Effect of the calcium to phosphorus ratio on the setting properties of calcium phosphate bone cements

α-Tricalcium phosphate (α-TCP) has become the main reactant of most experimental and commercial ceramic bone cements. It has calcium-to-phosphorus (Ca/P) ratio of 1.50. The present study expands and reports on the microstructures and mechanical properties of calcium phosphate (CP) cements containing sintered monolithic reactants obtained in the interval 1.29??1.50 were composed of α-TCP, tetracalcium phosphate and hydroxyapatite; (d) only the reactant with Ca/P?=?1.50 was monophasic and was made of α-TCP, which transformed during the setting into calcium deficient hydroxyapatite; (e) CP-cements developed different crystal microstructures with specific features depending on the Ca/P ratio of the starting reactant.     

Preparation and properties of some magnesium-containing calcium phosphate cements

Attempts were made to prepare magnesium-containing calcium phosphate cements. These were successful at the composition CaMg₂(PO₄)₂xH₂O. X-ray diffraction showed that such a compound is not formed but that the cement consists of magnesium phosphate precipitated on the calcium phosphate admixture. The pH of this formulation is around 10 during setting and after. The cement is injectable. Its setting time is about 10 min. In this study compressive strength values were as high as 11 MPa and the diametral tensile strength was over 2 MPa. Animal experiments must show whether it is suitable for replacement or augmentation of bone in non-load bearing situations.     

Short-term dissolution behaviour of some calcium phosphate cements and ceramics

Abstracts are not published in this journal This revised version was published online in November 2006 with corrections to the Cover Date.     

pH-metric study of the setting reaction of monocalcium phosphate monohydrate/calcium oxide-based cements

Hydraulic calcium phosphate cements (CPCs) that are used as osseous substitutes, set by an acid–base reaction between an acid calcium phosphate and a basic calcium salt (often a phosphate). In order to gain a better understanding of the setting of the monocalcium phosphate monohydrate–calcium oxide cement that we developed and in the aim to improve its mechanical properties, the setting reaction was studied by pH-metry. The two methods described in the literature were used. In the first, cement samples were prepared then crushed after different storage periods at 37 °C, 100% RH. The powder was then immersed in pure water with stirring and the pH was measured after equilibration. In the second technique, the starting materials were poured into water while stirring and the pH were followed over time. The two methods gave different results. The first procedure provided information concerning the pH of the surrounding liquid following the partial dissolution of the cement components, rather than any information about pH changes during setting. The second method is more appropriate to follow the pH variations during setting. In this second procedure, the effects of different parameters such as crushing time, stirring rate, liquid-to-powder (L/P) ratio and temperature were investigated. These parameters may impact substantially on the shape and position of the pH=f(t) curves. One or three pH jumps were observed during the setting depending on the composition of the liquid phase. The time at which these pH jumps occurred depended on the pH of the liquid phase, the concentration of the buffer, the crushing of starting materials, the L/P ratio and the temperature. Good linear correlations were obtained (i) between the time of the pH jumps and the L/P ratio and the temperature and (ii) between the time of the first pH jump and the compressive strength and the final setting time of the cements prepared with different liquid phases. It may be assumed in view of these correlations that the results obtained in dilute solution may be extrapolated to the conditions of cement sample preparation and that the mechanical properties of the cement are directly related to the phenomena that occur at the first pH jump which corresponds to precipitation of dicalcium phosphate dihydrate.     

