Papers by Author: Sergey V. Dorozhkin

Abstract: Amorphous calcium phosphates (ACPs) represent a unique class of biomedically relevant calcium orthophosphate salts, in which there are neither translational nor orientational long-range orders of the atomic positions. Nevertheless, the constancy in their chemical composition over a relatively wide range of preparation conditions suggests the presence of a well-defined local structural unit, presumably, with the structure of Ca9(PO4)6 – so-called Posner’s cluster. ACPs have variable chemical but rather identical glass-like physicochemical properties. Furthermore, all ACPs are thermodynamically unstable compounds and, unless stored in dry conditions or doped by stabilizers, spontaneously they tend to transform to crystalline calcium orthophosphates. Although some order within general disorder is the most distinguishing feature of ACPs, the solution instability of ACPs and their easy transformation to crystalline phases might be of a great biological relevance. Namely, the initiating role ACPs play in matrix vesicle biomineralization raises the importance of this phase from a mere laboratory curiosity to that of a key intermediate in skeletal calcification. Furthermore, ACPs are very promising candidates to manufacture artificial bone grafts.

Abstract: Ceramics used for the repair and reconstruction of diseased or damaged parts of the musculo-skeletal system, termed bioceramics, can be bioinert, bioresorbable and bioactive, as well as porous for tissue ingrowth. This review is devoted to calcium orthophosphates, which belong to the categories of bioresorbable and bioactive bioceramics. There have been a number of major advances made in this field during the past 30 – 40 years. From initial work on development of bioceramics that were tolerated in the physiological environment, emphasis has now shifted towards the use of bioceramics that interact with bone tissue by forming a direct bond. By structural and compositional control, it is now possible to choose whether the bioceramics of calcium orthophosphates are biologically stable once incorporated within the skeletal structure or whether they are resorbed over time. Current biomedical applications of calcium orthophosphate bioceramics include replacements for hips, knees, teeth, tendons and ligaments, as well as repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jawbone, spinal fusion and bone fillers after tumor surgery.

Abstract: Mechanical properties of bioceramics are poor and need to be improved for biomedical applications. In order to do this, bioceramics may be strengthened by bioresorbable polymers. In this study, the mechanical properties of poly(ε-caprolactone), PCL, coated dense bioceramic pellets made of silica-contained calcium phosphates were studied and analyzed using a statistical experimental design in conjunction with Taguchi methods for optimization. The aim of this experimental work was to maximize the pellet flexural strength and minimize the amount of deposited PCL. The most important factors affecting the strengthening of the ceramic pellets were evaluated. Four independent processing variables (a removal technique of an excess polymer solution, concentration of PCL in the solution, a heat treatment temperature and the number of dipping) with three levels of variability were tested using an L9 (34) orthogonal array. A statistical experimental design using the analysis of means and orthogonal array was applied to optimize the responses of these variables. The optimal conditions for achieving the maximal flexural strength of the coated pellets at the minimal amount of the deposited PCL were determined. A high quality dense bioceramic pellets with ~ 10.5 MPa flexural strength and ~ 80 μm thickness (~ 21 mg weight) of the deposited PCL coating were manufactured as a result.

Abstract: There has been much recent activity in the research area of nanoparticles and nanocrystalline materials, in many fields of science and technology. This is due to their outstanding and unique physical, mechanical, chemical and biological characteristics. Recent developments in biomineralization have demonstrated that nano-sized particles play an important role in the formation of the hard tissues of animals. It is well established that the basic inorganic building blocks of bones and teeth of mammals are nano-sized and nanocrystalline calcium orthophosphates (in the form of apatites) of a biological origin. In mammals, tens to hundreds of nanocrystals of biological apatite are found to combine into self-assembled structures under the control of bio-organic matrixes. It was also confirmed experimentally that the structure of both dental enamel and bones could be mimicked by an oriented aggregation of nano-sized calcium orthophosphates, determined by the biomolecules. The application and prospective use of nano-sized and nanocrystalline calcium orthophosphates for clinical repair of damaged bones and teeth are also known. For example, a greater viability and a better proliferation of various cells were detected on smaller crystals of calcium orthophosphates. Furthermore, studies revealed that the differentiation of various cells was promoted by nano-sized calcium orthophosphates. Thus, the nano-sized and nanocrystalline forms of calcium orthophosphates have the potential to revolutionize the field of hard tissue engineering, in areas ranging from bone repair and augmentation to controlled drug delivery devices. This paper reviews the current state of knowledge and recent developments of various nano-sized and nanocrystalline calcium orthophosphates, covering topics from the synthesis and characterization to biomedical and clinical applications. This review also provides possible directions of future research and development.

