Antimicrobial properties and dentin bonding strength of magnesium phosphate cements

The main objective of this work was to assess the antimicrobial properties and the dentin-bonding strength of novel magnesium phosphate cements (MPC). Three formulations of MPC, consisting of magnesium oxide and a phosphate salt, NH₄H₂PO₄, NaH₂PO₄ or a mixture of both, were evaluated. As a result of the setting reaction, MPC transformed into either struvite (MgNH₄PO₄·6H₂O) when NH₄H₂PO₄ was used or an amorphous magnesium sodium phosphate when NaH₂PO₄ was used. The MPC had appropriate setting times for hard tissue applications, high early compressive strengths and higher strength of bonding to dentin than commercial mineral trioxide aggregate cement. Bacteriological studies were performed with fresh and aged cements against three bacterial strains, Escherichia coli, Pseudomonas aeruginosa (planktonic and in biofilm) and Aggregatibacter actinomycetemcomitans. These bacteria have been associated with infected implants, as well as other frequent hard tissue related infections. Extracts of different compositions of MPC had bactericidal or bacteriostatic properties against the three bacterial strains tested. This was associated mainly with a synergistic effect between the high osmolarity and alkaline pH of the MPC. These intrinsic antimicrobial properties make MPC preferential candidates for applications in dentistry, such as root fillers, pulp capping agents and cavity liners.     

Antimicrobial potency of alkali ion substituted calcium phosphate cements

Potassium and sodium containing nanoapatite cements were produced by the reaction of mechanically activated CaNaPO(4) (CSP), CaKPO(4) (CPP) and Ca(2)KNa(PO(4))(2) (CPCP) with a 2.5% Na(2)HPO(4) solution. The cements exhibited clinically acceptable setting times of approximately 5 min and compressive strengths of 5-10 MPa. The antimicrobial properties of the cements were tested with the agar diffusion test using Streptococcus salvarius, Staphylococcus epidermis and Candida albicans. All types of alkali ion containing cements showed a significantly higher antimicrobial potency with inhibition zones of approx. 4-11 mm than a commercial calcium hydroxide cement which resulted in small inhibition zones around the cement samples of a maximum of 1.5 mm. The antimicrobial properties of all the cements were not found to diminish even after longer incubation times. This behaviour was attributed to the formation of soluble alkaline metal phosphates during setting which increased the pH value in the agar gel around the alkali containing calcium phosphate cement to 8.5-10.7 compared to 6.5-8.0 for the Ca(OH)(2) product. The high antimicrobial potency of alkali-calcium phosphate cements may find an application in dentistry as pulp capping agents, root fillers or cavity liners.     

硅酸钙-磷酸盐复合骨水泥的制备及其性能研究

分别以α-磷酸三钙（α—TCP）、磷酸四钙（TTCP）为基本原料，添加羟基磷灰石（HAP）、磷酸氢钙（DCPD）、碳酸钙（CaCO2）、氧化钙（CaO）等其它辅料，并与一定量的无定形硅酸钙（CaSiO3）进行复合，确定了钙磷比均为1．50的六种骨水泥配方，对其基本性能进行了研究。对固化骨水泥样品进行了Ringer’S模拟液浸泡实验，研究了浸泡液pH值、样品的抗压强度随浸泡时间的变化。结果表明：调和液0．25MK2HPO4／KH2PO4和无定形CaSiO3对骨水泥有促凝作用，缩短骨水泥的终凝时间，其中初凝时间为4～5．5min，终凝时间为18～19．5min；同时添加适量无定形CaSiO3可以显著提高骨水泥的抗压强度，其中添加适量无定形CaSiO3的以α—TCP为主要原料的骨水泥Ringer’s模拟液浸泡两周后抗压强度可达45．3MPa。     

Structural characterization of phosphorylated chitosan and their applications as effective additives of calcium phosphate cements.

