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.
Tissue Scaffolds/chemistry* ; Biocompatible Materials ; Strontium/pharmacology* ; Ions ; Hydrogen-Ion Concentration ; Tissue Engineering/methods* ; Porosity

OBJECTIVE: To evaluate the biocompatibility and osteogenic effect of new calcium phosphate cement (CPC) in vivo and to provide experimental basis for its further clinical application. METHODS: Thirty New Zealand white rabbits were randomly divided into four groups: CPC group, CPC+Bio-Oss group, Bio-Oss group and blank control group. Bone defect models of 6 mm in diameter and 7 mm in depth were made on the lateral condyle of bilateral hind legs of the rabbits. CPC, Bio-Oss and CPC+Bio-Oss mixture were implanted into the bone defect according to the group, and the mass ratio of CPC and Bio-Oss was 4 ∶ 1. The experimental animals were sacrificed the 4th, 12th and 24th week after operation. The tissue around the bone defect was taken for histological evaluation by H&E staining. Bone ingrowth fraction (BIF) was calculated. The expression of BMP-2 and COL-Ⅰ was detected by immunohis- tochemical staining by calculating the mean optical density (MOD) of the positive area the 4th week after operation, and the bone healing of each group was evaluated at different time points. The measurement data were analyzed by one-way ANOVA and LSD test was used for multiple comparison of the differences between the means by SPSS 19.0. P < 0.05 was considered to be statistically significant. RESULTS: The results of H&E staining showed that the BIF values of CPC group, CPC + Bio-Oss group and Bio-Oss group were significantly higher than those of blank control group at the same time point (P < 0.01). The BIF values of CPC group were lower than those of Bio-Oss group and CPC + Bio-Oss group (P < 0.01). There was no significant difference between CPC + Bio-Oss group and Bio-Oss group. Immunohistochemical staining showed that the MOD values of BMP-2 and COL-Ⅰ in CPC group were higher than those in blank control group, but lower than those in Bio-Oss group and CPC+Bio-Oss group (P < 0.01). There was no significant difference between BMP-2 and COL-Ⅰ in CPC+Bio-Oss group and Bio-Oss group. CONCLUSION The new calcium phosphate cement has good biocompatibility and can promote early osteogenesis with stable and long-term effect.
Animals ; Bone Cements ; Calcium ; Calcium Phosphates ; Osteogenesis ; Rabbits ; Strontium

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.
Bone Resorption ; Humans ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Strontium

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.
Autografts ; Beauty ; Cell Line ; Cell Lineage ; Durapatite ; Endothelium ; Flow Cytometry ; Human Umbilical Vein Endothelial Cells ; Mesenchymal Stromal Cells ; Methods ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Nanocomposites ; Nanotubes ; Osteoblasts ; Osteogenesis ; Polymers ; Real-Time Polymerase Chain Reaction ; Regenerative Medicine ; Silicon Dioxide ; Strontium ; Wharton Jelly

