Search

Mesoporous hydroxyapatite (HA) is widely used in various applications, such as the biomedical field, as a catalytic, as a sensor, and many others. The aim of this work was to obtain HA powders by means of chemical precipitation in a medium containing a polymer-polyvinyl alcohol or polyvinylpyrrolidone (PVP)-with concentrations ranging from 0 to 10%. The HA powders were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, atomic emission spectroscopy with inductively coupled plasma, electron paramagnetic resonance, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The specific surface area (SSA), pore volume, and pore size distributions were determined by low-temperature nitrogen adsorption measurements, and the zeta potential was established. The formation of macropores in powder agglomerates was determined using SEM and TEM. The synthesis in 10% PVP increased the SSA from 101.3 to 158.0 m 2 /g, while the ripening for 7 days led to an increase from 112.3 to 195.8 m 2 /g, with the total pore volume rising from 0.37 to 0.71 cm 3 /g. These materials could be classified as meso-macroporous HA. Such materials can serve as the basis for various applications requiring improved textural properties and may lay the foundation for the creation of bulk 3D materials using a technique that allows for the preservation of their unique pore structure.

The development of magnesium calcium phosphate bone cements (MCPCs) has garnered substantial attention. MCPCs are bioactive and biodegradable and have appropriate mechanical and antimicrobial properties for use in reconstructive surgery. In this study, the cement powders based on a (Ca + Mg)/P = 2 system doped with Zn 2+ at 0.5 and 1.0 wt.% were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behavior of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn 2+ 1.0 wt.%-substituted powders. Zn 2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter of up to 8 mm. Biological assays confirmed that the developed cement is cytocompatible and promising as a potential bone substitute in reconstructive surgery.

Bone grafts with a high potential for osseointegration, capable of providing a complete and effective regeneration of bone tissue, remain an urgent and unresolved issue. The presented work proposes an approach to develop composite biomimetic bone material for reconstructive surgery by deposition (remineralization) on the surface of high-purity, demineralized bone collagen matrix calcium phosphate layers. Histological and elemental analysis have shown reproduction of the bone tissue matrix architectonics, and a high-purity degree of the obtained collagen scaffolds; the cell culture and confocal microscopy have demonstrated a high biocompatibility of the materials obtained. Adsorption spectroscopy, scanning electron microscopy, microcomputed tomography (microCT) and infrared spectroscopy, and X-ray diffraction have proven the efficiency of the deposition of calcium phosphates on the surface of bone collagen scaffolds. Cell culture and confocal microscopy methods have shown high biocompatibility of both demineralized and remineralized bone matrices. In the model of heterotopic implantation in rats, at the term of seven weeks, an intensive intratrabecular infiltration of calcium phosphate precipitates, and a pronounced synthetic activity of osteoblast remodeling and rebuilding implanted materials, were revealed in remineralized bone collagen matrices in contrast to demineralized ones. Thus, remineralization of highly purified demineralized bone matrices significantly enhanced their osteostimulating ability. The data obtained are of interest for the creation of new highly effective osteoplastic materials for bone tissue regeneration and augmentation.

Mesoporous hydroxyapatite (HA) materials demonstrate advantages as catalysts and as support systems for catalysis, as adsorbent materials for removing contamination from soil and water, and as nanocarriers of functional agents for bone-related therapies. The present research demonstrates the possibility of the enlargement of the Brunauer-Emmett-Teller specific surface area (SSA), pore volume, and average pore diameter via changing the synthesis medium and ripening the material in the mother solution after the precipitation processes have been completed. HA powders were investigated via chemical analysis, X-ray diffraction analysis, Fourier-transform IR spectroscopy, transmission electron microscopy (TEM), and scanning (SEM) electron microscopy. Their SSA, pore volume, and pore-size distributions were determined via low-temperature nitrogen adsorption measurements, the zeta potential was established, and electron paramagnetic resonance (EPR) spectroscopy was performed. When the materials were synthesized in water-ethanol and water-acetone media, the SSA and total pore volume were 52.1 m 2 g -1 and 116.4 m 2 g -1 , and 0.231 and 0.286 cm 3 g -1 , respectively. After ripening for 21 days, the particle morphology changed, the length/width aspect ratio decreased, and looser and smaller powder agglomerates were obtained. These changes in their characteristics led to an increase in SSA for the water and water-ethanol samples, while pore volume demonstrated a multiplied increase for all samples, reaching 0.593 cm 3 g -1 for the water-acetone sample.