Chitosan was phosphorylated by P2O5 in methanesulfonic acid and the product as water-soluble phosphorylated chitosan (P-chitosans) was then characterized by phosphorus elemental analysis, IR and 31P-NMR spectroscopy. Two calcium phosphate cement (CPC) systems, i.e. (1) monocalcium phosphate monohydrate (MCPM) and calcium oxide (CaO) in 1 M phosphate buffer (pH = 7.4) and (2) dicalcium phosphate dihydrate (DCPD) and calcium hydroxide [Ca(OH)2] in 1 M Na2HPO4 solution, were chosen to improve their mechanical properties by the addition of water-soluble P-chitosans with various values for molecular weight, degree of deacetylation (DD) and degree of substitution (DS). The results show that the compressive strength (CS) and Young's modulus of both CPC formulations after setting were obviously increased and setting time was slightly prolonged by adding water-soluble P-chitosan to the liquid phases. When a suitable amount of P-chitosan was used, two improved CPC formulations were obtained with much better mechanical properties while the setting times were not longer than 15 min. The enhancement of compressive strength was due to high Ca2+-binding ability of phosphorylated chitosan, which could tightly bind the newly formed hydroxyapatite (HA) particles together by polymeric chains. It was noted that excessive addition of P-chitosan would lead to slow setting or no setting at all. The hardened CPC samples containing P-chitosan were characterized via X-ray diffraction spectra and scanning electron microscopy. Their leaching experiment was also carried out. The results indicated that P-chitosan-forced calcium phosphate cements have some good characteristics for clinical applications.     

Strontium modified biocements with zero order release kinetics

Strontium-substituted beta-TCP with the general formula Ca((3-x))Sr(x)(PO(4))(2) (0相似文献   

Kinetic study of citric acid influence on calcium phosphate bone cements as water-reducing agent

Most of the research performed on calcium phosphate bone cements (CPBCs) has dealt with the improvement of bone cement formulations for new, demanding bone-filling applications. In particular, the development of injectable bone cements is of real interest for the biomedical community. The aim of this work was to study the effect of citric acid on the injectability and the setting properties of alpha-tricalcium phosphate-based cements. A comparative kinetic study was performed on cements with and without citric acid relating the hardening curves and the hydration rates using a mathematical approach. Citric acid behaved as a fluidificant during the first stages of the cement mixing. The dissolution-precipitation reactions of the alpha-tricalcium phosphate were retarded with the addition of citric acid and the compressive strength at saturation increased. In conclusion, citric acid can behave as a water-reducing admixture.     

Effect of the calcium to phosphate ratio of tetracalcium phosphate on the properties of calcium phosphate bone cement

Six different tetracalcium phosphate (TTCP) products were synthesized by solid state reaction at high temperature by varying the overall calcium to phosphate ratio of the synthesis mixture. The objective was to evaluate the effect of the calcium to phosphate ratio on a TTCP-dicalcium phosphate dihydrate (DCPD) cement. The resulting six TTCP-DCPD cement mixtures were characterized using X-ray diffraction analysis, scanning electron microscopy, and pH measurements. Setting times and compressive strength (CS) were also measured. Using the TTCP product with a Ca/P ratio of 2.0 resulted in low strength values (25.61 MPa) when distilled water was used as the setting liquid, even though conversion to hydroxyapatite was not prevented, as confirmed by X-ray diffraction. The suspected CaO presence in this TTCP may have affected the cohesiveness of the cement mixture but not the cement setting reaction, however no direct evidence of CaO presence was found. Lower Ca/P ratio products yielded cements with CS values ranging from 46.7 MPa for Ca/P ratio of 1.90 to 38.32 MPa for Ca/P ratio of 1.85. When a dilute sodium phosphate solution was used as the setting liquid, CS values were 15.3% lower than those obtained with water as the setting liquid. Setting times ranged from 18 to 22 min when water was the cement liquid and from 7 to 8 min when sodium phosphate solution was used, and the calcium to phosphate ratio did not have a marked effect on this property.     

