Basic properties of apatite cement containing spherical tetracalcium phosphate made with plasma melting method

Apatite cement (AC) can be injected through syringe and forms apatite mass. Therefore, AC is very useful for a minimally invasive surgical operation aimed for the reconstruction of bone defects. However, injectability of current AC is not satisfactory for its clinical use. In this investigation, therefore, spherical tetracalcium phosphate (s-TTCP) was prepared with plasma melting method and its effect on injectability were evaluated as well as other basic properties of AC. We found much better handling property and injectability when we used s-TTCP as a component of AC (s-AC). For example, cement spread area used as an index of consistency of the s-AC paste was 512 mm2 whereas that of ordinary AC with irregular TTCP (i-AC) was 158 mm2 when powder to liquid mixing ratio was 2.5. However, diametral tensile strength of set s-AC (1.4 MPa) was significantly lower than that of set i-AC (10.7 MPa) when the powder to liquid ratio was 4.0. X-ray powder diffraction analysis revealed limited formation of apatite in the case of s-AC. Although there are some drawbacks, we feel the use of spherical particle is very useful to improve the injectability of AC. Therefore, it is important to find suitable method to prepare spherical powder as the component of AC.     

Self-hardening calcium deficient hydroxyapatite/gelatine foams for bone regeneration

In this work gelatine was used as multifunctional additive to obtain injectable self-setting hydroxyapatite/gelatine composite foams for bone regeneration. The foaming and colloidal stabilization properties of gelatine are well known in food and pharmaceutical applications. Solid foams were obtained by foaming liquid gelatine solutions at 50°C, followed by mixing them with a cement powder consisting of alpha tricalcium phosphate. Gelatine addition improved the cohesion and injectability of the cement paste. After setting the foamed paste transformed into a calcium deficient hydroxyapatite. The final porosity, pore interconnectivity and pore size were modulated by modifying the gelatine content in the liquid phase.     

Comparison of a low molecular weight and a macromolecular surfactant as foaming agents for injectable self setting hydroxyapatite foams: Polysorbate 80 versus gelatine

Hydroxyapatite foams are potential synthetic bone grafting materials or scaffolds for bone tissue engineering. A novel method to obtain injectable hydroxyapatite foams consists in foaming the liquid phase of a calcium phosphate cement. In this process, the cement powder is incorporated into a liquid foam, which acts as a template for macroporosity. After setting, the cement hardens maintaining the macroporous structure of the foam. In this study a low molecular weight surfactant, Polysorbate 80, and a protein, gelatine, were compared as foaming agents of a calcium phosphate cement. The foamability of Polysorbate 80 was greater than that of gelatine, resulting in higher macroporosity in the set hydroxyapatite foam and higher macropore interconnectivity. Gelatine produced less interconnected foams, especially at high concentrations, due to a higher liquid foam stability. However it increased the injectability and cohesion of the foamed paste, and enhanced osteoblastic-like cell adhesion, all of them important properties for bone grafting materials.     

Development of a fully injectable calcium phosphate cement for orthopedic and dental applications

A study on the development of a fully injectable calcium phosphate cement for orthopedic and dental applications is presented. The paper describes its characteristic properties including results of biocompatibility studies. A conventional two-component calcium phosphate cement formulation (having a powder part containing dry mixture of acidic and basic calcium phosphate particles and a liquid part containing phosphate solution) is modified with a biocompatible gelling agent, to induce flow properties and cohesion. The quantity of the gelling agent is optimized to get a viscous paste, which is smoothly injectable through an 18-gauge needle, with clinically relevant setting parameters. The new formulation has a setting time of 20 min and a compressive strength of 11 MPa. The X-ray diffraction, Fourier transform infrared spectrometry, and energy dispersive electron microprobe analyses showed the phase to be hydroxyapatite, the basic bone mineral. Scanning electron microscopy revealed a porous structure with particle sizes of a few micrometers. The cement did not show any appreciable dimensional or thermal change during setting. The injectability is estimated by extruding through needle and the cohesive property is assessed by water contact method. The cement passed the in vitro biocompatibility screening (cytotoxicity and haemolysis) tests.     