Gadolinium-containing calcium phosphates are promising contrast agents for various bioimaging modalities. Gadolinium-substituted tricalcium phosphate (TCP) powders with 0.51 wt% of gadolinium (0.01Gd-TCP) and 5.06 wt% of (0.1Gd-TCP) were synthesized by two methods: precipitation from aqueous solutions of salts (1) (Gd-TCP-pc) and mechano-chemical activation (2) (Gd-TCP-ma). The phase composition of the product depends on the synthesis method. The product of synthesis (1) was composed of β -TCP (main phase, 96%), apatite/chlorapatite (2%), and calcium pyrophosphate (2%), after heat treatment at 900 °C. The product of synthesis (2) was represented by β -TCP (main phase, 73%), apatite/chlorapatite (20%), and calcium pyrophosphate (7%), after heat treatment at 900 °C. The substitution of Ca 2+ ions by Gd 3+ in both β -TCP (main phase) and apatite (admixture) phases was proved by the electron paramagnetic resonance technique. The thermal stability and specific surface area of the Gd-TCP powders synthesized by two methods were significantly different. The method of synthesis also influenced the size and morphology of the prepared Gd-TCP powders. In the case of synthesis route (1), powders with particle sizes of tens of nanometers were obtained, while in the case of synthesis (2), the particle size was hundreds of nanometers, as revealed by transmission electron microscopy. The Gd-TCP ceramics microstructure investigated by scanning electron microscopy was different depending on the synthesis route. In the case of (1), ceramics with grains of 1-50 μm, pore sizes of 1-10 µm, and a bending strength of about 30 MPa were obtained; in the case of (2), the ceramics grain size was 0.4-1.4 μm, the pore size was 2 µm, and a bending strength of about 39 MPa was prepared. The antimicrobial activity of powders was tested for four bacteria ( S. aureus , E. coli , S. typhimurium , and E. faecalis ) and one fungus ( C . albicans ), and there was roughly 30% of inhibition of the micro-organism's growth. The metabolic activity of the NCTC L929 cell and viability of the human dental pulp stem cell study demonstrated the absence of toxic effects for all the prepared ceramic materials doped with Gd ions, with no difference for the synthesis route.

Octacalcium phosphate (OCP, Ca 8 H 2 (PO 4 ) 6 ·5H 2 O) is known to be a possible precursor of biological hydroxyapatite formation of organic bone tissue. OCP has higher biocompatibility and osseointegration rate compared to other calcium phosphates. In this work, the synthesis of low-temperature calcium phosphate compounds and substituted forms of those at physiological temperatures is shown. Strontium is used to improve bioactive properties of the material. Strontium was inserted into the OCP structure by ionic substitution in solutions. The processes of phase formation of low-temperature OCP with theoretical substitution of strontium for calcium up to 50 at.% in conditions close to physiological, i.e., temperature 35-37 °C and normal pressure, were described. The effect of strontium substitution range on changes in the crystal lattice of materials, the microstructural features, surface morphology and biological properties in vitro has been established. The results of the study indicate the effectiveness of using strontium in OCP for improving biocompatibility of OCP based composite materials intended for bone repair.