Physico-chemical-mechanical and in vitro biological properties of calcium phosphate cements with doped amorphous calcium phosphates

Calcium phosphate cements (CPCs) are successfully used as bone substitutes in dentistry and orthopaedic applications. This study investigated the physico-chemical-mechanical properties of and in vitro biological properties (cell response) of CPCs prepared with amorphous calcium carbonate phosphate (ACCP) doped with magnesium (ACCP-Mg), zinc (ACCp-Zn) or fluoride (ACCP-F) ions. The experimental CPC consisted of alpha-TCP, doped ACCP, and MPCM powders as matrix and biphasic calcium phosphate (BCP) granules. X-ray diffraction analysis showed that the matrix converted to apatite with poor crystallinity (reflecting small crystal size) after setting for 24 h, while BCP remained apparently unchanged. Cements with ACCP-F (F-CPC) had shorter setting times and greater compressive strength compared to cements with ACCP-Mg (Mg-CPC) or ACCP-Zn (Zn-CPC). Scanning electron microscopy (SEM) showed that crystals set on Mg-CPC and Zn-CPC were smaller compared to those on F-CPC. The total porosity of Mg-CPC was greater compared to Zn-CPC or F-CPC. Osteoblast-like cells, MC3T3-E1, remained viable and maintained their ability to express alkaline phosphatase in contact with the CPCs with doped ACCPs.     

Phase composition,mechanical performance and in vitro biocompatibility of hydraulic setting calcium magnesium phosphate cement

Brushite (CaHPO₄·2H₂O)-forming calcium phosphate cements are of great interest as bone replacement materials because they are resorbable in physiological conditions. However, their short setting times and low mechanical strengths limit broad clinical application. In this study, we showed that a significant improvement of these properties of brushite cement could be achieved by the use of magnesium-substituted β-tricalcium phosphate with the general formula Mg_xCa_(3–x)(PO₄)₂ with 0 < x < 3 as cement reactants. The incorporation of magnesium ions increased the setting times of cements from 2 min for a magnesium-free matrix to 8–11 min for Mg_2.25Ca_0.75(PO₄)₂ as reactant. At the same time, the compressive strength of set cements was doubled from 19 MPa to more than 40 MPa after 24 h wet storage. Magnesium ions were not only retarding the setting reaction to brushite but were also forming newberyite (MgHPO₄·3H₂O) as a second setting product. The biocompatibility of the material was investigated in vitro using the osteoblast-like cell line MC3T3-E1. A considerable increase of cell proliferation and expression of alkaline phosphatase, indicating an osteoblastic differentiation, could be noticed. Scanning electron microscopy analysis revealed an obvious cell growth on the surface of the scaffolds. Analysis of the culture medium showed minor alterations of pH value within the physiological range. The concentrations of free calcium, magnesium and phosphate ions were altered markedly due to the chemical solubility of the scaffolds. We conclude that the calcium magnesium phosphate (newberyite) cements have a promising potential for their use as bone replacement material since they provide a suitable biocompatibility, an extended workability and improved mechanical performance compared with brushite cements.     

Novel bioactive composite bone cements based on the beta-tricalcium phosphate-monocalcium phosphate monohydrate composite cement system

Bioactive composite bone cements were obtained by incorporation of tricalcium silicate (Ca3SiO5, C3S) into a brushite bone cement composed of beta-tricalcium phosphate [beta-Ca3(PO4)2, beta-TCP] and monocalcium phosphate monohydrate [Ca(H2PO4)2.H2O, MCPM], and the properties of the new cements were studied and compared with pure brushite cement. The results indicated that the injectability, setting time and short- and long-term mechanical strength of the material are higher than those of pure brushite cement, and the compressive strength of the TCP/MCPM/C3S composite paste increased with increasing aging time. Moreover, the TCP/MCPM/C3S specimens showed significantly improved in vitro bioactivity in simulated body fluid and similar degradability in phosphate-buffered saline as compared with brushite cement. Additionally, the reacted TCP/MCPM/C3S paste possesses the ability to stimulate osteoblast proliferation and promote osteoblastic differentiation of the bone marrow stromal cells. The results indicated that the TCP/MCPM/C3S cements may be used as a bioactive material for bone regeneration, and might have significant clinical advantage over the traditional beta-TCP/MCPM brushite cement.     

