Brushite Bone Cement Research Articles

Effect of Apatite Wollastonite Glass Ceramic Addition on Brushite Bone Cement Containing Chitosan

Apatite wollastonite glass ceramic (AW-GC) (34.2% SiO2, 44.9% CaO, 16.3%P2O5, 4.6% MgO, 0.5% CaF2) was added into a brushite bone cement, which composed of β-tricalcium phosphate (β-Ca3(PO4)2, β-TCP) and monocalcium phosphate monohydrate (Ca (H2PO4)2H2O, MCPM) in powder phases. Cement was prepared using a 3 β-TCP:2 MCPM in weight ratio. To evaluate the effect of AW-GC on the mechanical strength and degradability of brushite bone cement, the powder phases and 1 wt.% of chitosan dissolved in 5 wt.% of citric acid solution were mixed and soaked in simulated body fluid solution at 37 °C for 1, 3, 5,7 and 14 days, respectively. The compressive strength and setting time of AW-GC added in brushite bone cement were studied and compared with pure brushite cement. The pH values increased with addition of AW-GC. Additionally, the obtained brushite bone cements were characterized by XRD, SEM techniques.

Nisin F-loaded brushite bone cement prevented the growth of Staphylococcus aureus in vivo

To determine if nisin F-loaded self-setting brushite cement could control the growth of Staphylococcus aureus in vivo. Brushite cement was prepared by mixing equimolar concentrations of β-tricalcium phosphate and monocalcium phosphate monohydrate. Nisin F was added at 5·0, 2·5 and 1·0% (w/w) and the cement moulded into cylinders. In vitro antibacterial activity was determined using a delayed agar diffusion assay. Release of nisin F from the cement was determined using BCA protein assays. Based on scanning electron microscopy and X-ray diffraction analysis, nisin F did not cause significant changes in cement structure or chemistry. Cement containing 5·0% (w/w) nisin F yielded the most promising in vitro results. Nisin F-loaded cement was implanted into a subcutaneous pocket on the back of mice and then infected with S. aureus Xen 36. Infection was monitored for 7 days, using an in vivo imaging system. Nisin F prevented S. aureus infection for 7 days and no viable cells were isolated from the implants. Nisin F-loaded brushite cement successfully prevented in vivo growth of S. aureus. Nisin F incorporated into bone cement may be used to control S. aureus infection in vivo.

Release of Enterococcus mundtii Bacteriocin ST4SA from Self-Setting Brushite Bone Cement.

Maxillofacial and craniofacial surgery is on the increase, which exposes more patients at risk of acquiring microbial infections. The use of antibiotic-loaded calcium phosphate bone cements has been shown to reduce the incidence of infection. A marked increase in antibiotic-resistant pathogens, including multidrug-resistant pathogens, has been reported. This has led to the investigation of various compounds as alternatives to conventional treatments. In this paper, we report on the incorporation and release of a broad-spectrum class II antimicrobial peptide, bacteriocin ST4SA produced by Enterococcus mundtii, into a calcium orthophosphate-based bone cement. Our results suggest class II bacteriocins may be incorporated into self-setting bone cements to produce implants with antimicrobial activity over extended periods of time.

Factors affecting the longevity and strength in an in vitro model of the bone-ligament interface.

The interfaces between musculoskeletal tissues with contrasting moduli are morphologically and biochemically adapted to allow the transmission of force with minimal injury. Current methods of tissue engineering ligaments and tendons do not include the interface and this may limit the future clinical success of engineered musculoskeletal tissues. This study aimed to use solid brushite cement anchors to engineer intact ligaments from bone-to-bone, creating a functional musculoskeletal interface in vitro. We show here that modifying anchor shape and cement composition can alter both the longevity and the strength of an in vitro model of the bone–ligament interface: with values reaching 23 days and 21.6 kPa, respectively. These results validate the use of brushite bone cement to engineer the bone–ligament interface in vitro and raise the potential for future use in ligament replacement surgery.

