados positivos para o uso na engenharia tecidual. De modo geral hidrogéis impresso 3D com vidro bioativo sem fármaco (HB) e incorporado com fármaco ranelato de estrôncio (HBSr) são os biomateriais que se mostraram mais promissores em comparação aos demais grupos. (AU)

Currently, there are several treatments for osteoporosis; however, most of them can lead to the emergence of other systemic complications. Therefore, it is of utmost importance to develop local therapies aiming to reduce or eliminate the side effects caused by orally administered medications. The objective of this project was to evaluate the influence of hydrogels with drug delivery systems incorporated with bioactive glass particles functionalized with different drugs on in vitro osteogenesis. Bioactive glass particles were synthesized and characterized. Subsequently, they were functionalized with the drugs raloxifene and strontium ranelate using sonochemical technique. Alginate hydrogels were synthesized and incorporated with the functionalized particles using 3D printing in specific dimensions. The hydrogels were characterized by scanning electron microscopy, swelling analysis, and wettability assessment. In in vitro tests, the hydrogels were cut into smaller sizes and used for cell cultures to assess cell activity and differentiation for osteogenesis. Mesenchymal cells were isolated from ovariectomized rats, differentiated into osteoblasts, and co-cultured with the hydrogels. Cell viability, total protein content, alkaline phosphatase activity, cellular morphology, and mineralization nodule formation were analyzed at defined time intervals. Quantitative data were subjected to Kolmogorov-Smirnov normality tests, followed by non-parametric Kruskal-Wallis and multiple Dunn tests, with a significance level of 5%. The morphological and physicochemical characterization demonstrated the success of the methodology in fabricating the new biomaterial. In the in vitro tests, all groups of 3D-printed hydrogels were non-cytotoxic and allowed cell differentiation. Alkaline phosphatase activity showed no difference among the groups. Through direct fluorescence-based cellular morphology analysis, it was observed that cells in all groups except HBRx exhibited intact polygonal morphology, with cells adhering to the material surfaces in all groups. The highest quantity of cells was observed in the hydrogel group incorporating bioactive glass with strontium ranelate. In the mineralization nodule formation analysis, all groups showed nodule formation except for the HBRx group. The results demonstrated successful production of all new biomaterials (HP, HB, HBRx, and HBSr) in both synthesis and 3D printing, as verified by SEM, EDS, and Raman tests. Meanwhile, in vitro testing showed that groups with bioactive glass mostly exhibited positive results for tissue engineering purposes. Overall, 3D-printed hydrogels with bioactive glass without drugs (HB) and incorporated with strontium ranelate (HBSr) proved to be the most promising biomaterials compared to the other groups (AU)

Assessment of carbon, oxygen, strontium, and lead isotopic variation in modern Colombian teeth: An application to human identification.

Colombia faces the complex humanitarian challenges of locating approximately 100,000 missing persons and identifying thousands who are deceased. Identification is a difficult task in many cases, because the skeletonized bodies are deteriorated, missing person data are unavailable for comparison, and the provenance of the remains is often totally unknown. Isotopic analysis of human tissues (e.g., bone, hair, nails, and teeth) aid in the identification process of unknown individuals because they can provide valuable information on possible geographic origin. This project evaluated the isotopic variability of carbon (C), oxygen (O), strontium (Sr), and lead (Pb) in modern Colombian teeth according to city, department (a political designation similar to "state" in the US or Mexico), and one of four geographically determined regions of origin; and assessed its utility for human identification in Colombia. Isotopic data (O-C-Sr-Pb) were analyzed from modern Colombians originating from the cities of Bogotá, Cali, and Neiva (n = 95); and these data were compiled with published Colombian data of individuals mainly from the city of Medellín (n = 61). Results indicate a wide range and overlap of O-C-Sr-Pb isotopic distribution according to the defined categories. However, differences between coastal and lowland individuals are observed when using δ18 O values, and differences between mountainous regions are observed when using 87 Sr/86 Sr values. In addition, this study suggests that the usefulness of isotopic analysis for unidentified individuals in Colombia would be with assigning them geographically using the designations of North, Central Andes, Eastern Andes, or Southwest Andes versus making classifications at a city or department level.

Strontium-driven physiological to pathological transition of bone-like architecture: A dose-dependent investigation.