Microsphere-filled lightweight calcium phosphate cements

The incorporation of inorganic and organic microsphere fillers into calcium phosphate cement (CPC) to produce lightweight cementitious materials that could be used under hydrothermal conditions at high temperatures between 200 and 1000 °C was investigated. An aluminosilicate based hollow microsphere, with a density of 0.67 gcm^–3 and a particle size of 75–200 m, was the most suitable having a low slurry density of 1.3 gcm^–3, and a compressive strength greater than 6.89 M Pa. This microsphere-filled lightweight CPC exhibited the following characteristics: 1. after autoclaving at 200 °C, amorphous ammonium calcium orthophosphate (AmCOP) salt and Al₂O₃·xH₂0 gel phases, formed by the reaction between calcium aluminate cement and an NH₄H₂P0₄ based fertilizer, were primarily responsible for the development of strength; 2. at a hydrothermal temperature of 300 °C, the microsphere shell moderately reacted with the CPC to form an intermediate reaction product, epistilbite (EP), while crystalline hydroxyapatite (HOAp) and boehmite (BO) were yielded by the phase transformations of AmCOP and Al₂O₃·xH₂O, respectively; 3. at an annealing temperature of 600 °C, the HOAp phase remained in the cement body, even though an EP anorthite (AN) phase transition occurred; 4. at 1000 °C, the phase conversion of HOAp into whitlockite was completed, while the AN phase was eliminated; and 5. the microsphere demonstrated excellent thermal stability up to temperatures of 1000 °C.This work was performed under the auspices of the US Department of Energy, Washington, DC, under Contract No. DE-AC02-76CH00016.     

Formulation and setting times of some calcium orthophosphate cements: a pilot study

Calcium orthophosphates which either can be formed by precipitation at room or body temperatures or by reactions at higher temperatures have been reviewed. Most formulations of cements contain at least one or more acidic components and one or more basic components which react when the powder is mixed with water. Several combinations of reactants are possible in the systems of calcium phosphates and even combinations with calcium phosphates containing sodium, potassium, magnesium, zinc, carbonate or chloride are thought to be useful. Furthermore, other compounds can be added as accelerators or retarders of the setting reaction or as promoters of bone ingrowth. In this study, over 100 formulations have been tested on their ability to set upon mixing with water. The initial and final setting times were measured with Gilmore needles.     

Effect of various additives and temperature on some properties of an apatitic calcium phosphate cement

The effect of additives and temperature on setting time, swelling time and compressive strength of a previously developed apatitic calcium phosphate cement was investigated. Setting was faster at body temperature than at room temperature. Early contact with aqueous solutions resembling blood and other body fluids had no effect. Deliberate additions of soluble carbonates, pyrophosphate or magnesium salts to the cement powder retarded or even inhibited setting. However, additions of calcium pyrophosphate, -tertiary calcium phosphate or sintered hydroxyapatite to the cement powder in amounts up to 10% had no effect on the cement properties. Several organic substances were used as additives. They all retarded the setting and decreased the strength of the cement considerably.     

Limited compliance of some apatitic calcium phosphate bone cements with clinical requirements

Clinical requirements for calcium phosphate bone cements were formulated in terms of the initial setting time, the final setting time, the cohesion time and the ultimate compressive strength. Two cements were tested. Biocement H was made of a powder containing -tertiary calcium phosphate and precipitated hydroxyapatite. Biocement F was made of a powder containing, in addition, some monetite. The liquid/powder (L/P) ratio was varied over the range 0.30–0.40 ml g-1, whereas the accelerator concentration in the liquid was varied from 0%–4% Na2HPO4 in water. For Biocement H there was no combination L/P ratio and % Na2HPO4 for which all clincal requirements were satisfied. However, Biocement F had a certain area where this was the case. Therefore, it is expected that Biocement F can be applied in clinical situations such as orthopaedics, plastic and reconstructive surgery and oral and maxillofacial surgery, even when early contact with blood is inevitable. © 1998 Kluwer Academic Publishers     

Properties and mechanisms of fast-setting calcium phosphate cements

The setting time of a calcium phosphate cement consisting of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) was reduced from 30 to 5 min by use of a cement liquid that contained a phosphate concentration of 0.25 mol/l or higher. The diametral tensile strength and conversion of the cement ingredients to hydroxyapatite (OHAp) during the first 3 h were also significantly increased by the phosphate. However, the phosphate produced no significant effects on the properties of the 24-h cement samples. Results from additional experiments in a slurry system verified that the high phosphate concentration in the solution accelerated the formation of OHAp in the TTCP + DCPA system, and this reaction could explain the fast-setting properties of the cements.Certain commercial materials and equipment are identified in this paper to specify the experimental procedure. In no instance does such identification imply recommendation or endorsement by the American Dental Association or National Institute of Standards and Technology or that the materials or equipment identified is necessarily the best available for the purpose.     