Effect of added gelatin on the properties of calcium phosphate cement

This study investigates the effect of gelatin on the setting time, compressive strength, phase evolution and microstructure of calcium phosphate cement. The composite cement powder (about 18 wt% gelatin, and 82 wt% alpha-tricalcium phosphate) was prepared from the solid compound obtained by casting a gelatin aqueous solution containing alpha-tricalcium phosphate. 5 wt% of CaHPO(4) x 2H(2)O were added to the powder before mixing with the liquid phase. Two cement formulations were prepared using two different liquid/powder ratios, and their properties compared with those of control samples, prepared without gelatin. The final setting time increases from 10 min to more than 45 min when the L/P ratio increases from 0.3 to 0.4 ml/g. The presence of gelatin accelerates the setting reaction, and improves the mechanical properties of the cements. The compressive strength increases with the setting reaction up to 10.7-14.0 MPa for the gelatin cements, whereas the control samples exhibit much lower values. The improved mechanical properties of the composite cements with respect to the controls can be related to their reduced total porosity and more compact microstructure.     

Effects of neutral sodium hydrogen phosphate on setting reaction and mechanical strength of hydroxyapatite putty.

The setting reaction and mechanical strength in terms of diametral tensile strength (DTS) of hydroxyapatite (HAP) putty made of tetracalcium phosphate, dicalcium phosphate anhydrous, and neutral sodium hydrogen phosphate (Na1.8H1.2PO4) solution containing 8 wt % sodium alginate were evaluated as a function of the Na1.8H1.2PO4 concentration. In one condition, HAP putty was placed in an incubator kept at 37 degrees C and 100% relative humidity. In the other condition, immediately after mixing HAP putty was immersed in serum kept at 37 degrees C. Longer setting times and lower DTS values were observed when HAP putty was immersed in serum regardless of the Na1.8H1.2PO4 concentration. The setting times of the HAP putty in both conditions became shorter with an increase in the Na1. 8H1.2PO4 concentration, reaching approximately 7-13 min when the Na1. 8H1.2PO4 concentration was 0.6 mol/L or higher. The DTS value of HAP putty was relatively constant (10 MPa) regardless of the Na1.8H1. 2PO4 concentration (0.2-1.0 mol/L) when HAP putty was kept in an incubator. In contrast, when HAP putty was immersed in serum, the DTS value was dependent on the Na1.8H1.2PO4 concentration. It increased with the Na1.8H1.2PO4 concentration and reached approximately 5 MPa when the Na1.8H1.2PO4 concentration was 0.6 mol/L, after which it showed a relatively constant DTS value. We therefore would recommend a HAP putty that uses 0.6 mol/L Na1.8H1. 2PO4 since at that concentration the putty's setting time (approximately 10 min) is proper for clinical use and it shows good DTS value (approximately 5 MPa) even when it is immersed in serum immediately after mixing.     

Influence of surfactant molecules as air-entraining agent for bone cement macroporosity

Calcium phosphate bone cements (CPBCs) represent a potential synthetic alternative to bone-graft materials in bone surgery applications. CPBCs are biocompatible, bioresorbable, and slowly are replaced by new bone in vivo. However, CPBCs do not develop a macroporosity during setting that would allow fast bone ingrowth and good osteointegration of the implant. For this reason, recent research has approached the problem of inducing macroporosity inside the bone cement without influencing its normal setting. In this study, a new method for obtaining injectable macroporous CPBCs is proposed. It is based on the use of sodium dodecyl sulphate (SDS) as an air-entraining agent. The results have shown that the liquid-to-powder ratio and the SDS concentration, as well as the diameter and the interconnectivity of the macropores, can control the micro- and macroporosity. This new technology can be used to develop and optimize new commercial products for osteoporotic bone filling applications. Furthermore, the presented method also can be used at low temperatures before an operation to produce preformed implants to fit the particular needs of a patient.     