Whilst strontium (Sr2+) is widely investigated for treating osteoporosis, it is also related to mineralization disorders such as rickets and osteomalacia. In order to clarify the physiological and pathological effects of Sr2+ on bone biomineralization , we performed a dose-dependent investigation in bone components using a 3D scaffold that displays the hallmark features of bone tissue in terms of composition (osteoblast, collagen, carbonated apatite) and architecture (mineralized collagen fibrils hierarchically assembled into a twisted plywood geometry). As the level of Sr2+ is increased from physiological-like to excess, both the mineral and the collagen fibrils assembly are destabilized, leading to a drop in the Young modulus, with strong implications on pre-osteoblastic cell proliferation. Furthermore, the microstructural and mechanical changes reported here correlate with that observed in bone-weakening disorders induced by Sr2+ accumulation, which may clarify the paradoxical effects of Sr2+ in bone mineralization. More generally, our results provide physicochemical insights into the possible effects of inorganic ions on the assembly of bone extracellular matrix and may contribute to the design of safer therapies for treating osteoporosis. STATEMENT OF SIGNIFICANCE: Physiological-like (10% Sr2+) and excess accumulation-like (50% Sr2+) doses of Sr2+ are investigated in 3D biomimetic assemblies possessing the high degree of organization found in the extracellular of bone. Above the physiological dose, the organic and inorganic components of the bone-like scaffold are destabilized, resulting in impaired cellular activity, which correlates with bone-weakening disorders induced by Sr2+.

A simple assessment of the effect of strontium on the urinary excretion of calcium in Sprague Dawley rats.

This study was aimed at investigating the impact of varying concentrations of strontium (Sr) on calcium (Ca) excretion via the urine and determine its impact on kidney stone formation. Twenty adult male Sprague Dawley rats weighing between 200 and 300 g were selected. The rats were randomly divided into four groups of five. One group was used as a control group while the other three groups were experimental. The diet of the rats was modulated over a 12 week period to investigate the impact of Sr on the urinary excretion of Ca. Urinary samples were collected every 2 weeks from the rats. The rats were fed water ad libitum. After the study the rats were euthanised and their kidneys harvested. Urine and kidney samples from the rats were analysed using Total Reflection X-Ray Fluorescence (TXRF). In the urine excretion of Ca increased with increased intake of Sr in the diet. Sr excretion via the urine also increased with increased dietary intake. There was a correlation of 0.835 at the significance level of 0.01 between Ca and Sr in the urine. However, for the kidneys, the varying concentration of Sr did not impact the retention of Ca in the kidneys. There was increased retention of Sr in the kidneys with increased dietary intake. In this study an increase of Sr in the diet resulted in an increase in urinary excretion of Ca.

Electrospun polylactic acid scaffolds with strontium- and cobalt-doped bioglass for potential use in bone tissue engineering applications.

The development of nanoscale biomaterials associated with polymers has been growing over the years, due to their important structural characteristics for applications in biological systems. The present study aimed to produce and test polymeric scaffolds composed of polylactic acid (PLA) fibers associated with a 58S bioglass doped with therapeutic ions for use in tissue engineering. Three 58S Bioglass was obtained by the sol-gel route, pure and doped with 5% strontium and cobalt ions. Solutions of 7% PLA was used as control and added the three different bioglass, 4% of 58S bioglass (PLA-BG), 4% bioglass-doped strontium (PLA-BGSr) and 4% bioglass-doped cobalt (PLA-BGCo). Scaffolds were produced through electrospinning process, and was characterized chemical and morphologically. The in vitro tests were performed using mesenchymal cells cultures from femurs of nine rats, grown in osteogenic supplemented total culture medium. After osteoblastic differentiation induction cell viability, alkaline phosphatase activity, total protein content quantification, and visualization of mineralization nodule tests were performed. Analysis of normal distribution used the Shapiro-Wilk test (nanofibers diameter and biological assay). Data were compared using the Kruskal-Wallis nonparametric test (p = 0.05). The bioglasses produced proved to be free of nitrate, chlorinated and nano-sized, with effective incorporation of therapeutic ions in their structure. All materials showed cell viability (>70%), total protein production, and alkaline phosphatase activity. It was possible to develop polylactic acid scaffolds associated with 58S bioglass doped with therapeutic ions without cytotoxicity. Scaffolds characteristics appear to sustain its application in bone tissue engineering.

