Soluble phosphate salts as setting aids for premixed calcium phosphate bone cement pastes

Recently, premixed calcium phosphate cement pastes have been proposed as biomaterials for bone tissue repair and regeneration. Use of premixed pastes saves the time and removes an extra step during a medical operation. α-Tricalcium phosphate (α-TCP) based cements set to form calcium deficient hydroxyapatite which has a moderate bioresorbtion speed. α-TCP cements require a setting aid, usually a sodium or potassium phosphate salt, to speed up the setting process. Within the current research we investigated which setting aid has significant advantage, if α-TCP is used in form of non-aqueous premixed paste. This approach offers the application of simple ingredients to produce a premixed calcium phosphate cement. The following properties of cement formulations were evaluated: cohesion, phase composition, microstructure, pH value of the liquid surrounding the cement, and compressive strength.Compositions using mixture of basic and acidic potassium phosphate salts (KH₂PO₄ and K₂HPO₄) in sufficient amounts give the best overall results (adequate cohesion and pH of the surrounding liquid, hydrolysis of starting materials within 48 h, and compressive strength of 12 ± 3 MPa). Cement prepared with basic sodium phosphate salt (Na₂HPO₄) as setting aid had considerably higher compressive strength 22 ± 1 MPa, but the pH of the surrounding liquid was basic (9.0).     

Synthesis and characterization of lithium calcium phosphate ceramics

The crystal structure, thermal, dielectrical, alternating current conductivity and microstructure properties of lithium calcium phosphate ceramics synthesized by the sol–gel method were investigated. The average crystallite size, crystallinity, activation energy and enthalpy of crystallization of Ca₁₀Li(PO₄)₇ ceramics were determined. The X-ray diffraction (XRD) results indicated that the apatitic structure belonging to HAp was transformed fully to Ca₁₀Li(PO₄)₇ phase with the addition of Li. The Avrami exponents of the samples suggest that the crystallization mechanism is based on the surface nucleation and one-dimensional growth. It was found that the alternating current conductivity mechanism of the ceramics is controlled by the hopping motion involving a translational motion with a sudden hopping. The dielectric constant of the samples shows a small increase with increasing amount of Li.     

Evaluation of biphasic calcium phosphate/nanosized 3YSZ composites as toughened materials for bone substitution

In this research, biphasic calcium phosphate (BCP), comprising 70 wt% of beta tricalcium phosphate and 30 wt% of hydroxyapatite, was mixed with different amounts of 3 mol% yttria-stabilized zirconia (3YSZ) and sintered at 1200 °C to produce toughened bone substitutes. The fracture toughness (K_Ic) of the obtained bodies was determined using the indentation-strength fracture method. Scanning electron microscopy and energy dispersive X-ray spectroscopy analysis were utilized to study the microstructure of the samples. The phase composition of the samples was also determined using X-ray diffraction technique. In order to investigate the cell supporting ability of the samples, G-292 cells were cultured on them and cell morphology was evaluated after 48 h. Based on the results, the maximum fracture toughness and compressive strength values (i.e., 2.11 MPa m^0.5 and 150 MPa, respectively) were obtained for the sample containing 3 vol% of 3YSZ. The obtained fracture toughness value was approximately two times higher than that of the original BCP (1.07 MPa m^0.5) and also was comparable with that of the cortical human bone. The following mechanisms for the improved K_Ic of the β-tricalcium phosphate were determined: Grain bridging of 3YSZ particles during crack growth resistance, formation of microcracks on the tip of the larger cracks, absorbing crack extension energy due to the volume expansion during 3YSZ tetragonal-monoclinic transformation and crack deflection by the presence of 3YSZ particles. Also, 3YSZ additive encourages transformation of HA phase into β-TCP during sintering BCP. Finally, based on the cell studies, the samples exhibited an adequate cell attachment and a good cell spreading condition.     

Bioceramic composites for orthopaedic applications: A comprehensive review of mechanical,biological, and microstructural properties

Bioceramics have been widely utilized for orthopaedic applications in which the biocompatibility and mechanical properties of the materials are vital characteristics to be considered for their clinical use. Till date, extensive studies have been devoted to developing a range of scientific ways for tailoring the microstructure of bioceramics in order to attain the trade-off of mechanical properties and biocompatibility of the final product. Owing to low reactivity, earlier stabilization and longer functional life of bioceramic, the developed implants are capable of replicating the mechanical behaviour of original bone. As the safety of the patient and its ultimate functionality are the ultimate goal of the selected implant material hence, the present literature survey investigates and brings forth the important aspects associated to the mechanical, biological and microstructural characteristics of bioceramics employed in orthopaedic applications. The review paper majorly focuses on effective utilization of various materials as an additive in bioceramics and processing techniques used for enhancement of properties, enabling the use of material in orthopaedic applications. The influence of various additives on the microstructure, mechanical properties and biological performance of developed bioceramics orthopaedic implants has been elaborately discussed. Furthermore, future prospects are proposed to promote further innovations in bioceramics research.     