BACKGROUND: Nowadays, production of nanocomposite scaffolds based on natural biopolymer, bioceramic, and metal ions is a growing field of research due to the potential for bone tissue engineering applications. METHODS: In this study, a nanocomposite scaffold for bone tissue engineering was successfully prepared using collagen (COL), beta-tricalcium phosphate (β-TCP) and strontium oxide (SrO). A composition of β-TCP (4.9 g) was prepared by doping with SrO (0.05 g). Biocompatible porous nanocomposite scaffolds were prepared by freeze-drying in different formulations [COL, COL/β-TCP (1:2 w/w), and COL/β-TCP-Sr (1:2 w/w)] to be used as a provisional matrix or scaffold for bone tissue engineering. The nanoparticles were characterized by X-ray diffraction, Fourier transforms infrared spectroscopy and energy dispersive spectroscopy. Moreover, the prepared scaffolds were characterized by physicochemical properties, such as porosity, swelling ratio, biodegradation, mechanical properties, and biomineralization. RESULTS: All the scaffolds had a microporous structure with high porosity (~ 95–99%) and appropriate pore size (100–200 µm). COL/β-TCP-Sr scaffolds had the compressive modulus (213.44 ± 0.47 kPa) higher than that of COL/β-TCP (33.14 ± 1.77 kPa). In vitro cytocompatibility, cell attachment and alkaline phosphatase (ALP) activity studies performed using rat bone marrow mesenchymal stem cells. Addition of β-TCP-Sr to collagen scaffolds increased ALP activity by 1.33–1.79 and 2.92–4.57 folds after 7 and 14 days of culture, respectively. CONCLUSION: In summary, it was found that the incorporation of Sr into the collagen-β-TCP scaffolds has a great potential for bone tissue engineering applications.
Alkaline Phosphatase ; Animals ; Biopolymers ; Bone and Bones ; Bone Marrow ; Collagen ; Fourier Analysis ; Freeze Drying ; In Vitro Techniques ; Ions ; Mesenchymal Stromal Cells ; Nanocomposites ; Nanoparticles ; Porosity ; Rats ; Spectrum Analysis ; Strontium ; X-Ray Diffraction

A magnetic metal organic framework (MMOF) was synthesized and used to separate Sr2+ in aqueous solution. The shape and structure of prepared Fe3O4@UiO-66-NH2 were characterized, and the absorbed concentration of strontium was determined through inductively coupled plasma mass spectrometry. The results indicated that Fe3O4 and UiO-66-NH2 combined through chemical bonding. The experimental adsorption results for separation of Sr2+ in aqueous solution indicated that the adsorption of Sr2+ to Fe3O4@UiO-66-NH2 increased drastically from pH 11 to pH 13. The adsorption isotherm model indicated that the adsorption of Sr2+ conformed to the Freundlich isotherm model (R2 = 0.9919). The MMOF thus inherited the superior qualities of magnetic composites and metal organic frameworks, and can easily be separated under an external magnetic field. This MMOF thus has potential applications as a magnetic adsorbent for low level radionuclide 90Sr.
Adsorption ; Ferrosoferric Oxide ; chemistry ; Hydrogen-Ion Concentration ; Metal-Organic Frameworks ; chemical synthesis ; chemistry ; Models, Theoretical ; Nanoparticles ; chemistry ; Strontium ; analysis ; Surface Properties ; Water Pollutants, Radioactive ; analysis ; Water Purification ; methods

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
Bone Density Conservation Agents/therapeutic use* ; Bone Neoplasms/secondary* ; Denosumab/therapeutic use* ; Diphosphonates/therapeutic use* ; Endothelins/antagonists & inhibitors* ; Humans ; Male ; Prostatic Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Radioisotopes/therapeutic use* ; Radiopharmaceuticals/therapeutic use* ; Radium/therapeutic use* ; Samarium/therapeutic use* ; Strontium Radioisotopes/therapeutic use*

OBJECTIVETo prepare a novel strontium-containing calcium sulfate and assess its and biocompatibility.

METHODSA novel strontium-containing α-calcium sulfate hemihydrate (Sr-caS) bone substitute as prepared with hydrothermal reaction and examined for X-ray diffraction (XRD), Fourier transform infrared (FTIR) and thermogravimetric differential scanning calorimetric (TG-DSC) patterns. The biocompatibility of the material was evaluated by in vitro cytotoxicity test in L-929 cells, hemolysis test of blood, and in vivo implantation test in SD rats.

RESULTSThe XRD spectra of the prepared Sr-CaS powder highlighted 3 strong characteristic peaks of α-CaSO4 at 14.63°, 25.72° and 29.80° with a strontium-specific peak at 24.78°. The FTIR patterns of Sr-CaS resembled those of CaS. TG-DSC results showed that the material contained a non-evaporable water content of 6.03%. In vitro cytotoxicity test in L-929 cells suggested that the material had a class 1 cytotoxicity, and the hemolysis rate of its aqueous extract was 4.3%. The material implanted in the muscular tissues of SD rats maintained a steady state in the surrounding tissues.

