Tricalcium phosphate cement supplemented with boron nitride nanotubes with enhanced biological properties

• Published in: Materials Science & Engineering C 2020-09, Vol.114, p.111044-111044, Article 111044
• Main Authors: Rau, Julietta V., Fosca, Marco, Fadeeva, Inna V., Kalay, Saban, Culha, Mustafa, Raucci, Maria Grazia, Fasolino, Ines, Ambrosio, Luigi, Antoniac, Iulian V., Uskoković, Vuk
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Biological properties; Biomedical materials; Bone cements; Bone Cements - pharmacology; Bone implants; Boron; Boron Compounds; Boron nitride; Boron nitride nanotubes; Calcium phosphate cement; Calcium Phosphates; Cell culture; Cell differentiation; Cell proliferation; Cement; Compressive strength; Crystallization; Crystals; Differentiation (biology); Human mesenchymal stem cells; Humans; Hydrogen Peroxide; Iron; Kinetics; Kinetics of hardening; Macrophages; Materials science; Mesenchyme; Nanotechnology; Nanotubes; Nucleation; Osteoblastogenesis; Osteoblasts; Phenotypes; Reactive oxygen species; Reactive oxygen species-associated damage; Reciprocity; Setting (hardening); Stem cells; Tricalcium phosphate
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.111044

A self-setting bone cement containing β-tricalcium phosphate (TCP) supplemented with boron nitride nanotubes (BNNTs, 1 wt%) was synthesized and analyzed in situ for its kinetics of hardening and selected physicochemical and biological properties. Moderately delayed due to the presence of BNNTs, the hardening reaction involved the transformation of the TCP precursor to the dicalcium phosphate (DCPD) product. In spite of the short-lived chemical transformations in the cement upon its hardening, the structural changes in it were extended. As a result, the compressive strength increased from day 1 to day 7 of the hardening reaction and the presence of BNNTs further increased it by ~25%. Fitting of the time-resolved energy-dispersive diffractometric data to the Johnson-Mehl-Avrami-Kolmogorov crystallization kinetics model conformed to the one-dimensional nucleation at a variable rate during the growth of elongated DCPD crystals from round TCP grains. For the first seven days of growth of human mesenchymal stem cells (hMSCs) on the cement, no difference in their proliferation was observed compared to the control. However, between the 7th and the 21st day, the cell proliferation decreased compared to the control because of the ongoing stem cell differentiation toward the osteoblast phenotype. This differentiation was accompanied by the higher expression of alkaline phosphatase, an early marker of hMSC differentiation into a pre-osteoblast phenotype. The TCP cement supplemented with BNNTs was able to thwart the production of reactive oxygen species (ROS) in hMSCs treated with H2O2/Fe2+ and bring the ROS levels down to the concentrations detected in the control cells, indicating the good capability of the material to protect the cells against the ROS-associated damage. Simultaneously, the cement increased the expression of mediators of inflammation in a co-culture of osteoblasts and macrophages, thus attesting to the direct reciprocity between the degrees of inflammation and stimulated new bone production. [Display omitted] •Selfsetting bone cement based on βtricalcium phosphate with boron nitride nanotubes•3D diffraction patterns and in situ analysis of crystallization kinetics•Compressive strength of the cement increased by 25%.•Cement protects human mesenchymal stem cells against reactive oxygen species damage.•Cement increases inflammation mediator expression and stimulates new bone growth.