Magnesium (Mg2 +), Strontium (Sr2 +), and Zinc (Zn2 +) Co-substituted Bone Cements Based on Nano-hydroxyapatite/Monetite for Bone Regeneration.

New bone cement type that combines Sr2 + /Mg2 + or Sr2 + /Zn2 + co-substituted nano-hydroxyapatite (n-HAs) with calcium phosphate dibasic and chitosan/gelatin polymers was developed to increase adhesion and cellular response. The cements were physicochemically described and tested in vitro using cell cultures. All cements exhibited quite hydrophilic and had high washout resistance. Cement releases Ca2 + , Mg2 + , Sr2 + , and Zn2 + in concentrations that are suitable for osteoblast proliferation and development. All of the cements stimulated cell proliferation in fibroblasts, endothelial cells, and osteoblasts, were non-cytotoxic, and produced apatite. Cements containing co-substituted n-HAs had excellent cytocompatibility, which improved osteoblast adhesion and cell proliferation. These cements had osteoinductive potential, stimulating extracellular matrix (ECM) mineralization and differentiation of MC3T3-E1 cells by increasing ALP and NO production. The ions Ca2 + , Mg2 + , Zn2 + , and Sr2 + appear to cooperate in promoting osteoblast function. The C3 cement (HA-SrMg5%), which was made up of n-HA co-substituted with 5 mol% Sr and 5 mol% Mg, showed exceptional osteoinductive capacity in terms of bone regeneration, indicating that this new bone cement could be a promising material for bone replacement.

Use of strontium isotope ratios in geolocation of Guatemalan population: Potential role in identification of remains.

Within post-conflict communities, attempts to identify and repatriate unidentified and missing individuals poses a difficult task. As current forensic strategies commonly lack the capacity to provide region of origin assessments, forensic anthropologists/investigators are often unable to identify sources of DNA for kinship analysis. Using Thermal Ionization Mass Spectrometry (TIMS), hair samples from 10 volunteers were used to assess the variation in strontium isotope ratios (87 Sr/86 Sr) between extant people in Guatemala City and Coban; with a leach (external) and digest (dietary) signal analyzed for each sample. A two-way anova demonstrated that the difference between 87 Sr/86 Sr of Guatemala City and Coban was statistically significant (F [1, 16] = 259.839, p < 0.05), with no statistically significant differences observed between leach and digest 87 Sr/86 Sr (F [1,16] = 4.319, p = 0.054). Overall, individuals from Coban demonstrate 87 Sr/86 Sr comparable to previously recorded baseline values, demonstrating a minimal change in diet which is reflected in associated surveys. Volunteers from Guatemala City, however, show a marked shift in 87 Sr/86 Sr away from predicted values highlighting the potential influence of imported goods. The results here highlight the applicability of 87 Sr/86 Sr in hair to serve as a potential tool to support the identification of unknown individuals in Guatemala in a forensic context.

Can strontium replace calcium in bioactive materials for dental applications?

The substitution of calcium with strontium in bioactive materials has been promising but there has been some concern over the material instability and possible toxicity. The aim of this research was the synthesis and characterization of calcium and strontium substituted bioactive materials and assessment of interactions with local tissues and peripheral elemental migration in an animal model. A bioactive glass, hydroxyapatite and hydraulic calcium silicate with 50% or 100% calcium substitution with strontium were developed and the set materials were characterized immediately after setting and after 30 and 180-days in solution. Following subcutaneous implantation, the local (tissue histology, elemental migration) and systemic effects (elemental deposition after organ digestion) were assessed. The strontium-replaced silicate cements resulted in the synthesis of partially substituted phases and strontium leaching at all-time points. The strontium silicate implanted in the animal model could not be retrieved in over half of the specimens showing the high rate of material digestion. Tissue histology showed that all materials caused inflammation after 30 days of implantation however this subsided and angiogenesis occurred after 180 days. Strontium was not detected in the local tissues or the peripheral organs while all calcium containing materials caused calcium deposition in the kidneys. The tricalcium silicate caused elemental migration of calcium and silicon in the local tissues shown by the elemental mapping but no deposition of calcium was identified in the peripheral organs verified by the assessment of the digested tissues. Strontium can substitute calcium in bioactive materials without adverse local or systemic effects.