Application of impedance spectroscopy to evaluate the effect of different setting accelerators on the developed microstructures of calcium phosphate cements

The main goal of the present study was to evaluate the effect of different setting accelerator agents on the developed microstructures of calcium phosphate cements (CPCs) by employing the impedance spectroscopy (IS) technique. Six compositions of CPCs were prepared from mixtures of commercial dicalcium phosphate anhydrous (DCPA) and synthesized tetracalcium phosphate (TTCP) as the solid phases. Two TTCP/DCPA molar ratios (1/1 and 1/2) and three liquid phases (aqueous solutions of Na₂HPO₄, tartaric acid (TA) and oxalic acid (OA), 5% volume fraction) were employed. Initial (I) and final (F) setting times of the cement pastes were determined with Gillmore needles (ASTM standard C266-99). The hardened samples were characterized by X-ray powder diffraction (XRD), Fourier transformed infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and apparent density measurements. The IS technique was employed as a non-destructive tool to obtain information related to porosity, tortuosity and homogeneity of the cement microstructures. The formulation prepared from a TTCP/DCPA equimolar mixture and OA as the liquid phase presented the shortest I and F (12 and 20 min, respectively) in comparison to the other studied systems. XRD analyses revealed the formation of low-crystallinity hydroxyapatite (HA) (as the main phase) as well as the presence of little amounts of unreacted DCPA and TTCP after 24 h hardening in 100% relative humidity. This was related to the proposed mechanisms of dissolution of the reactants. The bands observed by FTIR allowed identifying the presence of calcium tartrate and calcium oxalate in the samples prepared from TA and OA, in addition to the characteristic bands of HA. High degree of entanglement of the formed crystals was observed by SEM in samples containing OA. SEM images were also correlated to the apparent densities of the hardened cements. Changes in porosity, tortuosity and microstructural homogeneity were determined in all samples, from IS results, when the TTCP/DCPA ratio was changed from 1/1 to 1/2. The cement formulated from an equimolar mixture of TTCP/DCPA and OA as the liquid phase presented setting times, degree of conversion to low-crystallinity HA and microstructural features suitable to be used as potential bone cement in clinical applications. The IS technique was shown to be a very sensitive and non-destructive tool to relate the paste composition to the developed microstructures. This approach could be very useful to develop calcium phosphate bone cements for specific clinical demands.     

Some factors controlling the injectability of calcium phosphate bone cements

The injectability of four calcium phosphate bone cements (CPBCs) was measured using a commercial disposable syringe. It varied considerably with the cement powder composition, with the liquid/powder ratio, with the time after starting the mixing of liquid and powder, with the accelerator concentration (% Na2HPO4), and with the ageing time of the cement powder which was prepared by milling. The injectability test could be used to determine accurately the dough time of CPBCs. Relations between the setting time and the cohesion time are discussed.     

Effective formulations for the preparation of calcium phosphate bone cements

In the system CaO–P₂O₅–H₂O 13 different solids with varying Ca/P ratios are known. In addition calcium phosphates containing other biocompatible constituents like Na, or K, or Mg or Cl or carbonate, are known. Therefore, a large number of combinations of such compounds is possible which might result in the formation of calcium phosphate cements upon mixing with water. However, the number of calcium phosphates possibly formed by precipitation at room or body temperatures is limited to 12, which should limit the number of suitable combinations. In this study more than 450 different combinations of reactants have been investigated. The results were evaluated on the basis of the following criteria: (a) was the intended reaction product formed? (b) was the final setting time shorter than 60 min? (c) was the compressive strength after soaking for 1 day in Ringer's solution at 37°C higher than 2 MPa? We found that 15 formulations satisfied all of these criteria. The distribution of cements synthesized in this way was 3 DCPD type, 3 CMP type, 6 OCP type and 3 CDHA type cements. The DCPD type cements were acidic during setting and remained that for a long time afterwards. CDHA type cements were neutral or basic during setting, and remained neutral after completion of the reaction. The OCP type cements were neutral both during and after setting. Two CMP type cements were basic both during and after setting. In this study compressive strengths were found up to 90 MPa. Also, in the literature values up to 90 MPa have been reported for this type of cement. Taking into account the excellent biocompatibility and the good osteoconductivity of calcium phosphates and the fact that these calcium phosphate cements can be injected into the site of operation, it may be expected that these materials will become the materials of choice for bone replacement and augmentation. Their suitability for the fixation of metal endoprostheses for joint replacement should be investigated as well.     