Production of in-situ macropores in an injectable calcium phosphate cement by introduction of cetyltrimethyl ammonium bromide

In the present study, cetyltrimethyl ammonium bromide (CTAB) was introduced to an injectable calcium phosphate cement (CPC) to produce macropores during the setting process to accelerate the absorbing ability in vivo. The effects of CTAB on the rheological properties, injectability, setting time, compressive strength, phase evolution, microstructure and degradation rate of CPC were studied. The results showed that the addition of CTAB increased the viscosity and yield stress, and decreased the injectability of the cement pastes. The macroporosity and total porosity increased and the compressive strength of the cement obviously decreased with the increase of CTAB. The macroporosity of the CPC prepared at 5 mM CTAB solution reached 44.2 +/- 2.5% and the mass loss of the cement increased almost 50% as compared with the cement without CTAB. Considering the injectability, compressive strength and degradation rate of CPC, the preferred CTAB concentration was 5 mM. The injectable CPC with macropores is promising to be used in minimally invasive approach.     

Rheological properties of an apatitic bone cement during initial setting

One scientific and technological aspect of main importance to the medical profession is to develop injectable calcium phosphate cements (CPCs) to be used through minimally invasive surgery techniques with still suitable mechanical and biodegradable properties. The objective of this research was to study the influence of several technological factors on the injectability of CPCs. This was performed by studying the rheological behavior of the cement pastes during their initial setting. Cement rheology was approached by looking at the creep response of apatitic cements as a function of the shear stress, the liquid-to-solid (L/S) ratio, the temperature and the addition of organic admixtures. Results showed creep experiments to be a finer method to detect characteristic setting times than other established subjective procedures. However, of all transition times detected none but the dough time seems to be of relevant importance when injectability of cement is concerned. Creep experiments also showed that the addition of organic admixtures such as citric acid increased injectability by retarding the hydration time.     

Mechanical and rheological properties and injectability of calcium phosphate cement containing poly (lactic-co-glycolic acid) microspheres

To enhance tissue ingrowth and promote rapid resorption, efforts were made to build macropores into calcium phosphate cement (CPC); however, this led to a decrease in its mechanical properties. In this study, poly (lactic-co-glycolic acid) (PLGA) microspheres were incorporated into CPC to impart macroporosity and maintain early strength. The influences of the content of PLGA microspheres on the mechanical strength, rheological properties, injectability, setting time, and microstructure of CPC were also systematically investigated. At the PLGA to CPC mass ratios of 20/80 and 30/70, the compressive strength of the composites was similar to that of CPC without PLGA microspheres. The rheological results indicated that PLGA microspheres/CPC pastes showed plastic and shear-thinning behaviors. The addition of PLGA microspheres to CPC resulted in the increase of viscosity and yield stress of the pastes. Simultaneously, the injectability of the pastes decreased with the addition of PLGA microspheres. When the PLGA to CPC ratio was 20/80, the injectability of the paste was still higher than 95%. The calcium phosphate cement containing 20 wt.% PLGA microspheres exhibited excellent injectability and satisfactory setting time without strength degradation. Obviously, such an in situ macropores-generable CPC should have potential prospects for the wider applications in orthopedics, oral, and maxillofacial surgery.     

Injectability and mechanical properties of magnesium phosphate cements

Up to now magnesium phosphate cements are mainly being utilized in wastewater treatment due to their adsorptive properties. Recently they also have been shown to have a high potential as degradable biocements for application as replacement materials for bone defects. In comparison to degradable calcium phosphate cements they have the advantage of setting at neutral pH, which is favorable in biological environment. In this study two parameters of the cement composition, namely powder-to-liquid ratio (PLR) and citrate content, were varied in order to optimize the injectability properties of the cement paste and the mechanical properties of the reaction product. These properties were determined by means of testing setting time and temperature, paste viscosity, and injectability as well as phase composition and compressive strength of the set cements. Best results were obtained, when the cements were prepared with a PLR of 2.5 and a binder liquid consisting of an aqueous solution of 3 mol/l diammonium hydrogen phosphate and 0.5 mol/l diammonium citrate.     

可注射镁基磷酸钙骨水泥的研究

采用MgO、KH₂PO₄、β-TCP、葡萄糖作为骨水泥的固相, 磷酸溶液作为液相, 制备可注射镁基磷酸钙骨水泥(IMPC)。考察液固比(LPR)、MgO含量、葡萄糖含量变化对IMPC胶凝性能和力学性能的影响。实验结果显示: 液固比和缓凝剂葡萄糖含量增大均会导致凝结时间变长和抗压强度下降, 但有益于可注射性; 随MgO含量增大, 凝结时间缩短, 可注射率降低, 但抗压强度提高。采用正交实验法确定MgO含量26wt%, 液固比0.30 mL/g, 葡萄糖含量6wt%时得到的IMPC综合性能良好, 水化过程缓和, 放热量低。该IMPC有望成为一种新型骨粘结材料。     