In vitro characterization of porous calcium phosphate scaffolds capped with crosslinked hydrogels to avoid inherent brittleness

Ductile composite scaffolds can avoid being crushed during filling processes in clinical applications. Thus, this study aimed to modify brittle porous ceramic scaffolds into ductile scaffolds through hydrogel capping. The surfaces of calcium phosphate (CaP) ceramic scaffolds were effectively capped with alginate/gelatin hydrogels. The composite scaffolds were then crosslinked, subjected to vacuum drainage, and washed prior to lyophilization. The detailed controlled approach in this study was proposed with the aim to develop biocompatible composites with anisotropic open pores through the formation of a thin, homogenous, hydrogel film coating on porous ceramic scaffold surfaces. The performances of the hydrogel/CaP composite scaffolds were evaluated on the basis of their morphological characteristics, compressive strengths, and cell viabilities. Results showed that strength, toughness, and specimen integrity after cracking are strongly related to the concentration of the hydrogel cap. Strength testing results showed that the use of 50 vol% alcohol as the crosslinker removal solution yielded scaffolds with high toughness and ductility. Moreover, the cracked specimen dipped in 50 vol% alcohol possessed better integrity than that dipped in water only. This study successfully identified the optimal hydrogel quantity for the fabrication of biocompatible scaffolds with open connective pores. The advantages of the fabricated scaffolds indicate the relevance of the proposed method to clinical applications, such the production of fillers for successful alveolar bone augmentation.     

Crystallization behavior and density functional theory study of solution combustion synthesized silicon doped calcium phosphates

The influence of heat-treatment temperatures (700 °C, 900°C, 1200 °C) on the phase, physical properties, crystallization rate, and in vitro properties of the solution combustion synthesized silicon-doped calcium phosphates (CaPs) were investigated. The thermodynamic aspects (enthalpy, entropy, and free energy) of the synthesis process and the crystallographic properties of the final samples were first predicted and then confirmed using density functional theory (DFT). Results demonstrated that the crystallization rate was controlled by the fuel(s) type (glycine, citric acid, and urea) and the amounts of Si⁴⁺ ions (0, 0.1, 0.4 mol). The highest calculated crystallization rate values of the un-doped, 0.1, and 0.4 mol Si-doped samples were 64%, 22%, 38%, respectively. The obtained results from the DFT simulation revealed that crystal growth in the direction of c-axis of hydroxyapatite (HAp) structure could change the stability of (001) surface of (HAp). Also, the computational data confirmed the adsorption of Si–OH groups on the (001) surface of HAp during the SCS process with an adsorption energy of 1.53 eV. AFM results in line with DFT simulation showed that the observed change in the surface roughness of Si-doped CaPs from 2 to 8 nm could be related to the doping of Si⁴⁺ ions onto the surface of CaPs. Besides, the theoretical and experimental investigation showed that crystal growth and doping of Si⁴⁺ ions could decrease the activation energy of oxygen reduction reaction (ORR). Furthermore, the results showed that the crystallized HAp structure could have great potential to efficiently reduce oxidative stress in human body.     

Investigation of calcium phosphate formation from calcium propionate and triethyl phosphate

Synthetic calcium phosphates are used in for example bone cements and implant coatings to increase biocompatibility. The common method to produce tricalcium phosphate (TCP) uses high temperatures, which creates large crystals with low specific surface areas. In order to investigate new methods to produce TCP at lower temperatures, the reaction between calcium propionate and triethyl phosphate conducted at 220 °C was studied. The method had a near 100% conversion rate, the main synthesis products were calcium phosphate and ethyl propionate. The formed calcium phosphate polymorph could be controlled depending on the water content of the precursor mixture. Anhydrous conditions created amorphous calcium phosphate. As the concentration of water increased, β-TCP was formed, followed by calcium deficient hydroxyapatite and monetite. The particle size increased with the water content, from 20 to 40 nm for amorphous calcium phosphate to tenths of micrometers for monetite. The specific surface areas varied between 209 m²/g for the amorphous product to 3.6 m²/g for the monetite product.     

