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

Vladimir N Lebedev; Mariya I Kharovskaya; Bogdan I Lazoryak; Anastasiya O Solovieva; Inna V Fadeeva; Abdulkarim A Amirov; Maksim A Koliushenkov; Farid F Orudzhev; Oksana V Baryshnikova; Viktoriya G Yankova; Julietta V Rau; Dina V Deyneko

doi:10.3390/biomimetics9040252

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

Biomimetics (Basel). 2024 Apr 20;9(4):252. doi: 10.3390/biomimetics9040252.

Affiliations

¹ Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, Russia.
² Laboratory of Pharmacology Active Compounds, Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL-Branch of IC&G SB RAS), 630060 Novosibirsk, Russia.
³ A.A. Baikov Institute of Metallurgy and Material Science RAS, Leninskie, 49, 119334 Moscow, Russia.
⁴ Amirkhanov Institute of Physics, Dagestan Scientific Center of Russian Academy of Sciences, 367003 Makhachkala, Russia.
⁵ Physics Department, Lomonosov Moscow State University, Leninskie Gori 1, 119991 Moscow, Russia.
⁶ Geothermal and Renewal Energy Institute of the High Temperature Joint Institute of the Russian Academy of Sciences, 367015 Makhachkala, Russia.
⁷ Institute of Pharmacy, Department of Analytical, Physical and Colloid Chemistry, I.M. Sechenov First Moscow State Medical University, Trubetskaya 8, Building 2, 119048 Moscow, Russia.
⁸ Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, ISM-CNR, Via del Fosso del Cavaliere 100, 00133 Rome, Italy.
⁹ Laboratory of Arctic Mineralogy and Material Sciences, Kola Science Centre RAS, 14 Fersman Str., 184209 Apatity, Russia.

Abstract

β-tricalcium phosphate (β-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 β-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 Ca_9.5-xSr_xCu(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 β-TCP structure. No additional phases were formed up to x = 4.5 in Ca_9.5-xSr_xCu(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. Ca_9.5-xSr_xCu(PO₄)₇ powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca_9.5-xSr_xCu(PO₄)₇ were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca_9.5-xSr_xCu(PO₄)₇ renders them multifunctional materials suitable for bone substitutes.

Keywords: TCP; antibacterial; biomimetic properties; bone substitutes; calcium phosphate; whitlockite.

Grants and funding

23-73-10007/Russian Science Foundation