In vivo behaviour of three calcium phosphate cements and a magnesium phosphate cement

Three types of calcium phosphate cements and one magnesium phosphate cement were implanted subcutaneously in rats under exclusion of direct cellular contact. Retrieval times were either 1, 2, 4 or 8 weeks. Before and after retrieval the compressive strength, the diametral tensile strength, the quantitative chemical composition, the qualitative phase composition, the FTIR spectrum and the microstructure were determined. The three calcium phosphate cements maintained their strength during implantation. The phase DCPD was completely transformed into a Na- and CO₃-containing apatite, the phases DCP and CDHA only partially. It could not be ruled out that OCP is also transformed into a bone-mineral-like apatite to a certain extent. That this latter process occurs much faster during the turn-over of living bone, is probably due to the very small crystal size of the OCP particles in bone.     

In vitro studies of calcium phosphate silicate bone cements

A novel calcium phosphate silicate bone cement (CPSC) was synthesized in a process, in which nanocomposite forms in situ between calcium silicate hydrate (C–S–H) gel and hydroxyapatite (HAP). The cement powder consists of tricalcium silicate (C₃S) and calcium phosphate monobasic (CPM). During cement setting, C₃S hydrates to produce C–S–H and calcium hydroxide (CH); CPM reacts with the CH to precipitate HAP in situ within C–S–H. This process, largely removing CH from the set cement, enhances its biocompatibility and bioactivity. The testing results of cell culture confirmed that the biocompatibility of CPSC was improved as compared to pure C₃S. The results of XRD and SEM characterizations showed that CPSC paste induced formation of HAP layer after immersion in simulated body fluid for 7 days, suggesting that CPSC was bioactive in vitro. CPSC cement, which has good biocompatibility and low/no cytotoxicity, could be a promising candidate as biomedical cement.     

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. © 1999 Kluwer Academic Publishers.     

Controlled release of local anesthetic from calcium phosphate bone cements

Novel lidocaine containing calcium phosphate bone cements have been developed. Lidocaine release kinetics of these cements have been evaluated.Calcium phosphate cements have a great potential for local drug delivery. Release of local anesthetic, such as lidocaine, at the implant site can be useful for reducing pain immediately after implantation.In this work a local anesthetic – lidocaine hydrochloride – was incorporated into α-tricalcium phosphate cement. Lidocaine release profile was dependent on cement components used. All cements were characterized by an initial burst release, which can be correlated with cement pH values, followed by gradual drug release. Drug release continued for up to 6 days and was slower, if cement pH was higher. Addition of lidocaine hydrochloride accelerated setting and changed microstructure of the set cement.     

Setting time and formability of calcium phosphate cements prepared using modified dicalcium phosphate anhydrous powders

Calcium phosphate cements (CPCs) were prepared using Ca₄(PO₄)₂O (TeCP) and modified CaHPO₄ (DCPA) to evaluate the effects of the powder properties for DCPA particles on the setting time and formability of the resulting CPCs. Two types of modified DCPA were prepared by milling commercially available DCPA with ethanol (to produce E-DCPA) or distilled water (to produce W-DCPA). The E-DCPA samples consisted of well-dispersed, fine primary particles, while the W-DCPA samples contained agglomerated particles, and had a smaller specific surface area. The mean particle size decreased with increased milling time in both cases. The raw CPC powders prepared using W-DCPA had a higher packing density than those prepared using E-DCPA, regardless of the mean particle size. The setting time of the CPC paste after mixing with distilled water decreased with decreases in the mean particle size and specific surface area, for both types of DCPA. The CPCs prepared using W-DCPA showed larger plasticity values compared with those prepared using E-DCPA, which contributed to the superior formability of the W-DCPA samples. The CPCs prepared using W-DCPA showed a short setting time and large plasticity values, despite the fact that only a small amount of liquid was used for the mixing of the raw CPC powders (a liquid-to-powder ratio of 0.25 g g^?1 was used). It is likely that the higher packing density of the raw CPC powders prepared using W-DCPA was responsible for the higher performance of the resulting CPCs.