Factors affecting the structure and properties of an injectable self-setting calcium phosphate foam

One of the main challenges in the investigation on calcium phosphate cements (CPC) lies in the introduction of macroporosity, without loosing the self-setting ability and injectability, characteristic of the cement-type materials. The benefits of macroporosity are related to the enhancement of bone regeneration mechanisms, such as angiogenesis and tissue ingrowth. In this work, the feasibility to obtain self-setting injectable macroporous hydroxyapatite foams by the incorporation of a protein-based foaming agent to a CPC is demonstrated. Albumen is combined with an alpha-tricalcium phosphate [Ca3(PO4)2, alpha-TCP] paste, which hydrolyzes to a calcium deficient hydroxyapatite during the setting reaction. A systematic study is presented, where the effect of different processing parameters is analyzed in terms of porosity, setting properties, injectability, and compressive strength. Self-setting foams with porosities up to 70%, which maintain their porous structure after injection, are obtained. These injectable foams can be used both for direct in vivo applications and for the fabrication of low temperature tissue engineering scaffolds.     

Development of a strontium-containing hydroxyapatite bone cement

A new route was developed to synthesis a new type of strontium-containing hydroxyapatite (Sr-HAP) bone cement with precursors of tetracalcium phosphate (TTCP), strontium hydrogen phosphate (DSPA), dicalcium phosphate (DCPA), phosphate acid and water. The processing parameters and fundamental properties including pH value, setting time, compressive strength of final hardened body and the cytotoxicity for serial extracts of each cements were investigated. The result shows that the final product of the cement after setting for 24h is nonstoichiometic Sr-containing hydroxyapatite (Ca(10-m-x)Sr(x) square(m)(HPO4)y(PO4)6-y(OH)2-2m square2m, 0相似文献   

Self-setting bioactive calcium-magnesium phosphate cement with high strength and degradability for bone regeneration

Calcium phosphate cement (CPC) has been successfully used in clinics as bone repair biomaterial for many years. However, poor mechanical properties and a low biodegradation rate limit any further applications. Magnesium phosphate cement (MPC) is characterized by fast setting, high initial strength and relatively rapid degradation in vivo. In this study, MPC was combined with CPC to develop novel calcium-magnesium phosphate cement (CMPC). The setting time, compressive strength, phase composition of hardened cement, degradation in vitro, cells responses in vitro by MG-63 cell culture and tissue responses in vivo by implantation of CMPC in bone defect of rabbits were investigated. The results show that CMPC has a shorter setting time and markedly better mechanical properties than either CPC or MPC. Moreover, CMPC showed significantly improved degradability compared to CPC in simulated body fluid. Cell culture results indicate that CMPC is biocompatible and could support cell attachment and proliferation. To investigate the in vivo biocompatibility and osteogenesis, the CMPC samples were implanted into bone defects in rabbits. Histological evaluation showed that the introduction of MPC into CPC enhanced the efficiency of new bone formation. CMPC also exhibited good biocompatibility, biodegradability and osteoconductivity with host bone in vivo. The results obtained suggest that CMPC, having met the basic requirements of bone tissue engineering, might have a significant clinical advantage over CPC, and may have the potential to be applied in orthopedic, reconstructive and maxillofacial surgery.     

Comparative study on the properties of acrylic bone cements prepared with either aliphatic or aromatic functionalized methacrylates