Abstract: Composites of calcinated bovine bone derived hydroxyapatite (HA) with 5 and 10 wt % SrCO3 were prepared by sintering. The production of HA from natural sources is preferred due to money and time saving reasons. In this study scanning electron microscopy (SEM) investigations and together with measurements of microhardness, density, and compression strength were performed. The experimental results indicated that compression strength and microhardness values of HA-Sr-oxide composites decrease when the content of SrCO3 and sintering temperature increase. The best compression strength values were achieved after sintering at 1000°C. It was seen that at higher temperatures the compression strength and the microhardness values decrease due to the pore formation. The pore formation is very important for scaffold formation for tissue engineering purposes.

Abstract: Composites of calcinated bovine bone derived hydroxyapatite (HA) with 5, 7.5 and 10 wt % B2O3 were prepared by sintering. The production of HA from natural sources is preferred due to economical and time saving reasons. In this study scanning electron microscopy (SEM) investigations, microhardness and compression strength measurements were performed on composites. The experimental results indicated that compression strength and microhardness of HA-boron-oxide composites decrease when the content of boric acid and sintering temperature increase. The best mechanical properties achieved for 5 wt % addition of dehydrated boric acid. It was seen that at higher sintering temperatures, the compression strength and the microhardness decrease due to the very intensive pore formation. The results agree fairly well with microstructure analysis.

Abstract: Comparison of two experimental techniques of silicon-contained and/or silica-substituted calcium phosphate preparation from Ca(NO3)2·4H2O, NH4H2PO4, fumed silica and aqueous solution of NH4OH was performed. The first technique was a traditional one, in which the final product was synthesized in an aqueous solution by the well-known sol-gel process, followed by phase separation, washing off, drying and high-temperature sintering. An environmentally friendly direct preparation route was the second technique, in which the initial chemicals were mixed in the necessary proportions inside a crucible, followed by a high-temperature sintering of the entire mixture. The sintered powders were analyzed by the standard measurement techniques. Intentional variations from the stoichiometry within ±10% of the amounts of the mixed chemicals were employed to compare the vulnerability of both preparation techniques to random fluctuations of the processing parameters. The results revealed a better reproducibility and a higher yield of the direct preparation technique but the traditional sol-gel technique was found to be able to compensate accidental technological imperfections.

Abstract: Dense bioceramics made of pure hydroxyapatite (HA) was prepared and characterized. The cylindrical samples were compacted from HA powders of diverse pretreatments; namely, from spray-dried HA, calcined HA and mixtures thereof. The samples were prepared by a hydraulic press under different compaction loads both with and without auxiliary compounds (a binder and a lubricant). Both the total mass and geometrical dimensions of the prepared cylinders were measured. Then, the cylindrical samples were sintered at 1200 °C for 4 hours. After cooling down to ambient temperature, the sintered cylinders were weighed and their geometrical dimensions were measured once again. Mass decreasing and the shrinkage degree were calculated as a result. Afterwards, the compression strength of the sintered cylinders was measured by an Instron 5587 machine. Preparation of dense HA bioceramics possessing the highest possible compression strength was the purpose of this study. The necessary processing parameters were discovered.

Abstract: Revised simulated body fluid (rSBF) was prepared using a conventional route but all the chemicals were dissolved in commercial cow milk instead of de-ionized water. To accelerate crystallization and increase the amount of precipitates, the influence of milk on the crystallization of calcium phosphates was studied in supersaturated solutions equal to 4 times the ionic concentrations of rSBF. The experiments were carried out in physiological conditions, i.e. pH of 7.35–7.40, temperature of 37.0 (± 0.2) °C, and duration of 7 days, using a constant-composition double-diffusion (CCDD) device, which enables slow precipitation in strictly controlled crystallization conditions. Similar experiments with 4 times the ionic concentrations of rSBF using de-ionized water as solvent were carried out as control. For comparison purposes, another set of experiments with 4 times the ionic concentrations of rSBF in de-ionized water also containing 40 g of bovine serum albumin (BSA) per liter was also conducted. The experimental results showed that the behavior of milk was similar to the presence of dissolved BSA. Some components of milk, presumably proteins, co-precipitated with calcium phosphates. This phenomenon had a strong negative influence on the crystallinity of the precipitates.

Abstract: A simplified preparation method of silicon-substituted calcium phosphates with a very high yield (close to 100%) has been elaborated, according to the principles of Green Chemistry. The technique consists of mixing of crystals of calcium nitrate and ammonium dihydrogen phosphate in the desired proportions, following by addition of the necessary amount of a silicon-containing compound. The homogenous mixture is sintered between 900 and 1200°C. Either a siliconcontaining hydroxyapatite (Si-HA) or a silicon-stabilized tricalcium phosphate (Si-αTCP) can be synthesized, depending on the Ca/P, Ca/(P+Si) and Si/P molar ratios.