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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Hydrothermal light-weight calcium phosphate cements: use of polyacrylnitrile-shelled hollow microspheres

Calcium phosphate cement (CPC) slurries with a very low density of less than 1.0 g cm-3 were prepared by incorporating polyacrylnitrile (PAN)-shelled hollow microspheres with calcite sizing into CPC pastes consisting of sodium metaphosphate, high alumina cement and water. Their characterizations were then investigated to assess their value as light-weight CPC cementing materials for use in geothermal wells at hydrothermal temperatures up to 300°C. This light-weight cement showed the following four main features: firstly the chemical inertness of the PAN shells to CPC served to extend thickening time of the slurry; secondly the microsphere surfaces preferentially absorbed Al ions from among the various ionic species in the interstitial fluid of CPC at 100°C, thereby forming amorphous Al-enriched sodium phosphate hydrates as interfacial intermediate layers which tightly linked the microspheres to the CPC matrix; thirdly although the thermal decomposition of PAN shells around 200°C generated numerous voids in the cement body, these open spaces were filled by well-grown wardite crystals formed by the in-situ phase transformation of amorphous sodium aluminate phosphate hydrates, thereby preventing a serious loss in strength of the light-weight calcium phosphate cement (LCPC) specimens; fourthly the major phase composition of CPC matrix at 200 and 300°C consisted of well-crystallized hydroxyapatite and boehmite compounds which can be categorized as alkali carbonation-resistant phases. The integration of these characteristics was responsible for maintaining the compressive strength of greater than 0.6 MPa for LCPC specimens derived from a very-low-density (0.98 g cm-3) slurry exposed for 6 months to a 0.05 M Na2CO3-laden solution at 250°C.     

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.     

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     

In vivo estimation of calcium phosphate cements containing chondroitin sulfate in subcutis

Calcium phosphate cements using an equimolar mixture of tetracalcium phosphate and dicalcium phosphate dihydrate (TeDCPD) for the powder phase were experimentally developed for use in endodontic treatment. The fundamental cement is comprised of TeDCPD kneaded with modified McIlvain's buffer solution containing calboxymethyl cellulose sodium salt (CEM-1). In the liquid phase of the modified one (CEM-2), chondroitin sulfate (CS) was added in place of the salt. The final concentration of CS in CEM-2 is 1%. Another one (CEM-3) contained 2% CS finally in place of the salt. X-ray diffract meter (XRD) was used to examine the crystalline phases of the cements. The tissue compatibility of the cements was examined histologically in the subcutaneous tissue using rats. The XRD results showed no dibasic calcium phosphate phase to be traced in CS containing two cements after 1 day of kneading. There were more multinucleated giant cells appearing around CEM-1 than around CEM-2 or CEM-3 after 4 weeks. Fibroblasts, collagen fibers and small vessels infiltrated into the internal porous structure of CEM-3. Excluding CEM-3, two cements were encapsulated with a dense fibrous connective tissue layer. We conclude that CS, in the experimentally developed cement, contributed to biocompatibility and bioactivity of the cement.     

Enhancing the performance of calcium sulfoaluminate blended cements with shrinkage reducing admixture or lightweight sand

This study investigates the effect of using shrinkage reducing admixture (SRA) or lightweight sand (LWS) on enhancing the performance of calcium sulfoaluminate (CSA) cement in combination with ordinary Portland cement (OPC). Of special interest is the efficacy of the SRA or LWS in modifying the expansion/shrinkage and compressive strength characteristics of OPC-CSA systems in the absence of adequate duration of water curing, which is critical for the expansive reaction of CSA cement and its ability to mitigate shrinkage. Hydration kinetics, autogenous and drying deformation, thermogravimetry, and scanning electron microscopy (SEM) are used to evaluate the effect of SRA or LWS on the performance of the OPC-CSA systems. Test results indicate that the OPC-CSA system can exhibit similar drying shrinkage to that of the plain OPC mixture when no moist curing is applied. In the presence of LWS or SRA, the OPC-CSA systems exhibited lower shrinkage or higher extent of expansion compared to the corresponding OPC-CSA mixture alone. This is attributed to delay of the drop in internal relative humidity and promoting hydration of the OPC-CSA system which can enhance the ettringite-generating potential of CSA cement. The use of LWS was found to be highly effective in enhancing compressive strength of OPC-CSA system. SEM results at 91 days confirm the higher density and lower porosity for the paste surrounding LWS particles compared to the corresponding mixture made without LWS. In the case of inadequate moist curing, the presence of LWS or SRA is shown to enhance the overall performance of OPC-CSA system. For a given overall desirability value of 0.65 determined by multi-objective optimization, the incorporation of 1% SRA or 10% LWS was found to enable the reduction the required period of moist curing from 6 days to 5 and 3 days, respectively.     

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.     

Calcium phosphate bone cements

The principles of developing calcium phosphate cements (CPCs) for replacement and regeneration of bone tissue are considered. The basic classification of CPCs is given according to the phase composition of the reaction products in the setting systems. Processes of phase composition and development of microstructure and properties are discussed. Injectable CPC compositions are considered, and the factors affecting the injectability, as well as the ways to modify the cement pastes to improve their properties, are discussed. The results of research and development in the field of composite CPCs, including those reinforced by disperse phases, are described. In the final part of the review, some data on commercial CPCs and their biological behavior are presented.     

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.