Preparation and properties of macroporous brushite bone cements

In the present work a macroporous brushite bone cement for use either as an injected or mouldable paste, or in the shape of preformed grafts, has been investigated. Macropores have been introduced by adding to the powder single crystals of mannitol which worked as a porogen. The size of the crystals was in the range of 250–500 μm in diameter, suitable for cell infiltration, with a shape ratio between 3 and 6. From compression tests on cylindrical samples an elastic modulus in the range 2.5–4.2 GPa and a compressive strength in the range 17.5–32.6 MPa were obtained for a volume fraction of macropores varying between 15 and 0%. Thus the compressive strength exceeded in all tests the maximum value currently attributed to cancellous bone.

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

Bioactive composite bone cements were obtained by incorporation of tricalcium silicate (Ca 3SiO 5, C 3S) into a brushite bone cement composed of β-tricalcium phosphate [β-Ca 3(PO 4) 2, β-TCP] and monocalcium phosphate monohydrate [Ca(H 2PO 4) 2·H 2O, 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/C 3S composite paste increased with increasing aging time. Moreover, the TCP/MCPM/C 3S 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/C 3S 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/C 3S cements may be used as a bioactive material for bone regeneration, and might have significant clinical advantage over the traditional β-TCP/MCPM brushite cement.

High-strength resorbable brushite bone cement with controlled drug-releasing capabilities

Brushite cements differ from apatite-forming compositions by consuming a lot of water in their setting reaction whereas apatite-forming cements consume little or no water at all. Only such cement systems that consume water during setting can theoretically produce near-zero porosity ceramics. This study aimed to produce such a brushite ceramic and investigated whether near elimination of porosity would prevent a burst release profile of incorporated antibiotics that is common to prior calcium phosphate cement delivery matrices. Through adjustment of the powder technological properties of the powder reactants, that is particle size and particle size distribution, and by adjusting citric acid concentration of the liquid phase to 800 mM, a relative porosity of as low as 11% of the brushite cement matrix could be achieved (a 60% reduction compared to previous studies), resulting in a wet unprecompacted compressive strength of 52 MPa (representing a more than 100% increase to previously reported results) with a workable setting time of 4.5 min of the cement paste. Up to 2 wt.% of vancomycin and ciprofloxacin could be incorporated into the cement system without loss of wet compressive strength. It was found that drug release rates could be controlled by the adjustable relative porosity of the cement system and burst release could be minimized and an almost linear release achieved, but the solubility of the antibiotic (vancomycin > ciprofloxacin) appeared also to be a crucial factor.

Characterization of chlorhexidine-releasing, fast-setting, brushite bone cements

The effect of antibacterial chlorhexidine diacetate powder (CHX) on the setting kinetics of a brushite-forming β-tricalcium phosphate/monocalcium phosphate monohydrate (β-TCP/MCPM) cement was monitored using attenuated total reflection Fourier transform infrared spectroscopy. The final composition of the set cement with up to 12 wt.% CHX content before and after submersion in water for 24 h, the kinetics of chlorhexidine release and the total sample mass change in water over four weeks was monitored using Raman mapping, UV spectroscopy and gravimetry, respectively. Below 9 wt.%, CHX content had no significant effect on brushite formation rate at 37 °C, but at 12 wt.% the half-life of the reaction decreased by one-third. Raman mapping confirmed that brushite was the main inorganic component of the set cements irrespective of CHX content, both before and after submersion in water. The CHX could be detected largely as discrete solid particles but could also be observed partially dispersed throughout the pores of the set cement. The percentage of CHX release was found to follow Fick’s law of diffusion, being independent of its initial concentration, proportional to the square root of time and, with 1 mm thick specimens, 60% was released at 24 h. Total set cement mass loss rate was not significantly affected by CHX content. On average, cements exhibited a loss of 7 wt.% assigned largely to surface phosphate particle loss within the initial 8 h followed by 0.36 wt.% per day.