Synthesis and characterization of microporous titanosilicate ETS-10 with different titanium precursors

This work was aimed to identify the influence of different titanium sources, namely nano-sized Degussa TiO₂ (commercially known as P25), TiCl₃, TiF₄, and (NH₄)₂F₆Ti, on the crystallization of micropoprous titanosilicate ETS-10. The characterization results of XRD, FESEM, Raman, and FTIR showed that the morphology, particle size, and purity of the final products were strongly dependant on the titanium sources because of the different crystallization mechanisms of ETS-10 in the presence of different titanium precursors. The different coordination states of Ti atoms and anions of the titanium precursors were observed to play a role in the formation of ETS-10.     

In-vitro behavior of different fully dense calcium phosphate materials fabricated by Spark Plasma Sintering

Results obtained during in-vitro experiments concerning human osteoblasts cultivated on the surface of dense samples produced by Spark Plasma Sintering from three types of hydroxyapatite powders are described and discussed. The sintered products display diverse composition and microstructures which are found to significantly influence the biological response of the cells. Osteoblasts adhesion, viability and proliferation are quantitatively comparable for the three classes of bioceramics, whereas matrix mineralization occurs only in products exclusively consisting of hydroxyapatite. Correspondingly, a calcium-phosphate layer exhibiting a trabecular-like microstructure is deposited on the materials surface. Matrix mineralization is favored when the substrate is composed of submicrometer-sized apatite grains. On the other hand, the latter phenomena is markedly suppressed, and so does the formation of the new apatite phase, when cells are seeded on sintered disks composed of β-Tri-Calcium Phosphate, which was formed during the sintering process from the decomposition of initial apatite.     

Multiphasic calcium orthophosphate (CaPO4) bioceramics and their biomedical applications

Due to the chemical similarity to the inorganic constituents of calcified tissues of mammals, biologically relevant calcium orthophosphates (CaPO₄) have been applied as artificial bioceramics suitable for reconstruction of various types of bone defects. Since none of the known individual types of CaPO₄ appears to be able to mimic both the composition and the properties of natural bones, various attempts have been sought to overcome this problem and a multiphasic (polyphasic) concept is one of the reasonable solutions. In general, this approach is determined by advantageous formulations consisting of homogeneous blends of two (biphasic), three (triphasic) or more (multiphasic) individual CaPO₄ phases possessing diverse solubility and, therefore, bioresorbability, while the optimum ratios among the phases depend on the definite applications. Therefore, all currently known multiphasic CaPO₄ formulations are sparingly soluble in water and, thus, after being implanted they are gradually resorbed inside the body, releasing calcium and orthophosphate ions into the biological medium and, hence, seeding a new bone formation. They have already demonstrated a proven biocompatibility, osteoconductivity, safety and predictability in vitro, in vivo, as well as in clinical trials. More recently, in vitro and in vivo studies have shown that some of them might possess osteoinductive properties. Hence, in tissue engineering, multiphasic CaPO₄ bioceramics represent promising formulations to construct various scaffolds capable of carrying and/or modulating the behavior of cells. This review summarizes the available information on biphasic, triphasic and multiphasic CaPO₄ bioceramics including their biomedical applications. New formulations have been proposed as well.     

Phase equilibria in CaNaPO4-CaKPO4 system and their influence on formation of bioceramics based on mixed Ca-K-Na phosphates

An investigation of the two-component phase diagram of the CaNaPO₄- CaKPO₄system performed using various analysis techniques is reported. The continuous solid solution series of α-CaMPO₄ existing above 700 °C undergoes eutectoid decomposition during cooling to β-CaMPO₄-based solid solutions enriched with Na and K, and to an intermediate nonstoichiometric compound with an ideal composition of CaK_0.6Na_0.4PO₄. All three compounds exhibit significant volumetric effects associated with first-order phase transitions, with positive volume changes under cooling for the intermediate compound. Increased K content in ceramics based on CaK_yNa_1-yPO₄ compositions enhances the strength properties of those ceramics, including their fracture toughness, which is associated with increased density. Increased K content also has a smaller effect of inducing phase transformations accompanied by strong volume changes.     