磷酸钙骨粘合剂的研究

在柠檬酸中添加壳聚糖配成的固化液与磷酸钙骨水泥(CPC)调和制备的骨修复材料具有类似口香糖的胶状特性, 可应用于碎骨粘结, 称之为磷酸钙骨粘合剂(CPCBA)。本研究考察了柠檬酸的含量对抗压强度、固化时间、水化产物和粘结强度的影响, 同时对该体系进行了初步的体外生物学评价。结果显示, 加入柠檬酸可以缩短固化时间并且时间可以通过柠檬酸的含量进行调控, 同时也改善了抗水性能。壳聚糖可以与骨水泥中的钙离子发生螯合作用, 可以增加界面的粘结强度。小鼠原成骨细胞(MC3T3-E1)在其表面粘附良好, 该体系骨水泥有望取代PMMA成为新的骨粘结剂。     

Calcium–phosphate–silicate composite bone cement: self-setting properties and in vitro bioactivity

In this study, a novel low temperature setting calcium phosphate–silicate cement was obtained by mixing CaHPO₄ · 2H₂O (DCPD) and Ca₃SiO₅ (C₃S) with 0.75 M sodium phosphate buffers (pH = 7.0) as liquid phase. The self-setting properties of the obtained DCPD/C₃S paste with liquid to powder ratio (L/P) of 0.6 ml/g, such as setting times, injectability, degradability and compressive strength were investigated and compared with that of DCPD/CaO cement system. The results indicated that, with the weight ratio of C₃S varied from 20% to 40%, the workable DCPD/C₃S pastes could set within 20 min, and the hydrated cement showed significantly higher compressive strength (around 34.0 MPa after 24 h) than that of the DCPD/CaO cement system (approximately 10.0 MPa). Furthermore, the in vitro pH value of the cements was investigated by soaking in simulated body fluid (SBF) for 12 h, and the result indicated that the DCPD/C₃S did not induce significant increase or decrease of pH value in SBF. Additionally, the composite cement possesses better ability to support and stimulate cell proliferation than the DCPD/CaO cement. With good hydraulic properties, improved biocompatibility and moderate degradability, the novel DCPD/C₃S bone cement may be a potential candidate as bone substitute.     

氧化锌对纳米羟基磷灰石/壳聚糖复合骨水泥理化性能的影响

质量比为70∶30的n-HA/CS复合材料与适量ZnO粉末的共混物为固相,选用合适的固化液,按照适当的固/液比例进行调和,制备出一种在空气、生理盐水及血液或体液中均可快速固化的新型n-HA/CS复合骨水泥,考查了ZnO含量对该骨水泥理化性能的影响.结果表明:当ZnO与复合材料质量比为1∶8、固化液与固相粉末比例(L/P)为1.2ml/g时,所制备的复合骨水泥抗压强度和固化时间均较佳,能够满足临床操作的需要.ZnO/复合材料质量比分别为1∶8和1∶5的骨水泥在生理盐水中的pH值随浸泡时间的延长而逐渐升高,前者在第20d时pH值维持在7.28左右,而后者在第20d时的pH值接近7.40,均与人体的pH环境相近.当ZnO/复合材料质量比为1∶8时,骨水泥对水的接触角最小,表明其具有良好的润湿性能.ZnO含量越高,骨水泥的吸水率越低,这对于保持骨水泥植入体内后的体积稳定性具有重要价值.SEM观察发现,固化后的骨水泥中含有大量微孔,有利于营养物质的传递及代谢废物的排泄,并利于新生骨组织的长入及爬行替代.     

Calcium phosphate bone cements for clinical applications. Part II: Precipitate formation during setting reactions

Calcium phosphate bone cements (CPBC) have been of great interest in medicine and dentistry due to their excellent biocompatibility and bone-repair properties. In this article, a review is presented of the scientific literature concerning precipitate formation during setting reactions of CPBCs. Firstly, the available information has been classified according to the intended final product or calcium phosphate formed during setting reactions. Taking the final product into account, a second classification has been made according to the calcium phosphates present in the original powder mixture. This is the most natural classification procedure because it is based on thermodynamic reasons supported by solubility diagrams for the calcium phosphate salts. By understanding the thermodynamics of calcium phosphate salts in an aqueous solution at room or body temperature it is possible to optimize the manufacturing technology involved in the production of CPBCs. Knowledge of the limitations of this thermodynamic approach opens up new possibilities in the search for CPBCs with better in vitro and in vivo properties for clinical applications. © 1999 Kluwer Academic Publishers     

