Polina A. Krokhicheva

Injectable calcium–magnesium phosphate cements (CMPC) represent promising materials for bone defect reconstruction due to their bioresorbability, osteoconductivity, and potential to release biologically active Mg²⁺ ions. In this study, injectable CMPCs based on powders containing 20 and 60 mol.% Mg²⁺ were developed using a sodium phosphate solution containing carboxymethylcellulose (CMC) as the cement liquid. The effects of Mg²⁺ content and CMC incorporation on the physicochemical, handling, in vitro, and in vivo properties of the cements were systematically evaluated. CMC acted primarily as a rheology modifier and structuring agent, improving paste cohesion and injectability while maintaining compressive strength suitable for bone substitution. The developed cements demonstrated controlled degradation accompanied by sustained Mg²⁺ release and showed no cytotoxic effects toward MG-63 cells. Biological studies demonstrated favorable cellular responses and osteogenic potential of the developed materials. Importantly, the cement containing the higher Mg²⁺ concentration and CMC demonstrated the most favorable bone defect regeneration outcomes among the investigated formulations, as evidenced by the restoration of mineralized structures observed by micro-CT and the histological identification of newly formed bone tissue. These findings demonstrate that combining increased Mg²⁺ content with CMC-mediated control of cement handling properties is a promising strategy for developing injectable bioactive bone substitutes.

The development of multifunctional biomaterials for bone repair requires precursors that combine bioactivity, moderate antimicrobial growth-inhibitory effect, and imaging. This study demonstrates the multifunctional versatility of a single family of rare-earth-doped β-tricalcium phosphates (β-TCPs), Ca₉Eu(PO₄)₇ and Ca₉Dy(PO₄)₇, across three distinct formats: bioactive thin films (for implant coatings), brushite cements (for injectable bone fillers), and radiopaque PMMA bone composites (for load-bearing applications). This work serves as a proof-of-concept that the same doped phosphate precursors can address different clinical needs while retaining bioactivity, antimicrobial properties, and radiopacity. The phosphate precursors were synthesized via solid-state reaction. Pulsed laser deposition (PLD) was used to form amorphous, dense, and crack-free coatings, which exhibited excellent in vitro bioactivity through the rapid dissolution–reprecipitation of a carbonated apatite layer in simulated body fluid. The brushite-based bone cements were produced from doped β-TCPs. These cements demonstrated high cytocompatibility with mesenchymal stromal cells (>89% viability) and significantly enhanced osteogenic differentiation with antimicrobial activity against common pathogens (S. aureus, E. coli, P. aeruginosa). Furthermore, incorporation of these phosphates as fillers into PMMA bone cement resulted in a homogeneous particle distribution with reduced agglomeration compared to undoped β-TCPs, achieving clinically relevant radiopacity values (913 ± 22.4 HU for Dy-doped sample). Post-mortem studies by the CT method were performed on the vertebrae with PMMA–phosphate composites and brushite cements. It was shown that brushite cement in ovine lumbar vertebrae defects exhibited the highest radiopacity (1450–1550 ± 25 HU). The findings establish rare-earth-doped β-TCP as a unified multifunctional precursor that imparts bioactivity, the ability to support in vitro mineralization, antimicrobial properties, and enhanced radiopacity to thin films, phosphate cements, and polymer composite materials.

Due to their biocompatibility, biodegradability, injectability, and self-setting properties, calcium–magnesium phosphate cements (MCPCs) have proven to be effective biomaterials for bone defect filling. Two types of MCPC powders based on the magnesium whitlockite or stanfieldite phases with MgO with different magnesium contents (20 and 60%) were synthesised. The effects of magnesium ions (Mg²⁺) on functional properties such as setting time, temperature, mechanical strength, injectability, cohesion, and in vitro degradation kinetics, as well as cytocompatibility in the MG-63 cell line and the osteogenic differentiation of BM hMSCs in vitro, were analysed. The introduction of NaHA into the cement liquid results in an increase in injectability of up to 83%, provides a compressive strength of up to 22 MPa, and shows a reasonable setting time of about 20 min without an exothermic reaction. These cements had the ability to support MG-63 cell adhesion, proliferation, and spread and the osteogenic differentiation of BM hMSCs in vitro, stimulating ALPL, SP7, and RUNX2 gene expression and ALPL production. The combination of the studied physicochemical and biological properties of the developed cement compositions characterises them as bioactive, cytocompatible, and promising biomaterials for bone defect reconstruction.

