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Development of a new calcium phosphate cement that contains sodium calcium phosphate.

A cement powder consisting of sodium calcium phosphate, Na3Ca6(PO4)5, in addition to tetracalcium phosphate and beta-tricalcium phosphate was prepared by pulverizing blocks of 4 wt% sodium-, 11 wt% carbonate-containing apatite samples that were heated at 1700 degrees C for 5 h. When mixed with 30 wt% malic acid or citric acid at a powder liquid ratio of 3:1, the cement set in 3 or 7 min at room temperature with compressive strength being around 52 or 27 MPa. In HeLa-cell cultures, the cement mixed with malic acid was less cytotoxic than the cement mixed with citric acid, which was far less cytotoxic than a commercial carboxylate cement used as a negative control, suggesting malic acid to be superior to citric acid as a liquid in this regard. Similar findings were also obtained with osteoclasts, of which culture experiments clearly suggested that the number of osteoclasts on the cement mixed with malic acid was significantly greater than that on the cement mixed with citric acid. Since osteoclastic response to substrates could be used as a maker in evaluating their bioresorbability associated with osteoclasts, the above finding may suggest that the cement that is to be mixed with malic acid would be more useful as bone substitutes.

Animals↗

[Evaluation of the effect of ligation of the inferior thyroid arteries during non-radical thyroidectomy in simple goiter on selected parameters of calcium-phosphate metabolism in the body].

The aim of the paper was to evaluate the effect of inferior thyroid arteries ligation during the incomplete excision of the thyroid gland in patients with simple goitre, exerted on selected parameters of phosphate-calcium balance in the organism as compared with a group of patients, in whom no inferior thyroid arteries were ligated. The study material comprised 84 patients with simple goitre, free of other diseases. The evaluation covered the following parameters of the phosphate-calcium balance in the organism, namely: the concentration of total calcium, protein, dialyzing calcium, inorganic phosphate as well as immunoreactive parathyroid hormone. The study was performed three times: prior to operative procedure, directly after the operative procedure, and three months after the procedure. It has been shown that there are slight, but statistically significant, differences in the behaviour involving the concentration of total and dialyzing calcium as well as IRPTH in serum, depending on the applied operative technique. Directly after the procedure the changes affecting the studied parameters were more pronounced in patients with ligated inferior thyroid arteries. Three months after the operative procedure the mean concentration of IRPTH, total and dialyzing calcium was somewhat higher in patients, whose inferior thyroid arteries were ligated, than in patients, in whom the arteries were not ligated. The described changes were of subclinical character.

Adolescent↗

Aluminium phosphate but not calcium phosphate stimulates the specific IgE response in guinea pigs to tetanus toxoid.

The ability of aluminium phosphate and calcium phosphate to stimulate the synthesis of tetanus toxoid-specific anaphilactic and antitoxic antibodies is compared. The observed differences in the kinetics of IgG1a, IgG1b and antitoxines are quantitative--titres after application of aluminium phosphate are higher. Booster immunization with aluminium but not calcium phosphate-adsorbed toxoid leads to a prolonged synthesis of specific IgE. It is hypothesized that the regular application of aluminium compound-containing vaccines on the entire population could be one of the factors leading to the observed increase of allergic diseases.

Aluminum↗

The properties of biomimetically processed calcium phosphate on bioactive ceramics and their response on bone cells.

This study looks for grounds to alter the chemical composition (phosphate, calcium, silica and carbonate), dissolution properties, structure and nanotopography of the biomimetically processed surfaces on bioactive ceramics to optimize their shown ability to influence bone cell behaviour and production of new bone. In the bone environment desirable characteristic of these materials is their ability to be remodeled by natural osteoclastic resorption. Different silica and carbonate containing calcium phosphate layers were prepared on bioactive glasses 9 (S53P4) and 1-98 (S53P2) and sol-gel processed pure silica SiO2 in C- and R-SBF (conventional and revised simulated body fluid) for varying periods of time. It was shown that in R-SBF the CaP layer formed faster compared to C-SBF. The CaP layer in the R-SBF contained more carbonate (CO3(2-)) compared to that formed with the same immersion time in C-SBF. The CaP so formed in R-SBF with faster precipitation is more amorphous than the bonelike HCA formed in C-SBF. The results indicate that the most suitable surface for both osteoblasts and osteoclasts was found to be an amorphous CaP having mesoporous nanotopography and proper dissolution rate of calcium and silica.

