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Based on carbonate-substituted hydroxyapatite (HAP) containing vancomycin, a method is developed for the preparation of macroporous matrices that combine bioresorbability, osteoconductivity, and the possibility for the volumetric impregnation of antibiotics without loss of their activity and their prolonged release. The technology includes treatment with supercritical CO2 as the final stage in the preparation of a matrix, which makes it possible to completely remove the organic solvent that serves as an extractant for the pore formation additive, i.e., polyethylene glycol (PEG) granules, and to increase the biocompatibility of the matrix, as confirmed by the results of histological tests during subcutaneous implantation. The activity of vancomycin after its volumetric incorporation into the calcium phosphate matrix is demonstrated in the regions of inhibiting the growth of bacterial cultures. As proven in in vivo experiments on the implantation of bones, the matrix is a therapeutically effective carrier of antibacterial substances in the treatment of septic purulent inflammations of bone tissues. [ABSTRACT FROM AUTHOR]

β-Tricalcium phosphate (β-Ca3(PO4)2) based ceramics with a relative density of 20–21%, grain size from 200 to 600 nm, and compressive strength from 1.6 to 1.8 MPa have been produced by 1000°C firing of cement stone prepared from a powder mixture having a Ca/P molar ratio of 1.5 and consisting of hydroxyapatite (Ca10(PO4)6(OH)2), calcium citrate tetrahydrate (Ca3(C6H5O7)2·4H2O), and calcium dihydrogen phosphate monohydrate (Ca(H2PO4)2·H2O). The mixing liquid used to initiate chemical binding reaction in the powder mixture was distilled water. The phase composition of the cement stone included brushite (CaHPO4·2H2O) and unreacted starting materials. The presence of platelike calcium pyrophosphate (Ca2P2O7) particles, formed from platelike brushite (CaHPO4·2H2O) particles, impeded densification of the ceramics during firing and ensured the formation of an ultraporous structure. The submicron-grained microstructure and phase composition of the β-Ca3(PO4)2-based ceramics resulted mainly from heterophase interactions between the products of thermal decomposition of cement stone components. Offering sufficient strength, biocompatible and bioresorbable ultraporous submicron-grained β-Ca3(PO4)2-based ceramics can be recommended for use in regenerative medicine for bone tissue defect repair. [ABSTRACT FROM AUTHOR]

A short-term intense cooling through the skin causes a response of the body. Potentially, it can be used to enhance bone healing. The aim of this study is to evaluate an effectiveness of a bone defect cryostimulation in the Wistar rat model in vivo. Through holes with a diameter of 2.15 mm were formed in the cortical layer of the diaphysis of the hind paws of rats. Further animals were subjected to cryotherapy 1 and 2 times a week (up to 6 weeks). The local average skin surface temperature dropped from 28 to 14 °C. The decrease in temperature in a control point inside the biological tissue was 5.3 °C. Micro CT and histological analyses showed that cryostimulation twice a week is efficient treatment. In this case, there was an acceleration of maturation of the newly formed bone tissue replacing the defect region. In the control, the newly formed immature bone with a large number of osteocytes and vessels was detected. In the experiment, the newly formed bone had a more mature structure with signs of a compact bone (formation of Haversian canals, reduction in the number of osteocytes, appearance of gluing lines). Morphometric analysis has showed a 2-fold decrease of the relative vessels area near the defect region and an increase of 30% in the content of mast cells in the entire bone marrow and especially near the site of osteogenesis. Generally, the complete filling of the critical size defect and almost complete mineralization have been observed. This information is expected to be useful for understanding the effect-exposure correlation of the cryotherapy and in the design of the cryotherapy protocols., (Copyright © 2023 Elsevier Ltd. All rights reserved.)