Calcium sulfate (CS) materials containing terbium ions at 0, 1.0, or 2.0 mol.% were obtained by mechanochemical synthesis. According to X-ray diffraction data, the powder materials are characterized by the presence of a CaSO4×0.5H2O phase, while Tb3+ is incorporated into the lattice at ≤1.0 mol.%. Specific surface area enlarged from 2.1 to 22.5 m2/g as crystallite size decreased from 68 to 31 nm and the Tb3+ concentration increased up to 1.0 mol.%. Thermal analysis showed that terbium slightly raises the temperature of CaSO4×2H2O-to-CaSO4 transition. The presence of Tb3+ did not affect the solubility of the CS cements. Furthermore, after 7 days of soaking of the materials in a simulated body fluid, a calcium phosphate layer formed corresponding to a hydroxyapatite phase, in contrast to the pure cements. Luminescent properties were studied by excitation at 276 nm. The recorded emission peaks of the CS materials indicated that the luminescence of the samples is green and blue, with the most intense luminescence observed for samples containing 1.0 mol.% Tb3+. The developed materials can find applications in medicine as bioimplants for the regeneration and restoration of bone tissue with a possibility of noninvasive monitoring of the bone restoration process.

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 Zn²⁺ 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 Zn²⁺ 1.0 wt.%-substituted powders. Zn²⁺ 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.

The development of magnesium calcium phosphate bone cements (MCPCs) have garnered big 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 Zn2+ at 0.5 and 1.0 wt.% were obtained and investigated. After the mixing with a cement liquid, structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behaviour of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn2+ 1.0-wt.%-substituted powders. The Zn2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter up to 8 mm. Biological assays confirmed that the developed cements are cytocompatible and promising as a potential bone substitute in reconstructive surgery.

The paper is devoted to the creation and investigation of the new cement materials formed the new beryite phase (MgHPO₄·3H₂O) during the setting processes. A cement liquid based on sodium phosphate solution with addition of sodium hyaluronate polymer is used to increase the viscosity and the surface tension in the system and to increase the cohesion of the final product. The effect of cement liquids based on sodium hyaluronate with various concentrations are studied to estimate the phase composition, setting time, pH value, microstructure, injectivity, and strength properties of cement materials.

Powders based on β-tricalcium phosphate (β-TCP) containing sulphate groups at up to 12.0 mol.% were synthesised by chemical precipitation from aqueous solutions. The obtained materials were characterised by X-ray phase analysis, Fourier transform infrared spectroscopy, measurement of specific surface area, scanning electron microscopy, energy dispersive analysis, synchronous thermal analysis, mass spectra investigations and biological assays. It was established that during the synthesis, the obtained materials lose the sulphate groups in the course of heat treatment at 900 or 1200 °C. These groups stabilise low-temperature β-TCP, but when introduced at a high concentration, the sulphate groups contribute to the formation of hydroxyapatite during the heat treatment. Specific surface area of the powders proved to be in the range 81.7–96.5 m²/g. Results of biological assays showed cytocompatibility of both pure β-TCP and samples of sulphate-containing β-TCP. Additionally, matrix properties in the culture of MG-63 cells were revealed in all samples. Thus, the obtained materials are promising for biomedical applications.

In recent years, magnesium calcium phosphate materials have been considered as an alternative to calcium phosphate-based materials in reconstructive surgery. In this work, bone cements in the calcium phosphates–magnesium phosphates system were synthesized and studied. The interaction of this system with a cement liquid gives struvite MgNH₄PO₄·6H₂O as the main phase. The obtained materials have a compressive strength of up to 54 ± 5 MPa, a setting time of 6–7 min, and a neutral pH value. The effect of the introduction of vancomycin to the cement materials was studied. Investigation of the kinetics of vancomycin release showed that up to 98% of the antibiotic is released within 21 days. The materials exhibited pronounced antibacterial activity against the Staphylococcus aureus and Escherichia coli strains. After the introduction of vancomycin, the zone of inhibition of bacterial growth more than doubled compared to the reference samples. In vivo tests were conducted, the structural factors were calculated based on the results of micro-CT. According to macro and micro signs, the cement materials are fully biocompatible; by the sixth week, the formation of new bone tissue is observed.

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 (MgNH4PO4) -based cements, which grew in popularity in recent years, despite their neutral pH and acceptable mechanical performance, release undesirable NH4+ 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 Na2HPO4-based cement liquid. For this purpose, cement powders precursors in the CaO-MgO-P2O5 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.