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.     

Preparation and properties of calcium phosphate cements incorporated gelatin microspheres and calcium sulfate dihydrate as controlled local drug delivery system

To develop high macroporous and degradable bone cements which can be used as the substitute of bone repairing and drug carriers, cross-linked gelatin microspheres (GMs) and calcium sulfate dihydrate (CSD) powder were incorporated into calcium phosphate bone cement (CPC) to induce macropores, adjust drug release and control setting time of α-TCP–liquid mixtures after degradation of GMs and dissolution of CSD. In this study, CSD was introduced into CPC/10GMs composites to offset the prolonged setting time caused by the incorporation of GMs, and gentamicin sulphate (GS) was chosen as the model drug entrapped within the GMs. The effects of CSD amount on the cement properties, drug release ability and final macroporosity after GMs degradation were studied in comparison with CPC/GMs cements. The resulting cements presented reduced setting time and increased compressive strength as the content of CSD below 5 wt%. Sustained release of GS was obtained on at least 21 days, and release rates were found to be chiefly controlled by the GMs degradation rate. After 4 weeks of degradation study, the resulting composite cements appeared macroporous, degradable and suitable compressive strength, suggesting that they have potential as controlled local drug delivery system and for cancellous bone applications.     

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.     

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.     

Effect of temperature and immersion on the setting of some calcium phosphate cements

Calcium phosphate cements based on powders containing -Ca₃(PO₄)₂ and aqueous solutions containing Na₂HPO₄ as accelerator were used to determine the effects of accelerator concentration, temperature and immersion on the setting time. Increases in accelerator concentration and temperature increased the rate of setting, but immersion had a retarding effect. These results were used to design a method whereby a syringe filled with cement paste can be kept ready for injection of the paste into the implantation site for a long time, whereas setting of the cement paste in the body takes place in a short time.     

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.     

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.     

Fabrication and mechanical properties of calcium phosphate cements (CPC) for bone substitution

Calcium phosphate cements have been used in medical and dental applications for many years. However, their low strength and their high brittleness prohibit their use in many stress-bearing locations, which would require an improvement in mechanical properties. The influence of microstructural parameters on the latter has nevertheless barely been investigated in a systematic manner. To this aim, apatite cements have been fabricated through α-TCP (α-tricalcium phosphate) hydrolysis, and their mechanical properties have been measured (Young's modulus, fracture toughness and compressive strength), as a function of various parameters (particle size, liquid-to-powder ratio, amount and morphology of porosity, including macropores created by mannitol particles used as porogen). Five days following the mixing of phases, identification and microstructural observation indicated the presence of unreacted α-TCP particles, exhibiting very weak links with the apatite matrix and often surrounded by microcracks. The latter provoke a decrease in Young's modulus. The coarser the microstructure, the larger the critical flaw size causing fracture. In the case of macroporous materials, the critical flaw size increases with macroporosity. The knowledge gained should allow, in the end, to improve mechanical properties by controlling the microstructure, and to find a better compromise between strength and biological behaviour.     

Porous calcium phosphate ceramics prepared by coating polyurethane foams with calcium phosphate cements

Porous calcium phosphates have important biomedical applications such as bone defect fillers, tissue engineering scaffolds and drug delivery systems. While a number of methods to produce the porous calcium phosphate ceramics have been reported, this study aimed to develop a new fabrication method. The new method involved the use of polyurethane foams to produce highly porous calcium phosphate cements (CPCs). By firing the porous CPCs at 1200 °C, the polyurethane foams were burnt off and the CPCs prepared at room temperature were converted into sintered porous hydroxyapatite (HA)-based calcium phosphate ceramics. The sintered porous calcium phosphate ceramics could then be coated with a layer of the CPC at room temperature, resulting in high porosity, high pore interconnectivity and controlled pore size.     

Preparation and mechanical properties of calcium phosphate/copoly-L-lactide composites

New artificial bone materials were prepared using calcium phosphates, hydroxyapatite and -tricalicum phosphate, and copoly-L-lactide, CPLA. Calcium phosphate powder and CPLA were mixed at 453 K for 10 min with various mixing ratios. Scanning electron microscope observations indicated that the composites of -tricalicum phosphate and CPLA were homogeneously dispersed and highly adhesive. Youngs modulus of the composites was the same as bone, and bending strength was over half that of bone. The improvement of Youngs modulus compared to the original two materials was due to a composite effect. The composites are expected to be usable as artificial bone materials.     

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.     

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.     

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.     

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.     

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.