The development of new materials with antibacterial properties and the scope to decrease or eliminate the excessive antibiotic use is an urgent priority due to the growing antibiotic resistance-related mortalities. New bone substitute materials with intrinsic antibacterial characteristics are highly requested for various clinical applications. In this study, the choice of copper ions as substitutes for calcium in tricalcium phosphate (TCP) has been justified by their pronounced broad-spectrum antibacterial properties. Copper-substituted TCP (Cu-TCP) ceramics with the copper content of 1.4 and 0.1 wt% were synthesized by mechano-chemical activation. X-ray diffraction (XRD) analyses established that both pure and copper-containing compounds adopted the structure of whitlockite (β-TCP). XRD and electron paramagnetic resonance (EPR) spectroscopy revealed the partial isovalent substitution of calcium ions with copper ions in the β-TCP lattice. With the use of infrared and EPR spectroscopies, it was detected that carbonate ions got incorporated into the β-TCP structure during the synthesis procedure. By releasing the tension in the M(5)O6 octahedron consequential to the lower CaO bond length than the corresponding sum of ionic radii, the substitution of calcium with smaller copper ions stabilizes the structure of β-TCP. As concluded form the thermal analyses, the introduction of Cu prevented the polymorphic transformation of β- to α-TCP. At the same time, the introduction of Cu to the β-TCP structure enhanced the crystal growth and porosity of the ceramics, which had a positive effect on the cytocompatibility of the material. The MTT colorimetric assay showed that the metabolic activity of the mouse fibroblast NCTC L929 cell line during 24 h of incubation with 3-day extracts from Cu-TCP (1.4 wt%) and β-TCP pellets in the cell culture medium was similar to the negative control, indicating the absence of any inhibitory effects on cells. The seeding and the growth of human dental pulp stem cells on the surface of Cu-TCP (1.4 wt%) and β-TCP ceramics also showed the absence of any signs of cytotoxicity. Finally, microbiological assays demonstrated the antibacterial activity of Cu-TCP ceramics against Escherichia coli and Salmonella enteritidis, whereas β-TCP did not exhibit such an activity. Overall, the addition of Cu ions to β-TCP improves its antibacterial properties without diminishing the biocompatibility of the material, thus making it more attractive than pure β-TCP for clinical applications such as synthetic bone grafts and orthopaedic implant coatings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

For bone replacement materials, osteoconductive, osteoinductive, and osteogenic properties are desired. The bacterial resistance and the need for new antibacterial strategies stand among the most challenging tasks of the modern medicine. In this work, brushite cements based on powders of Zinc (Zn) (1.4 wt%) substituted tricalcium phosphate (β-TCP) and non-substituted β-TCP were prepared and investigated. Their initial and final phase composition, time of setting, morphology, pH evolution, and compressive strength are reported. After soaking for 60 days in physiological solution, the cements transformed into a mixture of brushite and hydroxyapatite. Antibacterial activity of the cements against Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa bacteria strains was attested. The absence of cytotoxicity of cements was proved for murine fibroblast NCTC L929 cells. Moreover, the cell viability on the β-TCP cement containing Zn 2+ ions was 10% higher compared to the β-TCP cement without zinc. The developed cements are perspective for applications in orthopedics and traumatology., (© 2021. The Author(s).)

Mesoporous hydroxyapatite (HA) and iron(III)-doped HA (Fe-HA) are attractive materials for biomedical, catalytic, and environmental applications. In the present study, the nanopowders of HA and Fe-HA with a specific surface area up to 194.5 m 2 /g were synthesized by a simple precipitation route using iron oxalate as a source of Fe 3+ cations. The influence of Fe 3+ amount on the phase composition, powders morphology, Brunauer-Emmett-Teller (BET) specific surface area (S), and pore size distribution were investigated, as well as electron paramagnetic resonance and Mössbauer spectroscopy analysis were performed. According to obtained data, the Fe 3+ ions were incorporated in the HA lattice, and also amorphous Fe oxides were formed contributed to the gradual increase in the S and pore volume of the powders. The Density Functional Theory calculations supported these findings and revealed Fe 3+ inclusion in the crystalline region with the hybridization among Fe-3d and O-2p orbitals and a partly covalent bond formation, whilst the inclusion of Fe oxides assumed crystallinity damage and rather occurred in amorphous regions of HA nanomaterial. In vitro tests based on the MG-63 cell line demonstrated that the introduction of Fe 3+ does not cause cytotoxicity and led to the enhanced cytocompatibility of HA.