Effect of Mechanical Mixing and Powder to Liquid Ratio on the Strength and Reliability of a Brushite Bone Cement

The effect of mechanical mixing on compressive strength, relative porosity and reliability of strength data of a brushite forming cement at different powder to liquid ratios (PLRs) was investigated. Mean compressive strengths were measured, associated reliability (Weibull moduli) and survival probability distributions of the data sets were analysed. Relative porosities were determined using helium pycnometry. For low PLR (2.2g/ml), no significant differences in compressive strength were observed for either mechanical or hand mixed samples, although reliability of the former was significantly increased. At high PLR (3.4g/ml), mechanically mixed cements exhibited approximately twice the mean compressive strength compared with hand mixing, although Weibull moduli remained statistically similar. At medium PLR (2.8g/ml) strength and reliability of cements were similar and independent of mixing regime. For all PLRs, a significant decrease in porosity of mechanical- compared with hand-mixed cements was observed. Mechanical mixing of a brushite cement can provide lower porosity, increased reliability and higher strength.

FTIR-monitoring of a fast setting brushite bone cement: effect of intermediate phases

The setting reaction of an equimolar β-tricalcium phosphate/monocalcium phosphate monohydrate (β-TCP/MCPM) cement was monitored in real time with ATR-FTIR at 23 and 37 °C using powder to liquid ratios (PLRs) of 2.0 and 3.3 g ml−1 and aqueous retardant citric acid concentrations of 800, 1000 and 1500 mM. The final set products, for PLRs of 2.0 to 3.3 g ml−1 and citric acid concentrations of 300 to 1500 mM, were characterised with regard to phase composition, compressive strength, density and relative porosity. FTIR provided evidence for the formation of an intermediate dicalcium phosphate–citrate complex (DCPC). As the concentration of citric acid in solution increased so did the maximum level of citrate intermediate. Decreasing the PLR reduced the rate of citrate removal, but had no effect on its rate of formation or maximum level. FTIR also indicated a time delay before formation of any observable dicalcium phosphate (DCP) in solution. This delay increased as the citric acid solution concentration was raised or the temperature reduced, but was less affected by the PLR. There was then an additional delay between DCP formation in solution and its precipitation. Both Rietveld analysis of XRD patterns and density measurements 24 h after setting confirmed that the final product was primarily dicalcium phosphate dihydrate (DCPD or brushite) when the citric acid concentration was less than 1000 mM, irrespective of temperature or PLR. On the other hand, with 1500 mM citric acid significant levels of dicalcium phosphate anhydrous (DCPA or monetite) also present, this led to increased porosity and a dramatic decline in strength. As the levels of the intermediate phase increased, the final wet compressive strength of the resulting cements also deteriorated. It is therefore proposed that strength reduction may be due to formation of the intermediate at early stages of setting or DCPA formation in the final product, both causing increased material inhomogeneity. This study thereby illustrates that real time ATR-FTIR monitoring of a setting reaction clearly indicates that there is an upper limit to the use of citric acid as a setting retardant for a fast setting brushite-forming cement system, a limit that can also be expected for the use of other setting retardants, and that ATR-FTIR monitoring comprises a useful complement to the traditional before–after investigations.

Stearate Salts as Brushite Bone Cement Setting Retardants

This study sought to examine the efficiency of coating cement powder reactants in order to reduce the solubility rate of reactants and thereby increase setting times of cement systems. In this investigation magnesium and sodium stearate salts were used to coat the highly soluble monocalcium phosphate monohydrate (MCPM) powder component of a hydraulic brushite forming calcium phosphate cement system with b-tricalcium phosphate (b-TCP) as other component. The results showed that stearate coating of the MCPM reactant could lead to a 100% increase in setting and working times without affecting compressive strength of the set cement when applied with the appropriate P/L-ratio.