Animals↗

Calcium phosphate: an alternative calcium compound for dietary prevention of colon cancer? A study on intestinal and faecal parameters in healthy volunteers.

In an effort to reduce the risk of colorectal cancer development, oral calcium carbonate supplementation has been used in previous studies for the precipitation of cytotoxic bile acids and fatty acids. In human intervention trials its effect on mucosal hyperproliferation in the colorectum has not always been satisfactory. Because the complexation of calcium and bile acids requires the formation of calcium phosphate, we performed an intervention study in 14 healthy volunteers, giving them 1,500 mg calcium as Ca3(PO4)2 for 1 week. The effects of tricalcium phosphate on luminal and faecal parameters of cytolytic activity were evaluated before, during, and after calcium phosphate supplementation. The cytolytic activity of faecal water and intestinal alkaline phosphatase activity in faecal water were not affected by supplemental calcium phosphate. In duodenal bile, the proportion of cholic acid tended to increase, whereas that of chenodeoxycholic acid tended to decrease during calcium phosphate supplementation. Neither concentrations of total and individual faecal bile acids, nor that of faecal fat were affected during calcium phosphate supplementation. It is suggested that, although phosphate is involved in bile acid precipitation, phosphate competes for calcium in the binding of fatty acids. This might possibly explain the unchanged cytolytic potency of faecal water, and therefore does not make tricalcium phosphate a suitable calcium compound for dietary intervention.

Adult↗

[Calcitonin, calcium lactate-gluconate + potassium phosphate, calcium phosphate: changes induced in the biology of the patient with multiple fractures].

The effects of multiple injuries on the principle aspects of bone physiology are reviewed from the literature. In a clinical trial involving 14 patients with multiple fractures excluding cranial injuries, 5 were given porcine Calcitonin, two calcium gluconate-lactate with added potassium phosphate, and two calcium phosphate. Five patients acted as controls. The parameters under study were modified to varying degrees by the different substances. It was found that Calcitonin had no effect whatsoever on the healing of bone which remained virtually unaltered by the other compounds under trial.

Alkaline Phosphatase↗

Chloride- and alkali-containing calcium phosphates as basic materials to prepare calcium phosphate cements.

Combinations of an alkali-containing calcium phosphate-like rhenanite, sodium whitlockite or calcium potassium phosphate and a chloride-containing calcium phosphate-like spodiosite or chloroapatite with or without additions of other calcium phosphates like monocalcium phosphate monohydrate, dicalcium phosphate or dicalcium phosphate dihydrate were made and mixed with water into pastes. The setting time of these pastes was determined. After soaking for a day in Ringer's solution at 37 degrees C the compressive strength and the diametral tensile strength were determined. Two of the combinations tried in this study resulted in the formation of cements at room temperature. One cement was of the type dicalcium phosphate, whereas the other gave octocalcium phosphate as the solid reaction product. The byproducts formed were an aqueous solution of NaCl and one of K2HPO4, respectively. Applications for bone repair and augmentation are envisaged.

Alkalies↗

Short-term implantation effects of a DCPD-based calcium phosphate cement.