Octacalcium phosphate (OCP), a new-generation bone substitute material, is a considered precursor of the biological bone apatite. The two-layered structure of OCP contains the apatitic and hydrated layers and is intensively involved in ion-exchange surface reactions, which results in OCP hydrolysis to hydroxyapatite and adsorption of ions or molecular groups presented in the environment. During various in vitro procedures, such as biomaterial solubility, additive release studies, or the functionalization technique, several model solutions are applied. The composition of the environmental solution affects the degree and rate of OCP hydrolysis, its surface reactivity, and further in vitro and in vivo properties. The performed study was aimed to track the structural changes of OCP-based materials while treating in the most popular model solutions of pH values 7.2-7.4: simulated body fluid (SBF), Dulbecco's phosphate-buffered saline (DPBS), supersaturated calcification solution (SCS), normal saline (NS), and Dulbecco's modified Eagle's medium (DMEM). Various degrees of OCP hydrolysis and/or precipitate formation were achieved through soaking initial OCP granules in the model solutions. Detailed data of X-ray diffraction, Fourier-transform infrared spectroscopy, atomic emission spectrometry with inductively coupled plasma, and scanning electron microscopy are presented. Cultivation of osteosarcoma cells was implemented on OCP pre-treated in DMEM for 1-28 days. It was shown that NS mostly degraded the OCP structure. DPBS slightly changed the OCP structure during the first treatment term, and during further terms, the crystals got thinner and OCP hydrolysis took place. Treatment in SBF and SCS caused the precipitate formation along with OCP hydrolysis, with a larger contribution of SCS solution to precipitation. Pre-treating in DMEM enhanced the cytocompatibility of materials. As a result, on performing the in vitro procedures, careful selection of the contact solution should be made to avoid the changes in materials structure and properties and get adequate results., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Bioactive manganese (Mn)-doped ceramic coatings for intraosseous titanium (Ti) implants are developed. Arc plasma deposition procedure is used for coatings preparation. X-ray Diffraction, Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy, and Electron Paramagnetic Resonance (EPR) methods are applied for coatings characterization. The coatings are homogeneous, composed of the main phase α-tricalcium phosphate (α-TCP) (about 67%) and the minor phase hydroxyapatite (about 33%), and the Mn content is 2.3 wt%. EPR spectroscopy demonstrates that the Mn ions are incorporated in the TCP structure and are present in the coating in Mn 2+ and Mn 3+ oxidation states, being aggregated in clusters. The wetting contact angle of the deposited coatings is suitable for cells' adhesion and proliferation. In vitro soaking in physiological solution for 90 days leads to a drastic change in phase composition; the transformation into calcium carbonate and octacalcium phosphate takes place, and no more Mn is present. The absence of antibacterial activity against Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa bacteria strains is observed. A study of the metabolic activity of mouse fibroblasts of the NCTC L929 cell line on the coatings using the MTT (dye compound 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test demonstrates that there is no toxic effect on the cell culture. Moreover, the coating material supports the adhesion and proliferation of the cells. A good adhesion, spreading, and proliferative activity of the human tooth postnatal dental pulp stem cells (DPSC) is demonstrated. The developed coatings are promising for implant application in orthopedics and dentistry.

Calcium phosphate cements are of great interest for researchers and their applications in medical practice expanded. Nevertheless, they have a number of drawbacks including the insufficient level of mechanical properties and low degradation rate. Struvite (MgNH 4 PO 4 ) -based cements, which grew in popularity in recent years, despite their neutral pH and acceptable mechanical performance, release undesirable NH 4 + ions during their resorption. This issue could be avoided by replacement of ammonia ions in the cement liquid with sodium, however, such cements have a pH values of 9-10, leading to cytotoxicity. Thus, the main goal of this investigation is to optimize the composition of cements to achieve the combination of desirable properties: neutral pH, sufficient mechanical properties, and the absence of cytotoxicity, applying Na 2 HPO 4 -based cement liquid. For this purpose, cement powders precursors in the CaO-MgO-P 2 O 5 system were synthesized by one-pot process in a wide composition range, and their properties were investigated. The optimal performance was observed for the cements with (Ca + Mg)/P ratio of 1.67, which are characterized by newberyite phase formation during setting reaction, pH values close to 7, sufficient compressive strength up to 22 ± 3 MPa (for 20 mol.% of Mg), dense microstructure and adequate matrix properties of the surface. This set of features make those materials promising candidates for medical applications., Competing Interests: The authors declare no conflicts of interest., (© 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Bioceramics are used to treat bone defects but in general do not induce formation of new bone, which is essential for regeneration process. Many aspects related to bioceramics synthesis, properties and biological response that are still unknown and, there is a great need for further development. In the most recent research efforts were aimed on creation of materials from biological precursors of apatite formation in humans. One possible precursor is octacalcium phosphate (OCP), which is believed to not only exhibit osteoconductivity but possess osteoinductive quality, the ability to induce bone formation. Here we propose a relatively simple route for OCP ceramics preparation with a specifically designed microstructure. Comprehensive study for OCP ceramics including biodegradation, osteogenic properties in ortopic and heterotopic models and limited clinical trials were performed that demonstrated enhanced biological behavior. Our results provide a possible new concept for the clinical applications of OCP ceramics.