Strontium-loaded titanium-15molybdenum surface improves physicochemical and biological propertiesin vitro.

The titanium alloy composition and microdesign affect the dynamic interplay between the bone cells and titanium surface in the osseointegration process. The current study aimed to evaluate the surface physicochemical properties, electrochemical stability, and the metabolic response of the MC3T3-E1 cells (pre-osteoblast cell line) cultured onto titanium-15molybdenum (Ti-15Mo) discs treated with phosphoric acid (H3PO4) and sodium hydroxide (NaOH) and/or strontium-loading by the hydrothermal method. The x-ray dispersive energy spectroscopy (EDS) and x-ray diffraction (XRD) analysis showed no trace of impurities and the possible formation of hydrated strontium oxide (H2O2Sr), respectively. The confocal laser microscopy (CLSM) analysis indicated that titanium samples treated with strontium (Sr) showed greater surface roughness. The acid/alkali treatment prior to the hydrothermal Sr deposition improved the surface free energy and resistance to corrosion of the Ti-15Mo alloy. The acid/alkali treatment also provided greater retention of the Sr particles on the Ti-15Mo surfaces accordingly with inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. The AlamarBlue and fluorescence analysis indicated noncytotoxic effects against the MC3T3-E1 cells, which allowed cells' adhesion and proliferation, with greater cells' spreading in the Sr-loaded Ti-15Mo samples. These findings suggest that Sr deposition by the hydrothermal method has the potential to enhance the physicochemical properties of the Ti-15Mo previously etched with H3PO4and NaOH, and also improve the initial events related to cell-mediated bone deposition.

Fabrication and characterization of a bioactive polymethylmethacrylate-based porous cement loaded with strontium/calcium apatite nanoparticles.

Polymethylmethacrylate (PMMA)-based cements are used for bone reparation due to their biocompatibility, suitable mechanical properties, and mouldability. However, these materials suffer from high exothermic polymerization and poor bioactivity, which can cause the formation of fibrous tissue around the implant and aseptic loosening. Herein, we tackled these problems by adding Sr2+ -substituted hydroxyapatite nanoparticles (NPs) and a porogenic compound to the formulations, thus creating a microenvironment suitable for the proliferation of osteoblasts. The NPs resembled the structure of the bone's apatite and enabled the controlled release of Sr2+ . Trends in the X-ray patterns and infrared spectra confirmed that Sr2+ replaced Ca2+ in the whole composition range of the NPs. The inclusion of an effervescent additive reduced the polymerization temperature and lead to the formation of highly porous cement exhibiting mechanical properties comparable to the trabecular bone. The formation of an opened and interconnected matrix allowed osteoblasts to penetrate the cement structure. Most importantly, the gas formation confined the NPs at the surface of the pores, guaranteeing the controlled delivery of Sr2+ within a concentration sufficient to maintain osteoblast viability. Additionally, the cement was able to form apatite when immersed into simulated body fluids, further increasing its bioactivity. Therefore, we offer a formulation of PMMA cement with improved in vitro performance supported by enhanced bioactivity, increased osteoblast viability and deposition of mineralized matrix assigned to the loading with Sr2+ -substituted hydroxyapatite NPs and the creation of an interconnected porous structure. Altogether, our results hold promise for enhanced bone reparation guided by PMMA cements.

Effect of bioactive glasses containing strontium and potassium on dentin permeability.

Dentin hypersensitivity (DH) is characterized by pain caused by an external stimulus on exposed dentin. Different therapeutic approaches have been proposed to mitigate this problem; however, none of them provide permanent pain relief. In this study, we synthesized and characterized experimental bioactive glasses containing 3.07 mol% SrO or 3.36 mol% K2 O (both equivalent to 5 wt% in the glass), and evaluated their effect on dentin permeability to verify their potential to treat DH. The experimental materials were characterized by field-emission scanning electron microscopy, Fourier transform infrared spectroscopy, micro-Raman spectroscopy, and X-ray diffraction to confirm the respective structures and chemical compositions. The reduction in the hydraulic conductance of dentin was evaluated at the three stages: minimum permeability; maximum permeability (24% ethylenediaminetetraacetic acid [EDTA] treatment); and final dentin permeability after treatment with the bioactive glasses. They all promoted a reduction in dentin permeability, with a significant difference for each sample and posttreatment group. Also, a significant reduction in dentin permeability was observed even after a simulated toothbrushing test, demonstrating effective action of these materials against DH. Besides, incorporating 3.07 mol% SrO was a positive factor. Therefore, strontium's desensitizing and re-mineralizing properties can be further exploited in bioactive glasses to promote a synergistic effect to treat DH.