Effects of glass ionomer cements on bone tissue

In vivo biocompatibility of glass ionomer cements (GICs) was evaluated for use in orthopaedic surgery using a rat model and compared with conventional bone cement, Polymethyl methacrylate, PMMA. The unset GICs and PMMA were inserted into the marrow cavities of rat femora and retained in situ for various periods of time. The PMMA bone cement showed complete biocompatibility with no interference with reparative bone. The conventional GIC with smaller glass particles and lower powder/liquid ratio showed an initial minor toxic effect on rat bone tissue with later disturbance of adjacent bone formation. The conventional GIC with larger-size glass particles and higher powder/liquid ratio and resin-modified GIC showed more severe toxic effect on rat tissue with the resin-modified GIC affecting the rat bone tissue later. The causes of toxicity associated with the conventional GIC with larger glass particles and higher powder/liquid ration and the resin-modified GIC are thought to be related with the unreacted acid component of both materials and longer ongoing metallic ion release.     

Injectable magnesium-doped brushite cement for controlled drug release application

Dicalcium phosphate dihydrate (CaHPO₄·2H₂O), also known as brushite, is one of the important bioceramics for bone regeneration. However, fast setting of the brushite cement under physiological conditions has limited its clinical use. Furthermore, brushite cement without any additives normally has poor injectability due to the liquid–solid phase separation. In the present study, magnesium-doped β-tricalcium phosphate (Mg-β-TCP) with chemical formula of β-Ca_2.96?x Mg _x (PO₄)₂ was used to prepare injectable brushite cements with improved physicochemical properties. β-TCP containing different amounts of Mg²⁺ ions were reacted with monocalcium phosphate monohydrate [Ca(H₂PO₄)₂·H₂O, MCPM] in the presence of water to furnish corresponding brushite cement. The samples were characterized using X-ray diffractometry, Fourier transform infrared spectroscopy and field emission scanning electron microscopy. The effect of magnesium ions on the structural, mechanical, and setting properties of the cements is reported. Our results indicate that the presence of Mg²⁺ ions increases the degree of injectability, setting time, and mechanical properties of the brushite cement. The compressive strength of brushite cement was substantially increased upon incorporation of Mg²⁺ ions. Furthermore, the setting times of the brushite cement were significantly improved. Gentamicin sulfate, amoxicillin and ampicillin trihydrate were incorporated into the Mg-brushite cement, and their release profiles showed a sustained drug release over 14 days. Cumulative releases of 99.3, 87, and 79 % were observed for gentamicin sulfate, amoxicillin, and ampicillin trihydrate, respectively.     

Injectability evaluation of tricalcium phosphate bone cement

Calcium phosphate cements are biomaterials made from a mixture of calcium phosphate powder in aqueous solutions that forms a paste that reacts at the body temperature and hardens as a result of precipitation reactions. These cements are commonly used in dentistry and orthopedic bone filling surgeries, which require extremely invasive procedures. The challenge consists in formulating an injectable paste by additives incorporation. In this work, three different additives (carboxymethylcellulose, agar polymer and sodium alginate) were incorporated to tricalcium phosphate, in concentrations of 0.4, 0.8, 1.6, 3.2 and 6.4 wt.%. Injectability was evaluated through a new method developed for this purpose. Results showed that it was possible to obtain injectable compositions of α-tricalcium phosphate cement. It was verified that the injectability depends on the rheological behavior of the pastes and injection time. In this study, pastes with viscosity suitable for good homogenization and injection were obtained.     