Various calcium phosphate ceramic materials were created and their effect on cultured mesenchymal cells from exfoliated deciduous tooth pulp was evaluated. Tricalcium phosphate ceramics provides best cell survival and is an optimal material for bone tissue engineering. Analysis of the effects of tricalcium phosphate ceramics on osteogenic differentiation of SHED cells suggests that this material potentiated dexamethasone-induced osteogenic differentiation, which manifested in the increased number of ossification foci and enhanced extracellular matrix production by cells. Thus, the tricalcium phosphate ceramics created by us is a promising biomedical material that can be used for tissue-engineered bone analogs.

In this study, the phase development in the cement system α-TCP-OCP with phosphoric acid as a setting liquid was studied. The most promising formulation of α-TCP (60 wt%) and OCP (40 wt%) is proposed. This cement has the following characteristics: setting time 10 min, pH = 6.7, the compressive strength about 30 MPa, and high dissolution rate in an isotonic solution; the final wt% composition of α-TCP/DCPD/HA/OCP equals 27/38/20/15. Energy dispersive X-ray diffraction techniques were used for in situ monitoring of the processes taking place in the cement in real time.

In this study, the real-time monitoring of structural changes, occurring upon poorly crystalline apatite bone cement hardening in the presence of chitosan, simulated body fluid and human blood, was performed. Strong experimental evidence of octacalcium phosphate intermediate phase is provided. The energy dispersive X-ray diffraction was applied in situ to monitor the structural changes upon the transformation process, while the Fourier transform infrared spectroscopy and the scanning electron microscopy supplied information on the vibrational and morphological properties of the system. The cooperative action of chitosan and simulated body fluid induces the formation of a preferentially oriented hydroxyapatite phase, this process being similar to the oriented self-assembling process in collagen-apatite matrix in human plasma, occurring upon in vivo biomineralization. Conversely, the presence of blood does not induce any significant change in hardening kinetics and the final structure of the investigated cement.

Despite the numerous literature data available in the field of calcium phosphate bone cements, the mechanism and kinetics of their hardening, both of which are of great importance for cements application, in most cases, is unknown. In this work, the mechanism and kinetics of hardening of two novel high-strength calcium phosphate bone cements were studied using the energy dispersive X-ray diffraction technique, which allows rapid collection of the patterns. The phase transformations occurring on the setting and hardening processes were monitored in situ. Containing minimal quantity of components, whose mixing leads to the formation of cements with pH close to neutral, the cements under study are simple in handling. The main component of both formulations is tetracalcium phosphate. In both cements, the effect of the addition of high- and low-molecular weight chitosan on phase development and kinetics was investigated in detail. One of the cements has the compressive strength of about 70 MPa, whereas the strength of the other, containing Ca(3)Al(2)O(6), is much higher, about 100 MPa. This latter cement could be regarded as an alternative to the common low-strength bioresorbable brushite cements.

In this work, an anomalous microscopic and macroscopic behavior during the hardening process of a calcium phosphate cement, based on anhydrous dicalcium phosphate, was observed. Indeed, the standard compressive strength measurements provided completely unexpected results, which encouraged a deeper investigation by means of X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron and atomic force microscopies. The energy dispersive X-ray diffraction mode was preferred to the conventional angular dispersive one, the former being particularly suitable for the real-time studies, allowing us to follow the hardening process in situ and to confirm that the investigated cement undergoes a long-time crystallization much more complex than expected. Indeed, the sequence of diffraction patterns exhibited anomalous intensity modulations (corresponding to structural changes taking place upon hardening) being consistent, and even in phase, with the variations of the compressive strength. These anomalous intensity modulations were confirmed also by the in situ time-resolved Fourier transform infrared spectroscopy. The explanation of the anomalous behavior was given by means of a multiscale approach correlating the microscopic (structural) and macroscopic (compressive strength) properties. In perspective, this finding may be interesting not only from the fundamental materials science point of view, but also for novel applications. For example, it might be utilized as an "intrinsic bioreactor", playing the role of stimulator of cellular proliferation by exerting stresses due to its alternative contracting and expanding internal forces on the tissues.