Enamel erosion control by strontium-containing TiO2- and/or MgO-doped phosphate bioactive glass.

OBJECTIVES: To evaluate the effect of strontium-containing titanium- and/or magnesium-doped phosphate bioactive glass on the control of dental erosion. MATERIALS AND METHODS: Fifty fragments of human enamel were divided into five groups: negative control, 45S5 bioglass, strontium-containing Ti-doped phosphate bioactive glass (PBG-Ti), strontium-containing Mg-doped phosphate bioactive glass (PBG-Mg), and strontium-containing Ti- and Mg-doped phosphate bioactive glass (PBG-TiMg). The specimens underwent cycles of erosive challenge twice daily for 5 days with 1 mL of citric acid for 2 min followed by 1 mL of the suspension with bioactive substances for 3 min. After the cycles, profilometry, roughness and microhardness testing, and scanning electron microscopy (SEM) were performed. The following statistical tests were used: one-way ANOVA (profile, roughness, and surface microhardness (%VMS) data variation), Tukey's HSD (%VMS), Games-Howell test (profilometry), Student's t test (roughness), and Pearson's correlation between the variables. RESULTS: The lower loss of enamel surface and lower %VMS was observed in the PBG-Mg and PBG-TiMg groups, and only the PBG-Mg group showed similar roughness between baseline and eroded areas (p > 0.05). On SEM micrographs, PBG-Ti and PBG-Mg groups showed lower apparent demineralization. CONCLUSION: All bioactive materials protected the enamel against erosion. However, strontium-containing phosphate bioactive glasses showed lower enamel loss, and the presence of Mg in these bioactive glasses provided a greater protective effect. CLINICAL RELEVANCE: Experimental strontium-containing phosphate bioactive glasses are effective in controlling enamel erosion. The results obtained in this study will guide the development of new dental products.

Combination of strontium chloride and photobiomodulation in the control of tooth sensitivity post-bleaching: A split-mouth randomized clinical trial.

OBJECTIVE: This split-mouth randomized controlled clinical trial assessed the effect of 10% strontium chloride in combination with photobiomodulation (PBM) for the control of tooth sensitivity (TS) post-bleaching. METHODS: The upper/lower, right and left quadrants of fifty volunteers were randomized and allocated to four groups (n = 25): PLACEBO-placebo gel + simulation of PBM; Placebo + PBM; STRONTIUM-10% strontium chloride + simulation of PBM; and PBM + STRONTIUM-10% strontium chloride + PBM. All groups received tooth bleaching treatment with 35% hydrogen peroxide. For the PBM treatment, the laser tip was positioned in the apical and cervical regions of the teeth bleached in the respective hemi-arch. The laser system was operated in continuous mode, using 1.7 J of energy. A dose of 60 J/cm2 was applied to each point for 16 seconds under 808 nm near-infrared light (100mW of power), with a point area of 0.028 cm2. TS was assessed during a 21-day follow-up, using the modified visual analogue scale. RESULTS: In the intragroup assessment, the Friedman test indicated that PBM + STRONTIUM promoted the greatest reduction in TS after the second week of treatment (p ≤ 0.05). The Wilcoxon-Mann-Whitney test indicated that the groups Placebo + PBM, STRONTIUM, and STRONTIUM + PBM did not differ statistically (p ≥ 0.05) in the first and third weeks of treatment The group PLACEBO exhibited the greatest TS in the first three days after each bleaching session. CONCLUSION: The combination of 10% strontium chloride with PBM was effective in reducing post-bleaching TS; however, the combination of 10% strontium chloride with PBM was effective in reducing post-bleaching TS; however, it did not differ from the individual use of Placebo + PBM or STRONTIUM groups assessed after 21 days of follow-up.

