Strontium and Copper Co-Doped Multifunctional Calcium Phosphates: Biomimetic and Antibacterial Materials for Bone Implants.

ß-tricalcium phosphate (ß-TCP) is a promising material in regenerative traumatology for the creation of bone implants. Previously, it was established that doping the structure with certain cations can reduce the growth of bacterial activity. Recently, much attention has been paid to co-doped ß-TCP, that is explained by their ability, on the one hand, to reduce cytotoxicity for cells of the human organism, on the other hand, to achieve a successful antibacterial effect. Sr, Cu-co-doped solid solutions of the composition Ca9.5-xSrxCu(PO4)7 was obtained by the method of solid-phase reactions. The Rietveld method of structural refinement revealed the presence of Sr2+ ions in four crystal sites: M1, M2, M3, and M4. The M5 site is completely occupied by Cu2+. Isomorphic substitution of Ca2+ → (Sr2+and Cu2+) expands the concentration limits of the existence of the solid solution with the ß-TCP structure. No additional phases were formed up to x = 4.5 in Ca9.5-xSrxCu(PO4)7. Biocompatibility tests were performed on cell lines of human bone marrow mesenchymal stromal cells (hMSC), human fibroblasts (MRC-5) and osteoblasts (U-2OS). It was demonstrated that cytotoxicity exhibited a concentration dependence, along with an increase in osteogenesis and cell proliferation. Ca9.5-xSrxCu(PO4)7 powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca9.5-xSrxCu(PO4)7 were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca9.5-xSrxCu(PO4)7 renders them multifunctional materials suitable for bone substitutes.

Mn2+ Luminescence in Ca9Zn1-xMnxNa(PO4)7 Solid Solution, 0 ≤ x ≤ 1.

The solid solution Ca9Zn1-xMnxNa(PO4)7 (0 ≤ x ≤ 1.0) was obtained by solid-phase reactions under the control of a reducing atmosphere. It was demonstrated that Mn2+-doped phosphors can be obtained using activated carbon in a closed chamber, which is a simple and robust method. The crystal structure of Ca9Zn1-xMnxNa(PO4)7 corresponds to the non-centrosymmetric ß-Ca3(PO4)2 type (space group R3c), as confirmed by powder X-ray diffraction (PXRD) and optical second-harmonic generation methods. The luminescence spectra in visible area consist of a broad red emission peak centered at 650 nm under 406 nm of excitation. This band is attributed to the 4T1 → 6A1 electron transition of Mn2+ ions in the ß-Ca3(PO4)2-type host. The absence of transitions corresponding to Mn4+ ions confirms the success of the reduction synthesis. The intensity of the Mn2+ emission band in Ca9Zn1-xMnxNa(PO4)7 rising linearly with increasing of x at 0.05 ≤ x ≤ 0.5. However, a negative deviation of the luminescence intensity was observed at x = 0.7. This trend is associated with the beginning of a concentration quenching. At higher x values, the intensity of luminescence continues to increase but at a slower rate. PXRD analysis of the samples with x = 0.2 and x = 0.5 showed that Mn2+ and Zn2+ ions replace calcium in the M5 (octahedral) sites in the ß-Ca3(PO4)2 crystal structure. According to Rietveld refinement, Mn2+ and Zn2+ ions jointly occupy the M5 site, which remains the only one for all manganese atoms within the range of 0.05 ≤ x ≤ 0.5. The deviation of the mean interatomic distance (∆l) was calculated and the strongest bond length asymmetry, ∆l = 0.393 Å, corresponds to x = 1.0. The large average interatomic distances between Mn2+ ions in the neighboring M5 sites are responsible for the lack of concentration quenching of luminescence below x = 0.5.

Antimicrobial and Cell-Friendly Properties of Cobalt and Nickel-Doped Tricalcium Phosphate Ceramics.

ß-Tricalcium phosphate (ß-TCP) is widely used as bone implant material. It has been observed that doping the ß-TCP structure with certain cations can help in combating bacteria and pathogenic microorganisms. Previous literature investigations have focused on tricalcium phosphate structures with silver, copper, zinc, and iron cations. However, there are limited studies available on the biological properties of ß-TCP containing nickel and cobalt ions. In this work, Ca10.5-xNix(PO4)7 and Ca10.5-xCox(PO4)7 solid solutions with the ß-Ca3(PO4)2 structure were synthesized by a high-temperature solid-state reaction. Structural studies revealed the ß-TCP structure becomes saturated at 9.5 mol/% for Co2+ or Ni2+ ions. Beyond this saturation point, Ni2+ and Co2+ ions form impurity phases after complete occupying of the octahedral M5 site. The incorporation of these ions into the ß-TCP crystal structure delays the phase transition to the α-TCP phase and stabilizes the structure as the temperature increases. Biocompatibility tests conducted on adipose tissue-derived mesenchymal stem cells (aMSC) using the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay showed that all prepared samples did not exhibit cytotoxic effects. Furthermore, there was no inhibition of cell differentiation into the osteogenic lineage. Antibacterial properties were studied on the C. albicans fungus and on E. coli, E. faecalis, S. aureus, and P. aeruginosa bacteria strains. The Ni- and Co-doped ß-TCP series exhibited varying degrees of bacterial growth inhibition depending on the doping ion concentration and the specific bacteria strain or fungus. The combination of antibacterial activity and cell-friendly properties makes these phosphates promising candidates for anti-infection bone substitute materials.