Review of the literature and our own investigations describes structure, synthesis, hydrolysis, participation in biomineralisation of bone and teeth of octacalcium phosphate, a new synthetic bone scaffold.

Carbonated hydroxyapatite (CHA)-coated titanium can find wide applications as bone substitute implant in bone and dental surgery and orthopedics, promoting osseointegration with a host bone and ensuring biocompatibility and bioactivity. In this work, carbonated hydroxyapatite films were prepared on titanium substrates by pulsed laser deposition at different substrate temperatures ranging from 30 to 750 degrees C. The properties of films were investigated by scanning electron microscopy, atomic force microscopy, energy-dispersive X-ray diffraction, and Fourier transform infrared spectroscopy. Vickers microhardness measurements of the composite film-substrate systems were performed, and the intrinsic hardness of films was separated from the composite hardness using a "law-of-mixtures" approach and taking into account the indentation size effect. The prepared CHA films are nearly stoichiometric with a Ca/P atomic ratio of 2.0-2.2. The films deposited in the 30-500 degrees C temperature range are about 9 microm thick, amorphous, having an average roughness of 60 nm. At higher temperature, 700-750 degrees C, the films are about 4 microm thick, show a finer surface morphology and an average roughness of 20 nm. At 750 degrees C the films are amorphous, whereas at 700 degrees C they are crystalline and textured along the (202) and (212) directions. The intrinsic hardness of the films increased with an increase in substrate temperature, being as low as 5 GPa at 30 degrees C and reaching a high value of 28 GPa at 700 degrees C. The rich information gained by the joint use of the mentioned techniques allowed a comprehensive characterization of this system.

The aim of this work was to study the phase transformation during the setting reaction of two calcium phosphate bone cements based on either alpha tricalcium phosphate (alpha-TCP) or tetracalcium phosphate (TetCP) initial solid phase, and a magnesium carbonate-phosphoric acid solution as the hardening liquid. Low molecular weight (38.2 kDa) chitosan was used to retard the cement's setting reaction. To follow the kinetics of the phase development, an energy dispersive X-ray diffraction technique was applied. This technique allowed the collection of diffraction patterns from the cement pastes in situ starting from 1 min of the setting process. In the case of the TetCP-based cement, the appearance and evolution of an intermediate phase was detected.

Biocompatibility of porous granulated bioceramic materials (hydroxyapatite, beta-tricalcium phosphate, hydroxyapatite-b-tricalcium phosphate complex (80:20 wt%), carbonate-containing hydroxyapatite, and silicon-containing hydroxyapatite) was shown in a subcutaneous test on BDF1 mice. Dynamic (up to 8 months) observation showed gradual replacement of the granular substance with de novo forming bone tissue with hemopoiesis foci on a model of fenestral defect in the shin bone in Wistar rats. By the rate of resorption, the materials rank as follows: silicon-containing hydroxyapatite

We performed in vitro screening of monophasic (hydroxyapatite, beta-tricalcium phosphate, carbonate-substituted hydroxyapatite with 0.59 and 5.9 wt% substitution with CO(3)(2-)) and biphasic (hydroxyapatite-tricalcium phosphate with various percentage of the components 80/20, 60/40, 20/80, silicon-substituted hydroxyapatite with 0.79 wt% SiO(2)) porous granulated ceramics composed of calcium phosphate powders synthesized by methods of heterophasic interaction of reagents and precipitation from aqueous solutions using MTT test and cultured human fibroblasts. Acute toxicity of materials (24-h incubation with cell culture) and matrix properties (3, 5, 7, 14, 18, 21, 28 days in culture) were evaluated. We selected a batch of materials obtained by precipitation from aqueous solutions, which were non-toxic and were characterized by good matrix properties (for cells). Biphasic ceramics with hydroxyapatite-tricalcium phosphate ratio of 80/20 exhibited best characteristics, and ceramics on the basis of silicon-substituted hydroxyapatite showed moderate characteristics.