Bone cements prepared with methacrylic acid (MAA) and diethyl amino ethyl methacrylate (DEAEM) were compared with formulations employing 4-methacryloyloxybenzoic acid (MBA) and 4-diethyaminobenzyl methacrylate (DEABM) as comonomer. The influence of these new aromatic monomers on various physicochemical, setting and mechanical properties was assessed. Surface characterization demonstrated that bone cements prepared with any of the functionalized monomers exhibited increasing hydrophilicity with monomer concentration and that the aromatic monomers provided more hydrophilic cements than their aliphatic counterparts for low concentrations of the functional monomer. It was also found that bone cements prepared with high amounts of the acidic aliphatic monomer provided the highest exotherm of reaction and their setting times were shorter than MBA based cements. On the other hand, DEABM containing bone cements exhibited shorter setting times than DEAEM formulations and slightly higher peak temperatures. In general, it was found that the glass transition temperature increased with the presence of acidic comonomer and decreased when alkaline comonomers were present, especially aliphatic ones. When aromatic methacrylates were used at 0.05 molar fraction, the highest tensile and compressive strength were achieved i.e. 46 and 118 MPa for MBA and 51 and 108 MPa for DEABM formulations. A further increase in the aromatic monomer concentration led to cements of low mechanical properties due to solubility problems as revealed by SEM.     

Effect of cold-setting calcium- and magnesium phosphate matrices on protein expression in osteoblastic cells

Bone loss due to accidents or tissue diseases requires replacement of the structure by either autografts, allografts, or artificial materials. Reactive cements, which are based on calcium phosphate chemistry, are commonly used in nonload bearing areas such as the craniofacial region. Some of these materials are resorbed by the host under physiological conditions and replaced by bone. The aim of this study was to test different calcium and magnesium cement composites in vitro for their use as bone substitution material. Phase composition of calcium deficient hydroxyapatite (Ca(9) (PO(4) )(5) HPO(4) OH), brushite (CaHPO(4) ·2H(2) O), and struvite (MgNH(4) PO(4) ·6H(2) O) specimens has been determined by means of X-ray diffraction, and compressive strength was measured. Cell growth and activity of osteoblastic cells (MG 63) on the different surfaces was determined, and the expression of bone marker proteins was analyzed by western blotting. Cell activity normalized to cell number revealed higher activity of the osteoblasts on brushite and struvite when compared to hydroxyapatite and also the expression of osteoblastic marker proteins was highest on brushite scaffolds. While brushite sets under acidic conditions, formation of struvite occurs under physiological pH, similar to hydroxyapatite cements, providing the possibility of additional modifications with proteins or other active components.     

Energy dispersive X-ray diffraction study of phase development during hardening of calcium phosphate bone cements with addition of chitosan

The aim of this work was to study the phase transformation during the setting reaction of two calcium phosphate bone cements based on either alpha tricalcium phosphate (alpha-TCP) or tetracalcium phosphate (TetCP) initial solid phase, and a magnesium carbonate-phosphoric acid solution as the hardening liquid. Low molecular weight (38.2 kDa) chitosan was used to retard the cement's setting reaction. To follow the kinetics of the phase development, an energy dispersive X-ray diffraction technique was applied. This technique allowed the collection of diffraction patterns from the cement pastes in situ starting from 1 min of the setting process. In the case of the TetCP-based cement, the appearance and evolution of an intermediate phase was detected.     

Advantages of using glycolic acid as a retardant in a brushite forming cement

In this study we have compared the effect of using acetic, glycolic, and citric acids on the brushite cement setting reaction and the properties of the resultant cement. The cement solid phase was made by mixing beta-tricalcium phosphate (beta-TCP), monocalcium dihydrogen phosphate anhydrate (MCPA), and sodium pyrophosphate, whereas the cement liquid phase consisted of aqueous solutions of carboxy acids at concentrations ranging from 0.5 to 3.5M. Cements were prepared by mixing the solid phase with the liquid phase to form a workable paste. The cement setting time was longer for glycolic and citric acids. The best mechanical properties in dry environments were obtained using glycolic and citric acid liquid phases. In a wet environment at 37 degrees C, the cement set with glycolic acid was the strongest one. Brushite cement diametral tensile strength seems to be affected by the calcium-carboxyl phase produced in the setting reaction. The acceptable setting time and mechanical properties of cements set in glycolic acid solutions are attributed to the additional hydrophilic groups in the carboxylic acid and the low solubility in water of the calcium salt produced in the reaction. Moreover, at high concentrations, carboxylic acids add chemically to the cement matrix becoming reactants themselves.