Green synthesis of calcium silicate bioceramic powders

Calcium silicates have proven to be potential candidates for biomedical applications because of their osteogenic properties. Sol–gel methods are typically used for the preparation of calcium silicate powders. However, in the sol–gel route, an acid or base and ethanol are used to catalyze the precursors. From the perspective of green chemistry, it is better to avoid the use of organic solvents. The objective of this study was to prepare calcium silicate powders using a green synthesis route (hydrothermal method) without organic solvents. The powders were also prepared via the sol–gel process using tetraethoxysilane (TEOS) and calcium nitrate as the raw materials for the purpose of comparison. The powders were sintered at temperatures ranging from 600 to 1000 °C after the application of both methods. To understand the feasibility of using the resulting materials in medical applications for bone repair, the powders were mixed with water to form cements. The results indicated that the powder composition was not significantly affected by the different techniques but was dependent on the Ca:Si ratio of the precursors and on the sintering temperature. The different techniques produced no differences in powder morphology. In addition, the setting times of the powder-derived cements were found to be independent of the sintering temperature and synthesis technique, but it was affected by the Ca:Si ratio of the precursors. The mechanical strength of the cements was similar. These encouraging results suggest that the hydrothermal method is a potentially beneficial alternative to the sol–gel route for the production of calcium silicate powders.     

Comparison of DOPA and DPPA liposome templates for the synthesis of calcium phosphate nanoshells

The aim of this paper is to synthesise calcium phosphate (CaP) nanoshells by controlling their particle size and shape using negatively charged liposomes (1,2 dioleoyl-sn-glycero-3 phosphate sodium salt (DOPA) and 1,2-dipalmitoyl-sn-glycero-3-phosphate sodium salt (DPPA)) as a template. The morphology, particle size, size distribution and zeta potential properties of DOPA and DPPA liposome templates were determined. The results showed that both DOPA and DPPA formed spherical nanoshell structures to be used as templates for the synthesis of CaP nanoshells. By using the DOPA template, spherical CaPs structures with a mean particle size of 197.5 ± 5.8 nm were successfully formed. In contrast, needle or irregularly shaped CaP particles were observed when using the DPPA template.     

In vitro behaviour of Nurse's Ass-phase: A new calcium silicophosphate ceramic

In the present study, a new single phase Si–Ca–P-based ceramic (called Nurse's A_ss) was obtained and its in vitro behaviour was explored for potential bone tissue regeneration. A porous Si–Ca–P single phase ceramic was obtained from high-temperature sintering of previously synthesised γ-dicalcium silicate and β-tricalcium phosphate. Apatite-mineralisation ability and the dissolution rate were systematically studied by immersing the material in simulated body fluid (SBF) for several time points. Massive new dense calcium deficient hydroxyapatite (CDHA) layer formation was observed at the SBF-sample interface. Adjacent to the dense CDHA layer, a porous structure developed parallel to the interface, formed by the pseudomorphic transformation of Si–Ca–P (Nurse's A_ss) into CDHA. The cell attachment test showed that the new material supported adult human bone marrow-derived mesenchymal stem cells (hMSCs) adhesion and spreading, and cells came into close contact with the ceramic surface during an extended 28-day culture. These findings indicate that the new calcium silicophosphate ceramic possesses good bioactivity and biocompatibility, and might be a promising bone graft substitute.     

Synthesis and characterization of calcium zirconate nanofibers produced by electrospinning

Calcium zirconate fibers were produced by electrospinning and characterized in this work. The solution was prepared from zirconium and calcium salts, using polyvinyl-pyrrolidone (PVP) as processing aid. The decomposition of the organic fraction and crystallization of calcium zirconate were followed by thermogravimetry and differential scanning calorimetry (TG/DSC). Raman Spectroscopy was used to measure the vibrational modes in the green as well as in the calcined fibers. The final phase composition was studied by means of X-ray diffraction (XRD). The fiber morphology was investigated by confocal laser scanning microscopy (CLS) and scanning electron microscopy (SEM). The formation reaction of calcium zirconate was observed at about 740 °C. Highly crystalline fibers were obtained already at 800 °C, but the crystallinity and calcium zirconate yield improved when the temperature was increased to 1000 °C.     