CONCLUSIONThis strontium-containing calcium sulfate material we prepared shows an excellent biocompatibility for potential use as a novel artificial bone material.

Animals ; Biocompatible Materials ; chemistry ; Bone Substitutes ; chemistry ; Calcium Sulfate ; chemistry ; Cell Line ; Mice ; Microscopy, Electron, Scanning ; Prostheses and Implants ; Rats ; Rats, Sprague-Dawley ; Spectroscopy, Fourier Transform Infrared ; Strontium ; chemistry ; X-Ray Diffraction

OBJECTIVES: This study aimed to analyze the mineral composition of naturally- and artificially-produced caries-affected root dentin and to determine the elemental incorporation of resin-modified glass ionomer (RMGI) into the demineralized dentin. MATERIALS AND METHODS: Box-formed cavities were prepared on buccal and lingual root surfaces of sound human premolars (n = 15). One cavity was exposed to a microbial caries model using a strain of Streptococcus mutans. The other cavity was subjected to a chemical model under pH cycling. Premolars and molars with root surface caries were used as a natural caries model (n = 15). Outer caries lesion was removed using a carbide bur and a hand excavator under a dyeing technique and restored with RMGI (FujiII LC, GC Corp.). The weight percentages of calcium (Ca), phosphate (P), and strontium (Sr) and the widths of demineralized dentin were determined by electron probe microanalysis and compared among the groups using ANOVA and Tukey test (p < 0.05). RESULTS: There was a pattern of demineralization in all models, as visualized with scanning electron microscopy. Artificial models induced greater losses of Ca and P and larger widths of demineralized dentin than did a natural caries model (p < 0.05). Sr was diffused into the demineralized dentin layer from RMGI. CONCLUSIONS: Both microbial and chemical caries models produced similar patterns of mineral composition on the caries-affected dentin. However, the artificial lesions had a relatively larger extent of demineralization than did the natural lesions. RMGI was incorporated into the superficial layer of the caries-affected dentin.
Bicuspid ; Calcium ; Dentin* ; Electron Probe Microanalysis ; Glass ; Hand ; Humans ; Hydrogen-Ion Concentration ; Microscopy, Electron, Scanning ; Miners ; Models, Chemical ; Molar ; Root Caries ; Streptococcus mutans ; Strontium

Metastatic bone disease is a major sequela of several malignancies, such as the prostate, breast, lung, kidney and thyroid. Bone pain is a common symptom in advancing malignancy and often determines the quality of life in the later stages of disease. Management of bone pain from metastasis remains palliative at present. With the improved cancer survival resulting from advances in cancer management, the population of patients seeking relief of bone pain has increased. Radiopharmaceutical therapy offers potential pain relief with minimal adverse effects. This is a case report on the clinical utility of strontium-89 chloride for the palliation of bone pain in metastatic prostate cancer. A 67-year-old male presented with bone pain due to disseminated bone metastases form prostate cancer, most intense in the lower back (Visual Analogue Scale pain score of 8). Strontium-89 chloride was administered intravenously at a dose of 148 MBq (4mCi). There was a transient, moderate, tolerable pain flare (Visual Analogue Scale pain score of 4) within the first week of treatment, which was relieved by oral opioid analgesics. He was pain-free thereafter (Visual Analogue Scale pain score of 0). Reversible bone marrow suppression was also observed a few weeks after the treatment.

Human ; Male ; Aged ; .analgesics, Opioid ; Radiopharmaceuticals ; Strontium Chloride ; Strontium ; Thyroid Gland ; Bone Marrow ; Quality Of Life ; Visual Analog Scale ; Prostatic Neoplasms ; Bone Neoplasms ; Pain Management