Development and characterisation of novel Ce‐doped hydroxyapatite–Fe ₃ O ₄ nanocomposites and their in vitro biological evaluations for biomedical applications

Abstract

Hydroxyapatite (HAP: Ca 10 (PO 4) 6 (OH) 2) is extensively used in biomedical field because of its biocompatibility, osteoconductivity and non-toxicity properties. However, HAP exhibits poor mechanical strength and bacterial restriction behavior. To overcome these drawbacks, various metal ions such as Ag + , Zn 2+ , Cu 2+ , Ti 4+ and Ce 4+/3+ are incorporated in HAP matrix to increase the mechanical and biological properties. Among these, Cerium (Ce) is selected as antibacterial agent due to its high thermal stability and its applications in dental fillings, bone healing and catheters. Fe 3 O 4 nanoparticles were used in hyperthermia treatment, magnetic fluid recordings and catalysis. In this present study, we have synthesized nanocomposites consisting of 1.25% Ce doped HAP with various concentrations of Fe 3 O 4 NPs as 90:10 (C-1), 70:30 (C-2) and 50:50 wt% (C-3) using ball milling technique. The obtained Ce@HAP-Fe 3 O 4 nanocomposites were characterized by ATR-FTIR, XRD, VSM, SEM-EDAX and TEM analysis. Further, the fabricated Ce@HAP-Fe 3 O 4 nanocomposites were tested for its antibacterial activity towards Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli), where C-3 composites exhibit the excellent pathogen inhibition towards E.coli. In addition, the cytotoxicity evaluation on C-3 nanocomposites by in vitro biocompatibility study using MG-63 cells shows the prominent viable cell enhancement up to 400µg/mL concentrations.

Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods

“…Cerium (Ce) cation is characterized by an ionic radius and electronegativity similar to Ca 2+ . Ce can easily substitute calcium, accumulate in small quantities in bones, and boost the bone metabolism and the biomimetic HA-forming ability [1,344,381]. Moreover, Ce participates in the prevention of dental cavities, reduction of enamel demineralisation, acts as an antioxidant, and provides high thermal-phase stability [344,381,382].…”

“…Ce can easily substitute calcium, accumulate in small quantities in bones, and boost the bone metabolism and the biomimetic HA-forming ability [1,344,381]. Moreover, Ce participates in the prevention of dental cavities, reduction of enamel demineralisation, acts as an antioxidant, and provides high thermal-phase stability [344,381,382]. In vitro biomimetic apatite formation, after being soaking in SBF for periods of 2–3 weeks has been noticed for Ce-HA materials [383,384].…”

“…In vitro biomimetic apatite formation, after being soaking in SBF for periods of 2–3 weeks has been noticed for Ce-HA materials [383,384]. Ce can also stimulate the antimicrobial activity, pathogen inhibition and regenerative properties [344,377,381,382]. Both Ce 4+ and Ce 3+ cations are present in Ce-substituted HAs, but in proportions dependent on experimental procedure [348,349,385].…”

“…Both Ce 4+ and Ce 3+ cations are present in Ce-substituted HAs, but in proportions dependent on experimental procedure [348,349,385]. Various studies have reported the antibacterial properties of Ce-doped HA for Gram-positive (e.g., S. aureus [344,348,377,381,382,385], Lactobacillus [377], and B. subtilis [348]) and Gram-negative (e.g., E. coli [348,377,381,382,385]) strains. However, discrepancies exist in the reported Ce content able to induce an antibacterial effect.…”

“…The antibacterial activity for such high Ce doping levels was also confirmed by Sundarabharathi et al [344] against P. aeruginosa and S. aureus , for sol-gel prepared Ce-doped (10 at.%) HA, and G. Ciobanu et al [385], against E. coli and S. aureus , for co-precipitation synthesized Ce-doped (10, 20 and 25 at.%) HA. However, some studies report antibacterial activity below 8 at.% Ce doping levels, specifically in the range for 0.3–1.25 at.%, for both co-precipitation [382] and sol-gel [348,381] Ce-doped HAs. Since Gram-negative bacteria have a less complex and thinner cell wall, it is expected that they are more sensitive to antibiotics than Gram-positive bacteria [348].…”