Interest in calcium phosphate cements as materials for the restoration and treatment of bone tissue defects is still high. Despite commercialization and use in the clinic, the calcium phosphate cements have great potential for development. Existing approaches to the production of calcium phosphate cements as drugs are analyzed. A description of the pathogenesis of the main diseases of bone tissue (trauma, osteomyelitis, osteoporosis and tumor) and effective common treatment strategies are presented in the review. An analysis of the modern understanding of the complex action of the cement matrix and the additives and drugs distributed in it in relation to the successful treatment of bone defects is given. The mechanisms of biological action of functional substances determine the effectiveness of use in certain clinical cases. An important direction of using calcium phosphate cements as a carrier of functional substances is the volumetric incorporation of anti-inflammatory, antitumor, antiresorptive and osteogenic functional substances. The main functionalization requirement for carrier materials is prolonged elution. Various release factors related to the matrix, functional substances and elution conditions are considered in the work. It is shown that cements are a complex system. Changing one of the many initial parameters in a wide range changes the final characteristics of the matrix and, accordingly, the kinetics. The main approaches to the effective functionalization of calcium phosphate cements are considered in the review.
The rate of resorption of calcium phosphate self-hardening materials for bone regeneration can be changed by changing the phase composition. The Ca3(PO4)2/CaCO3/Ca(H2PO4)2·H2O/Na2HPO4·12H2O system is important for the synthesis of self-curing bioactive materials with variable resorption rates by changing the ratios of the initial components. Cement compositions in twelve figurative points of a four-component composition diagram at a fixed content in the α-Ca3(PO4)2 system were studied with XRD, FTIR, SEM, calorimetric, and volumetric methods to obtain an idea of the effect of composition on solubility in vitro and resorption in vivo. It was found that the presence of the highly resorbable phase of dicalcium phosphate dihydrate in cement and the substitution of phosphate ions with the carbonate ions of hydroxyapatite increased solubility in vitro and resorption in vivo. The obtained results confirm the possibility of changing the solubility of a final product in the Ca3(PO4)2/CaCO3/Ca(H2PO4)2·H2O/Na2HPO4·12H2O system by changing the ratio of the initial components.
Low-temperature ceramics based on magnesium calcium phosphate cement are a promising resorbable material for bone tissue restoration with the possibility of functionalization. The replacement of the magnesium Mg2+ ion with a calcium Ca2+ ion at the stage of preparation of the precursor leads to the production of multiphase ceramics containing phases of brushite, monetite, and newberyite, with different dissolution rates. Multiphase ceramics leads to volumetric resorption with preservation of their geometric shape, which was confirmed by the results of an evaluation of the output of magnesium Mg2+ and calcium Ca2+ ions into the contact solution of the ceramics and the X-ray density of ceramic samples during subcutaneous implantation. The combined introduction of sodium pyrophosphate decahydrate and citric acid monohydrate as setting inhibitors neutralizes their insignificant negative effect on the physico-chemical properties of ceramics (strength, pH, porosity), determining the optimal composition. In vivo experiments with setting inhibitors in the composition of ceramics showed a different biological response, affecting the rate of resorption on par with magnesium ions. Preliminary data on biocompatibility and solubility determined magnesium-calcium phosphate ceramics containing additives that regulate setting to be a potential material for bone tissue restoration and a vector for further research, including in orthotopic implantation models.
Local drug delivery systems are an effective approach in the treatment of purulent–septic inflammation of bone tissue. Chemically bonded multiphase ceramics based on calcium-deficient carbonate-substituted hydroxyapatite combine resorbability, osteoconductivity, and the possibility of volumetric incorporation of antibiotics. Macroporosity is regulated by the concentration of polyethylene glycol granules introduced into the initial powder composition, followed by their extraction. The selected conditions for the consolidation of the ceramic matrix and the extraction of PEG granules retain the activity of vancomycin, which is confirmed by the results of microbiological studies. The concentration of vancomycin and the porosity affect the local concentration and release of the antibiotic. The incorporation method provides a prolonged release of the antibiotic for up to 31 days. In vivo experiments with bone implantation have shown that chemically bound macroporous ceramics with incorporated vancomycin are a therapeutically effective carrier of the substance during the healing of bone defects in conditions of surrounding purulent–septic inflammation, and can be considered as a carrier for local antibacterial therapy, at the site of implantation.
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