Study of a hydraulic DCPA/CaO-based cement for dental applications

A CPC was obtained by mixing calcium hydrogenphosphate (DCPA: CaHPO₄) and calcium oxide with either water or sodium phosphate (NaP) buffers. Physical and mechanical properties such as compressive strength (CS), initial (I) and final (F) setting times, cohesion time (T_C), dough time (T_D), swelling time (T_S), dimensional and thermal behavior, injectability (t_100%), antimicrobial properties, setting reaction kinetics, and powder stability over time were investigated by varying different parameters such as liquid-to-powder (L/P) ratio (0.35 to 0.7 mL g⁻¹), molar calcium-to-phosphate (Ca/P) ratio (1.67 to 3), the pH (4, 7 or 9) and the concentration (0 to 1 M) of the NaP buffer. The best results were obtained with the pH 7 NaP buffer at a concentration of 0.75 M. With this liquid phase, physical and mechanical properties depended on the Ca/P and L/P ratios, varying from 3 to 11 MPa (CS), 6 to 10 min (I), 11 to 15 min (F), 15 to 45 min (T_S), 3 to 12 min (t_100%), 16 min (T_D). This cement expanded during its setting (2.5–7%), and is thus appropriate for tight filling. Finally the cement has antimicrobial activity from Ca/P = 2 and the whole properties were conserved after 8 months storage. Given the mechanical, rheological and antimicrobial properties of this new DCPA/CaO-based cement, its use as root canal sealing or pulp capping material may be considered as similar to calcium hydroxide or ZnO/eugenol-based pastes, without or with a gutta-percha point.     

Evaluation of colloidal silica suspension as efficient additive for improving physicochemical and in vitro biological properties of calcium sulfate-based nanocomposite bone cement

In the present study new calcium sulfate-based nanocomposite bone cement with improved physicochemical and biological properties was developed. The powder component of the cement consists of 60 wt% α-calcium sulfate hemihydrate and 40 wt% biomimetically synthesized apatite, while the liquid component consists of an aqueous colloidal silica suspension (20 wt%). In this study, the above mentioned powder phase was mixed with distilled water to prepare a calcium sulfate/nanoapatite composite without any additive. Structural properties, setting time, compressive strength, in vitro bioactivity and cellular properties of the cements were investigated by appropriate techniques. From X-ray diffractometer analysis, except gypsum and apatite, no further phases were found in both silica-containing and silica-free cements. The results showed that both setting time and compressive strength of the calcium sulfate/nanoapatite cement improved by using colloidal silica suspension as cement liquid. Meanwhile, the condensed phase produced from the polymerization process of colloidal silica filled the micropores of the microstructure and covered rodlike gypsum crystals and thus controlled cement disintegration in simulated body fluid. Additionally, formation of apatite layer was favored on the surfaces of the new cement while no apatite precipitation was observed for the cement prepared by distilled water. In this study, it was also revealed that the number of viable osteosarcoma cells cultured with extracts of both cements were comparable, while silica-containing cement increased alkaline phosphatase activity of the cells. These results suggest that the developed cement may be a suitable bone filling material after well passing of the corresponding in vivo tests.     

Injectable collagen/α-tricalcium phosphate cement: collagen–mineral phase interactions and cell response

A bone inspired material was obtained by incorporating collagen in the liquid phase of an α-tricalcium phosphate cement, either in solubilized or in fibrilized form. This material was able to set in situ, giving rise to a calcium deficient hydroxyapatite (CDHA)/collagen composite. The morphology and distribution of collagen in the composite was shown to be strongly affected by the collagen pre-treatment. The interactions between collagen and the inorganic phase were assessed by FTIR. A red shift of the amide I band was indicative of calcium chelation by the collagen carbonyl groups. The rate of CDHA formation was not affected when diluted collagen solutions (1 mg/ml) were used, whereas injectability improved. The presence of solubilized collagen, even in low amount (1 %), increased cell adhesion and proliferation on the composites. Still in the absence of osteogenic medium, significant ALP activity was detected both in the inorganic and the collagen-containing cements. The maximum ALP activity was advanced in the collagen-containing cement as compared to the inorganic cement.     

Preparation and evaluation of an experimental luting glass ionomer cement to be used in dentistry

The aim of this paper is to compare the fluoride-releasing and mechanical properties of an experimental luting glass ionomer cement, which has a modified composition and a commercial luting cement. The experimental powder was obtained by sol–gel process and then, it was used to prepare the experimental cements. The properties of cement pastes, such as setting time and working time, microhardness and diametral tensile strength were determined. Fluoride release from GICs was evaluated at time intervals of 1, 7, 14, 21 and 28 days in deionized water. Atomic force microscopy (AFM) analyses showed that the surface of the experimental cements is more homogeneous than commercial GICs. The mechanical properties and the measure of liberation of fluoride of the two cements were influenced by ratio powder:liquid and chemical composition of the precursor powders. Experimental cements released less fluoride than commercial cements. However, this liberation was more constant during the analyzed period. Thus, the results obtained in this study indicated that the composition of the experimental powder modified by the niobium can lead the formation of the polysalt matrix with good mechanical properties. In other words, we can say that experimental powder offered considerable promise for exploitation in dental field.