Calcium phosphate cements can be handled in paste form and set in a wet medium after precipitation of calcium phosphate crystals in the implantation site. Depending on the products entering into the chemical reaction leading to the precipitation of calcium phosphates, different phases can be obtained with different mechanical properties, setting times and injectability. We tested a cement composed of a powder, containing beta-tricalcium phosphate (beta-TCP) and sodium pyrophosphate mixed with a solution of phosphoric and sulphuric acids. The cement set under a dicalcium phosphate dihydrate (DCPD)-based matrix containing beta-TCP particles. This was injected with a syringe into a defect drilled in rabbit condyles, the control being an identical defect left empty in the opposite condyle. The condyles were analysed histologically 2, 6 and 18 weeks after implantation. After injection into the bone defect the cement set and formed a porous calcium phosphate structure. Two different calcium phosphate phases with different solubility rates could be identified by scanning electron microscopy (SEM) observation. The less-soluble fragments could be degraded by cell phagocytosis in cell compartments of low pH or integrated in the newly formed bone matrix. The degradation rate of the material was relatively high but compatible with the ingrowth of bone trabeculae within the resorbing material. The ossification process was different from the creeping substitution occurring at the ceramic contact. Bone did not form directly at the cement surface following the differentiation of osteoblasts at the material surface. The trabeculae came to the material surface from the edges of the implantation site. Bone formation in the implantation site was significantly higher than in the control region during the first week of implantation. In conclusion, this material set in situ was well tolerated, inducing a mild foreign-body reaction, which did not impair its replacement by newly formed bone within a few weeks.

Animals↗

Optimization of calcium phosphate transfection for bovine chromaffin cells: relationship to calcium phosphate precipitate formation.

Optimal conditions for formation of calcium phosphate-DNA precipitates and for chromaffin cell transfection by the calcium phosphate method were examined. A relationship was observed between turbidity of calcium phosphate solutions and the ability of calcium phosphate-DNA mixtures to give efficient transfection of bovine chromaffin cells. Under optimal conditions up to 35% of chromaffin cells in cultures transfected with plasmid DNA encoding human proenkephalin or Escherichia coli beta-galactosidase expressed the respective proteins. Important factors for transfection were the pH (6.95) and buffer employed for calcium phosphate-DNA precipitate formation, the amount and type of DNA, and the absence of serum in the cultures. Additionally, phosphate and calcium concentrations in the culture medium during incubation of cells with DNA are critical. Optimal conditions for transfection of chromaffin cells were also useful for transfection of clonal BSC-40 cells, an African green monkey kidney cell line. These results suggest that the optimal conditions described here for chromaffin cells may have broad applicability to other cell types. In addition, the results suggest that it is possible to optimize the solutions used for transfection conditions by monitoring calcium phosphate formation.

Adrenal Medulla↗

Biomechanical characterization of a biodegradable calcium phosphate hydraulic cement: a comparison with porous biphasic calcium phosphate ceramics.

Biomechanical properties of a biodegradable calcium phosphate hydraulic cement (CPHC) were tested with rabbits. The cement was composed of beta-tricalcium phosphate (beta-TCP), monocalcium phosphate monohydrate (MCPM), and calcium sulfate hemihydrate (CSH), beta-TCP-MCPM-CSH cement. Cylinders of 4.7 mm in diameter and 10 mm in length were put into bone cavities created in the distal epiphysis of femurs in rabbits. Cylinders of the same size of porous biphasic calcium phosphate ceramics (BCPC, 75% hydroxyapatite and 25% beta-TCP) were implanted as references. Two, 4, 12, and 16 weeks after the operation, the rabbits were sacrificed. Histomorphometry showed that the cement was resorbed, leaving only 7.67 +/- 1.81% of bone cavity after 12 weeks. Newly formed bone occupied 34.59 +/- 4.00% of the cavity. Cylindrical bone-material composites were cut out with a small dental burr. Compressive force was applied to the specimens and compressive strength, elastic modulus, and toughness were calculated. The same tests were performed on cylinders of normal bone from the same site, which served as controls. The compressive strength and the toughness of the cement-bone composite were higher than those of normal bone and porous ceramics 12 weeks after the operation (p < 0.05). At 16 weeks the compressive strength and the toughness returned to the normal bone values. The elastic modulus of the porous ceramic-bone composite was higher than the normal bone at 4, 12, and 16 weeks after surgery (p < 0.05). We found that the beta-TCP-MCPM-CSH cement is replaced by new bone and that the cement-new bone composite has similar or better mechanical properties than normal bone within 16 weeks. This study suggests the usefulness of a particular cement for filling bone defects or for temporary fixation of orthopedic implants.

