E. Fernández

Setting Reaction and Hardening of an Apatitic Calcium Phosphate Cement

The combination of self-setting and biocompatibility makes calcium phosphate cements potentially useful materials for a variety of dental applications. The objective of this study was to investigate the setting and hardening mechanisms of a cement-type reaction leading to the formation of calcium-deficient hydroxyapatite at low temperature. Reactants used were a-tricalcium phosphate containing 17 wt% β-tricalcium phosphate, and 2 wt% of precipitated hydroxyapatite as solid phase and an aqueous solution 2.5 wt% of disodium hydrogen phosphate as liquid phase. The transformation of the mixture was stopped at selected times by a freeze-drying technique, so that the cement properties at various stages could be studied by means of x-ray diffraction, infrared spectroscopy, and scanning electron microscopy. Also, the compressive strength of the cement was measured as a function of time. The results showed that: (1) the cement setting was the result of the a-tricalcium phosphate hydrolysis, giving as a product calcium-deficient hydroxyapatite, while β-tricalcium phosphate did not participate in the reaction; (2) the extent of conversion of a-TCP was nearly 80% after 24 hr; (3) both the extent of conversion and the compressive strength increased initially linearly with time, subsequently reaching a saturation level, with a strong correlation observed between them, indicating that the microstructural changes taking place as the setting reaction proceeded were responsible for the mechanical behavior of the cement; and (4) the microstructure of the set cement consisted of clusters of big plates with radial or parallel orientations in a matrix of small plate-like crystals.

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.

Compliance of an apatitic calcium phosphate cement with the short-term clinical requirements in bone surgery, orthopaedics and dentistry

An apatitic calcium phosphate cement was developed containing a nucleator in its powder and an accelerator in the liquid and having an initial setting time of 7.5 min and a final setting time of 12.5 min according to testing with Gillmore needles at room temperature. At body temperature the initial setting time is 6 min, after which the wound can be closed. The dough time (during which it can be deformed without damaging its microstructure) is 4 min. Therefore, the time lost during an operation with this material is 2 min. The product does not shrink or expand during setting, neither is there a thermal effect; it does not swell or disintegrate upon exposure to aqueous fluids after initial setting. Upon soaking in Ringers solution the product obtains a final compressive strength of 40 MPa and 65% of that strength is reached within 6 h at body temperature. Cytotoxicity is absent. Applications are envisaged in bone surgery, orthopaedics and dentistry, a.o. for acceleration of the osseointegration of metal endoprostheses.

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.

An ultrasonic pulse-echo technique for monitoring the setting of CaSO4-based bone cement

We present a new ultrasonic technique for monitoring the entire setting process of injectable bone cement. The problem with existing standards is their subjectivity. Because of this the results are not comparable between different research groups. A strong advantage with the proposed technique is that it is non-invasive and non-destructive, since no manipulation of the cement sample is needed once the measurement has started. Furthermore, the results are reproducible with small variations. The testing was performed on calcium sulfate cement using an ultrasonic pulse-echo approach. The results show that the acoustic properties of the cement are strongly correlated with the setting time, the density, and the adiabatic bulk modulus. The measured initial and final setting times agree well with the Gillmore needles standard. An important difference compared to the standards, is that the technique presented here allows the user to follow the entire setting process on-line.

Development of a method to measure the period of swelling of calcium phosphate cements

In the field of biomaterials the development of calcium phosphate cements dates back to 1983 [1]. Despite their good biocompatibility these biomaterials have seldom been used in animal and clinical trials. In our experience one of the properties that limits the applicability of calcium phosphate cements in animal and clinical trials is their swelling and superficial disintegration upon premature contact with blood or other body fluids. This property is comparable to the hygroscopic expansion of gypsum investments [2] or the increased solubility and disintegration of dental silicate cements and zinc phosphate cements [3] upon premature contact with water and saliva, respectively. The surgeon must therefore keep the field of operation free of blood or other body fluids during the whole period over which the calcium phosphate cement swells or disintegrates. Therefore, the property of swelling must be brought under control, before a calcium phosphate cement can be offered to clinicians for animal or clinical trials. The purpose of the present study was twofold: (i) to develop a method or methods to measure the period of swelling, and (ii) to observe whether the addition of a nucleator phase to the cement powder and/or that of an accelerator to the cement liquid can help to reduce the period of swelling. An apatitic calcium phosphate cement, developed in a previous study [4], was chosen for the present investigation. It contained alpha-tertiary calcium phosphate (a-TCP) as an active ingredient in its powder, to which particles of precipitated hydroxyapatite (PHA) were added, which functioned as a nucleator for the precipitation of calcium deficient hydroxyapatite (CDHA) formed during the setting reaction. Water was used as cement liquid, in which disodium hydrogen ph0sphate (Na2HPO4) could be dissolved to function as an accelerator of the setting reaction. Optimum milling conditions for the cement powder and an optimum of 0.32 wt% of liquid to powder were used [4]. The cement powders used contained either 2, 4 or 6 wt % PHA and the liquids either 0, 2, 3 or 4 wt % Na2HPO4. The initial (I) and final (F) setting times known to occur in the combinations studied are given in Table I. Adequate amounts of powder and liquid were mixed in a mortar for 1 min. Brass rings with internal diameter 9.3 mm and height 5.0 mm were filled with the cement mass, while resting on a glass plate. They were stored at room temperature in air until soaking was commenced. Soaking was carried out in Ringers solution at 37 °C. Immediately after soaking observation of any disintegration was done by visual inspection (method 1). After 30min of soaking the thickness of the cement mass was measured with a micrometer (while still held in the brass ring) and the diameter of the cement cylinder was determined (in this case, the cement mass was removed from the brass ring just prior to the