Synthetic carbonated apatite ceramics are considered as promising alternative to auto- and allograft materials for bone substitute. The aim of this study was to investigate the thermal stability of an AB-type carbonated apatite in the wide temperature range. The data on the thermal stability have to allow the conditions of the sintering of the ceramics to be controlled. Initial carbonated apatite powders were prepared by interaction between calcium oxide and ammonium hydrogen phosphate with addition of ammonium carbonate. Decomposition process was monitored by infra red spectroscopy, weight loss and X-ray diffraction of solid, and by infra red analysis of condensed gas phase resulted from the thermal decomposition of the sample in equilibrium conditions. Features of carbon monoxide and carbon dioxide release were revealed. The synthesized AB-type carbonated apatite is started to decompose at about 400 degrees Celsius releasing mainly carbon dioxide, but retained some carbonate groups and apatite structure at the temperature 1100 degrees Celsius useful to prepare porous carbonate-apatite ceramics intended for bone tissue engineering scaffolds.

In vivo and in vitro experiments on the application of cell technologies to tissue defect closure were conducted; autologic mesenchymal stem cells on 3-demensional matrices were used. The authors analyze the results of the application of bioengineering tissue equivalents for the closure of soft tissue and upper airway defects after extensive resections performed in 52 oncological patients. Tissue equivalents with stem cells provide engraftment and long-term graft functioning; they also modify wound surface, thus stimulating wound epithelization. In this study the application of tissue equivalents led to wound healing and functional recovery in 87% of patients.

In laboratory research there were studied different combinations of remineralizing agents allowing production of substances close by chemical composition to hydroxyapatite of hard dental tissues. The most acceptable for practical use in case of demineralizing foci of hard dental tissues treatment can be only 2 calcium orthophosphates that may be synthesized under physiological conditions from solutions of calcium nitrate and twice-substituted ammonium phosphate, in particular, dicalcium phosphate dihydrate (structure of brushite, CaHP0(4) x 2H(2)O) and the so called precipitated hydroxyapatite (Ca(10-x) (HPO(4))(x)(PO(4))(6-x)(OH)(2-x)). The data are the bases for development of remineralizing agents and their further experimental and clinical studies.

Calcium phosphate coatings are known to enhance long-term fixation, reliability and promote osteointegration of cementless titanium-based implant devices. This study was aimed at the pulsed laser deposition of calcium phosphate coatings onto titanium using hydroxyapatite and hydroxyapatite-fluorapatite targets. The deposition was carried out at the high laser beam fluence conditions, about 12 J/cm(2). The coatings were characterized with respect to their morphology, phase composition and hardness. X-ray energy dispersive analysis revealed the coatings retain their elemental composition, and fluoride content within the film is the same as in the initial target. However, unlike sintered targets, the deposited films contain no apatite-like phases. The hardness of the films, about 18 GPa, is surprisingly high compared to that of hydroxyapatite and hydroxyapatite-fluorapatite ceramic targets. The deposited coatings of 2.7-2.9 microm thickness have uniform and dense microstructure, containing the solidified droplets of the expulsed from the target phase. The uncommon structure and hardness of the films can be attributed to the melting and phase decomposition of the initial material in the laser plasma.

The mineral constituent of bone tissue is a carbonate-substituted apatite (CHA). The thermal stability of the CHA has been revealed to depend on the substitution type and degree, although relatively little is known about this behavior. The aim of this study was to investigate the carbonate loss from synthetic CHAs in equilibrium conditions in a wide temperature range. An approach based on FTIR spectroscopy of condensed gas phase was applied to evaluate the CO and CO2 release with increasing temperature. Four different CHAs were studied, which were prepared by either precipitation from solution or the solid-state interaction. The samples differ from each other by the substitution degree. In one of the samples calcium was partially substituted by magnesium. Decomposition was shown to start at surprisingly low temperature, about 400 degrees C, and the CO content increases monotonously with the increase of temperature. The CO2 content goes through a maximum due to its decomposition into carbon monoxide and oxygen, the temperature of this maximum being strongly dependent on the chemical synthesis route. Therefore, control of the sintering atmosphere with respect to the CO2/CO ratio is needed when preparing the carbonated apatite bioceramics., ((c) 2004 Wiley Periodicals, Inc.)