Animals↗

Structure and adsorption properties of commercial calcium phosphate adjuvant.

Calcium phosphate adjuvant is a commercially available vaccine adjuvant that potentiates the immune response to antigens. Although its name suggests that it is Ca3(PO4)2, X-ray diffraction, FTIR spectroscopy, thermal analysis and the Ca/P molar ratio identify commercial calcium phosphate adjuvant as non-stoichiometric hydroxyapatite, Ca10-x (HPO4)x (PO4)6-x (OH)2-x, where x varies from 0 to 2. The surface charge is pH-dependent (point of zero charge = 5.5). Consequently, commercial calcium phosphate adjuvant exhibits a negative surface charge at physiological pH and electrostatically adsorbs positively charged antigens. The presence of hydroxyls allows calcium phosphate adjuvant to adsorb phosphorylated antigens by ligand exchange with surface hydroxyls.

Adjuvants, Immunologic↗

Physical properties and self-setting mechanism of calcium phosphate cements from calcium bis-dihydrogenophosphate monohydrate and calcium oxide.

An apatitic calcium phosphate cement was developed from calcium bis-dihydro-genophosphate monohydrate (or monocalcium phosphate monohydrate, MCPM) and calcium oxide (CaO). The powder had a Ca/P molar ratio of 1.67, and the liquid was either pure water or 0.25 M-1 M sodium phosphate buffer, pH 7.4. The influence of the powder-to-liquid (P/L) ratio on the setting time and the mechanical strength were studied. The best results were obtained for the 1 M phosphate buffer with a P/L ratio of 1.53; the setting time was 7 min and the compressive strength was 25 MPa after 24 h and 33 MPa after 11 d. The mechanism and kinetics of the setting reaction were investigated by X-ray diffraction, differential scanning calorimetry, 31P magic angle spinning-nuclear magnetic resonance and infrared spectrometry. The setting reaction was found to be biphasic: in the first step, during the mixing time, MCPM reacted with CaO immediately to give calcium hydrogenophosphate dihydrate (or dicalcium phosphate dihydrate, DCPD) which, in the second step, reacted more slowly with the remaining CaO to give hydroxyapatite. The conversion of the starting materials to hydroxyapatite was complete within 24 h when the liquid was water, but was slower and incomplete with the phosphate buffers. Of the starting materials, 30% remained after 3 d.

Journal Article↗

Modulation of porosity in apatitic cements by the use of alpha-tricalcium phosphate-calcium sulphate dihydrate mixtures.

Calcium phosphate bone cements are injectable biomaterials that are being used in dental and orthopaedic applications through minimally invasive surgery techniques. Nowadays, apatitic bone cements based on alpha-tricalcium phosphate (alpha-TCP) are of special interest due to their self-setting behaviour when mixed with an aqueous liquid phase. In this study, a new method to improve osteointegration of alpha-TCP-based cements is presented. This method consists in the modification of the cement's powder phase with different amounts of calcium sulphate dihydrate (CSD). The resulting hardening properties of the new biphasic cements are a combination between the progressive hardening due to the main alpha-TCP reactant and the progressive dissolution of the CSD phase, which render a porous material. It was observed that the maximum compressive strength of Biocement-H (45 MPa) decreased as the amount of CSD increased in the cement powder mixture ( approximately 30 MPa for 25 wt% of CSD). It was also observed that after complete dissolution of the CSD phase a porous apatitic structure appears with a mechanical compressive strength suitable for cancellous bone applications (10 MPa).

Apatites↗