Osteogenic biphasic calcium sulphate dihydrate/iron-modified alpha-tricalcium phosphate bone cement for spinal applications: in vivo study.

In this study, the biocompatibility and the osteogenic features of a new iron-modified alpha-tricalcium phosphate (IM/alpha-TCP) and calcium sulphate dihydrate (CSD) biphasic cement (IM/alpha-TCP/CSD-BC) have been investigated in terms of the in vivo cement resorption, bone tissue formation and host tissue response on sheep animal model. Histological evaluation performed on undecalcified cement-bone specimens assessed the in vivo behaviour. It has been shown that the new IM/alpha-TCP/CSD-BC has the ability to produce firm bone binding in vivo (i.e. bioactivity). Qualitative histology proved cement biocompatibility, osteoconduction and favourable resorption, mainly through a macrophage-mediated mechanism. The results showed that the new cements have biocompatible and osteogenic features of interest as possible cancellous bone replacement biomaterial for minimally invasive spinal surgery applications.

Design and properties of 3D scaffolds for bone tissue engineering.

UNLABELLED In this study, the Voronoi tessellation method has been used to design novel bone like three dimension (3D) porous scaffolds. The Voronoi method has been processed with computer design software to obtain 3D virtual isotropic porous interconnected models, exactly matching the main histomorphometric indices of trabecular bone (trabecular thickness, trabecular separation, trabecular number, bone volume to total volume ratio, bone surface to bone volume ratio, etc.). These bone like models have been further computed for mechanical (elastic modulus) and fluid mass transport (permeability) properties. The results show that the final properties of the scaffolds can be controlled during their microstructure and histomorphometric initial design stage. It is also shown that final properties can be tuned during the design stage to exactly match those of trabecular natural bone. Moreover, identical total porosity models can be designed with quite different specific bone surface area and thus, this specific microstructural feature can be used to favour cell adhesion, migration and, ultimately, new bone apposition (i.e. osteoconduction). Once the virtual models are fully characterized and optimized, these can be easily 3D printed by additive manufacturing and/or stereolitography technologies. STATEMENT OF SIGNIFICANCE The significance of this article goes far beyond the specific objectives on which it is focussed. In fact, it shows, in a guided way, the entire novel process that can be followed to design graded porous implants, whatever its external shape and geometry, but internally tuned to the exact histomorphometric indices needed to match natural human tissues microstructures and, consequently, their mechanical and fluid properties, among others. The significance is even more relevant nowadays thanks to the available new computing and design software that is easily linked to the 3D printing new technologies. It is this transversality, at the frontier of different disciplines, the main characteristic that gives this article a high scientific impact and interest to a broaden audience.

Monitoring the setting of calcium-based bone cements using pulse-echo ultrasound.

We present a new technique, based on pulse-echo ultrasound, for monitoring the entire setting process of injectable bone cement. This research has been motivated by the lack of satisfying standards. The main problem with existing standards is the subjectivity, which leads to poor reproducibility. Because of this the results are not comparable between different research groups. A strong advantage with the proposed technique is that if low-intensity ultrasound is used, it provides a non-destructive analysis method. Once the cement paste has been applied to the measurement cell, no manipulation is needed throughout the entire setting process. The problem of the ultrasound affecting the setting of certain cement materials has been investigated, and solutions are discussed. The propagation of ultrasound is temperature-dependent, and therefore a technique for automatic compensation for temperature variations is discussed briefly. The testing was performed on α-calcium sulfate hemihydrate (CSH) and mixtures of CSH and α-tricalcium phosphate (α-TCP). The results show that the acoustic properties of the cement are strongly correlated with the setting time, the density, and the adiabatic bulk modulus. The measured initial and final setting times agree well with the Gillmore needles standard. An important difference compared to the standards, is that the technique presented here allows the user to follow the entire setting process on-line.

Common ion effect on some calcium phosphate cements

Abstract Four calcium phosphate cements were selected to investigate whether the use of aqueous solutions of CaCl2, Na2HPO4 or NaH2PO4.2H2O instead of water had any effect on their properties. One cement was sensitive for the CaCl2 solution, two others for the phosphate solutions, and the fourth cement was insensitive to all three solutions. The setting times were reduced considerably. However, the strength values after soaking the cements in Ringers solution for 1 day at 37°C decreased with the use of an accelerator. The use of phosphate solutions changed the pH of the cement slurry slightly during setting, whereas the CaCl2 solution had no effect on the pH.