Fabrication of biphasic calcium phosphates nanowhiskers by reflux approach

Nanowhiskers of biphasic calcium phosphates composed of monetite/hydroxyapatite were fabricated using a cost-effective reflux hydrothermal approach from calcium nitrate and ammonium hydrogen phosphate precursors in presence of urea. The produced nanowhiskers were characterized using, FT-IR-spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron micrograph (TEM) and BET surface area determination. The major phase in Biphasic was (monetite, CaHPO₄.) and their grown crystals were morphologically formed with irregular sizes of well defined rod or whiskers crystal structure. The specific surface area of these fabricated nanowhiskers was found to be 8.48?m²/g according to BET studies. The N₂ adsorption/desorption isotherm of the as prepared monetite calcium phosphate is of type IV indicating that this material has a mesoporous structure. The produced nanowhiskers had 80% of monetite and 20% is hydroxyapatite. By controlling the parameters of the reflux approach it is possible to manipulate the composition and the size of these produced nanowhiskers.     

Synthesis of silicon-substituted hydroxyapatite by a hydrothermal method with two different phosphorous sources

Silicon-substituted hydroxyapatite (Si-HA) with up to 1.8 wt% Si content was prepared successfully by a hydrothermal method, using Ca(NO₃)₂, (NH₄)₃PO₄ or (NH₄)₂HPO₄ and Si(OCH₂CH₃)₄ (TEOS) as starting materials. Silicon has been incorporated in hydroxyapatite (HA) lattice by partially replacing phosphate (PO₄³⁻) groups with silicate (SiO₄⁴⁻) groups resulting in Si-HA described as Ca₁₀(PO₄)_6−x(SiO₄)_x(OH)_2−x. X-ray diffraction (XRD), Fourier transform IR spectroscopy (FTIR), inductively coupled plasma AES (ICP-AES) and scanning electron microscopy (SEM) techniques reveal that the substitution of phosphate groups by silicate groups causes some OH⁻ loss to maintain the charge balance and changes the lattice parameters of HA. The crystal shape of Si-HA has not altered compared to silicon-free reference hydroxyapatite but Si-incorporation reduces the size of Si-HA crystallites. Based on in vitro tests, soaking the specimens in simulated body fluid (SBF), and MTT assays by human osteoblast-like cells, Si-substituted hydroxyapatite is more bioactive than pure hydroxyapatite.     

Synthesis and characterization of cast resin based on different saturation epoxidized soybean oil

Acrylated epoxidized soybean oils (AESOs) with different level of saturation were obtained by the ring opening of different saturation epoxidized soybean oils using acrylic acid as the ring opener. AESO‐based thermosets have been synthesized by free radical polymerization of these AESOs and methyl methacrylate. The thermal properties of these resins were studied by differential scanning calorimetry and thermo‐gravimetric analysis. The results indicated that the thermal stability of these resins depends upon the epoxy value; the glass transition temperature increases with increasing of epoxy value. The tensile and impact strength of the resins were also studied, and indicated that tensile strength increases with increasing epoxy value, whereas impact strength decreases. The resulting thermosets ranged from elastomers to glassy polymers.     

Synthesis of functional gradient BCP/ZrO2 bone substitutes using ZrO2 and BCP nanopowders

BCP/BCP-ZrO₂/ZrO₂ scaffold with a functionally gradient layered structure (FG BCP/ZrO₂) was fabricated by the polymeric sponge replica method and subsequent dipping process. To enhance the compressive strength and bioactive properties of monolithic ZrO₂ scaffold, ZrO₂ and BCP phases were selected as a main frame and surface layer, respectively. The formation of microcracks was significantly decreased by incorporating an intermediate layer consisting of BCP-ZrO₂ phase. The thicknesses of the monolithic ZrO₂, BCP-ZrO₂, and BCP layer were around 10-30 μm, 3-5 μm, and 2-3 μm, respectively. The FG BCP/ZrO₂ scaffold showed highly interconnected pores as well as good material properties, which were 68% porosity and 7.2 MPa of compressive strength. Average pore size of FG BCP/ZrO₂ scaffold was about 220 μm in diameter. From MTT assay and SEM observation of osteoblast-like MG-63 cells, FG BCP/ZrO₂ scaffold showed good cell viability and faster proliferation behavior.     

Synthesis of nanosized powders and coatings of calcium phosphates

Hydroxyapatite powders with a particle size of nearly 100 nm, i.e., rather close to bone crystals shaped as 60 × 20 × 5-nm flattened prisms, were synthesized by the pyrolysis of a solution of calcium oleate in tributylphosphate. The possibility of synthesizing hydroxyapatite coatings on different ceramic materials was demonstrated. The pyrolysis of a solution of strontium oleate in tributylphosphate was established to produce the Sr10(PO₄)₆(OH)₂ compound isotypical to hydroxyapatite, which in turn creates prospects for synthesizing materials based on hydroxyapatite with some calcium atoms substituted by strontium.