Synthesis and characterization of poly(vinyl alcohol)/chondroitin sulfate composite hydrogels containing strontium-doped hydroxyapatite as promising biomaterials.

Novel poly(vinyl alcohol)/chondroitin sulfate (PVA/CS) composite hydrogels containing hydroxyapatite (HA) or Sr-doped HA (HASr) particles were synthesized by a freeze/thaw method and characterized aiming towards biomedical applications. HA and HASr were synthesized by a wet-precipitation method and added to the composite hydrogels in fractions up to 15 wt%. Physical-chemical characterizations of particles and hydrogels included scanning electron microscopy, energy-dispersive spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetry, porosity, compressive strength/elastic modulus, swelling degree, and cell viability. Particles were irregular in shape and appeared to have narrow size variation. The thermal behavior of composite hydrogels was altered compared to the control (bare) hydrogel. All hydrogels exhibited high porosity. HA/HASr particles reduced total porosity without reducing pore size. The mechanical strength was improved as the fraction of HA or HASr was increased. HASr particles led to a faster water uptake but did not interfere with the total hydrogel swelling capacity. In cell viability essay, increased cell growth (above 120%) was observed in all groups including the control hydrogel, suggesting a bioactive effect. In conclusion, PVA/CS hydrogels containing HA or HASr particles were successfully synthesized and showed promising morphological, mechanical, and swelling properties, which are particularly required for scaffolding.

Strontium Calcium Phosphate Nanotubes as Bioinspired Building Blocks for Bone Regeneration.

Calcium phosphate (CaP)-based ceramics are the most investigated materials for bone repairing and regeneration. However, the clinical performance of commercial ceramics is still far from that of the native tissue, which remains as the gold standard. Thus, reproducing the structural architecture and composition of bone matrix should trigger biomimetic response in synthetic materials. Here, we propose an innovative strategy based on the use of track-etched membranes as physical confinement to produce collagen-free strontium-substituted CaP nanotubes that tend to mimic the building block of bone, i.e., the mineralized collagen fibrils. A combination of high-resolution microscopic and spectroscopic techniques revealed the underlying mechanisms driving the nanotube formation. Under confinement, poorly crystalline apatite platelets assembled into tubes that resembled the mineralized collagen fibrils in terms of diameter and structure of bioapatite. Furthermore, the synergetic effect of Sr2+ and confinement gave rise to the stabilization of amorphous strontium CaP nanotubes. The nanotubes were tested in long-term culture of osteoblasts, supporting their maturation and mineralization without eliciting any cytotoxicity. Sr2+ released from the particles reduced the differentiation and activity of osteoclasts in a Sr2+ concentration-dependent manner. Their bioactivity was evaluated in a serum-like solution, showing that the particles spatially guided the biomimetic remineralization. Further, these effects were achieved at strikingly low concentrations of Sr2+ that is crucial to avoid side effects. Overall, these results open simple and promising pathways to develop a new generation of CaP multifunctional ceramics that are active in tissue regeneration and able to simultaneously induce biomimetic remineralization and control the imbalanced osteoclast activity responsible for bone density loss.

In vitro effects of the co-release of icariin and strontium from bioactive glass submicron spheres on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells.

Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Typical osteoporosis fracture treatments, such as bisphosphonates and hormone replacement, present important challenges because of their low bioavailability on the site of action. Options to overcome this issue are systems for the local release of therapeutic agents such as bioactive glasses containing therapeutic molecules and ions. These agents are released during the dissolution process, combining the drugs and ion therapeutic effects for osteoporosis treatment. Among the therapeutic agents that can be applied for bone repair are strontium (Sr) ion and phytopharmaceutical icariin, which have shown potential to promote healthy bone marrow stem cells osteogenic differentiation, increase bone formation and prevent bone loss. Submicron Sr-containing bioactive glass mesoporous spheres with sustained ion release capacity were obtained. Icariin was successfully incorporated into the particles, and the glass composition influenced the icariin incorporation efficiency and release rates. In this work, for the first time, Sr and icariin were incorporated into bioactive glass submicron mesoporous spheres and the in vitro effects of the therapeutic agents release were evaluated on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells, and results showed an improvement on the reduced differentiation potential.