We developed a novel hydroxyapatite (HA) cylinder (HA-A) and compared the slow release of antibiotic in vitro as well as osteoconduction of the material in vivo to a commercially produced porous hydroxyapatite cylinder (HA-B). HA-A (4 x 4 mm) was synthesized by mixing HA powder, gelatin, and vegetable oil. The material had a bimodal pore size distribution, with intragranular (10 nm to 10 microm) and intergranular (100 microm) pores, and porosity of 40 vol %, while HA-B had pore sizes ranging from 50 to 300 microm and identical porosity. In vitro drug release was tested using antibiotics (isepamicin sulfate, vancomycin hydrochloride, and flomoxef sodium) soaked on the HA cylinders using a vacuum system. The mean adsorption efficiency was higher for HA-A (46%) than for HA-B (26%) and higher levels of antibiotic were released from HA-A. Of the antibiotics, ISP showed the longest release duration. Bone ingrowth into the pores was observed for both materials. Because the novel HA showed both the slower release of antibiotic (nanosize pores) and supported excellent osteoconduction (microsize pores), it could be useful for the treatment of osteomyelitis., (Copyright 2004 Wiley Periodicals, Inc.)

Development of a new calcium phosphate cement (CPC) system as an alternative to that commonly used, basically consisting of tetracalcium phosphate and dicalcium phosphate self-setting mixtures, could be of interest in achieving special properties of the product. Powder mixtures of Ca(OH)(2) and KH(2)PO(4) were studied to assess their potential for the precipitation of apatite-like phase with the use of potassium phosphate salt solution as the cement liquid. X-ray diffraction and infrared (IR) spectroscopy studies and pH and setting time measurements were performed. The set cement was revealed to consist of a low crystalline carbonate-substituted apatite-like phase. The setting time of the cement was about 5 min. Its dissolution in distilled water led to an increase in solution pH to about 11.5, the pH slowly decreasing to 10.2 at day 10. The results showed the cement to be of an increased carbonate substitution ability compared to the tetracalcium phosphate-dicalcium phosphate anhydrous cement., (Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 303-308, 2004)

Fluorinated hydroxyapatite is known to be less soluble by body fluids, resulting in enhanced resistance to biodegradation in vivo conditions, as compared to the pure hydroxyapatite ceramics. The present work was aimed at the investigation of the effect of minor additions of ultrafine fluorapatite (up to 10 wt%) on the sintering behavior and mechanical properties of hydroxyapatite ceramics. In vitro testing for the osteoblast-like cells viability and proliferation was performed with the samples of varying fluorapatite content. It was found that the fluorapatite addition hinders the sintering shrinkage and lowers the strength, but does not generally affect negatively the viability of the cells.

This study is aimed at the development of a method to fabricate porous spherical hydroxyapatite (HA) granules, which can be impregnated with a drug. These drug-loaded particles can be used as a system for targeted and time-controlled drug delivery, e.g. in bone surgery. The method to produce porous granules is based on liquids immiscibility effect. A suspension of HA powder in aqueous solution of gelatin and oil as a dispersion media were used. By stirring the mixtures of these immiscible liquids, granules of 50 2,000 microm diameter can easily be produced. Dependence of the granules characteristics on the preparation route was studied. In vivo experiments were performed to simulate drug release kinetics from the granules to the blood of rats.

A route for the fabrication of porous hydroxyapatite ceramics having two populations of open pores is reported. The bodies are prepared by sintering the spherical gelatin/hydroxyapatite granules. As the result, ceramics containing intragranular small-size pores and intergranular large-size interconnecting pores are obtained. The pore size and content are dependent on the route. Ceramics can generally be applied as bone replacement materials where the interconnections in the intergranular pores are the pathway to conduct cells and vessels for the bone ingrowth, whereas the intragranular pores can be filled with a drug, e.g. to eliminate infections.