Bioactive and biocompatible copper containing glass-ceramics with remarkable antibacterial properties and high cell viability designed for future in vivo trials

Abstract

In the present study our interest is focused on finding the efficiency of 60SiO2·(32 - x)CaO·8P2O5·xCuO (mol%) glass-ceramics, with 0 ≤ x ≤ 4 mol%, in terms of bioactivity, biocompatibility, antibacterial properties and cell viability in order to determine the most appropriate composition for their further use in in vivo trials. The sol-gel synthesized samples show a preponderantly amorphous structure with a few crystallization centers associated with the formation of an apatite and calcium carbonate crystalline phases. The Fourier Transform Infrared (FT-IR) spectra revealed slightly modified absorption bands due to the addition of copper oxide, while the information derived from the measurements performed by transmission electron microscopy, UV-vis and electron paramagnetic resonance spectroscopy showed the presence of ions and metallic copper species. X-Ray photoelectron spectroscopic analysis indicated the presence of copper metallic species, in a reduced amount, only on the sample surface with the highest Cu content. Regarding in vitro assessment of bioactivity, the results obtained by X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy, demonstrated the formation of a calcium phosphate layer on all investigated sample surfaces. The inhibitory effect of the investigated samples was more significant on the Pseudomonas aeruginosa than the Staphylococcus aureus strain, the sample with the lowest concentration of copper oxide (0.5 mol%) being also the most efficient in both bacterial cultures. This sample also exhibits a very good bactericidal activity, for the other samples it was necessary to use a higher quantity to inhibit and kill the bacterial species. The secondary structure of adsorbed albumin presents few minor changes, indicating the biocompatibility of the glass-ceramics. The cell viability assay shows a good proliferation rate on samples with 0.5 and 1.5 mol% CuO, although all glass-ceramic samples exhibited a good in vivo tolerance.

First-Row Transition Metal Doping in Calcium Phosphate Bioceramics: A Detailed Crystallographic Study

“…The incorporation of inorganic antibacterial cations is a prerequisite for medical applications. In the last decade, silver (Ag + ), copper (Cu 2+ ), zinc (Zn 2+ ), and titanium (Ti 4+ ) have been investigated to prevent microbial infections while preserving non-toxicity toward human cells at low concentrations [19,20,21,22,23,24,25,26]. Manganese influences the regulation of bone remodeling, and a Mn-doped hydroxyapatite coating has shown a beneficial effect on bone cells, with a greater osteocalcin production, in a similar way to that of the well-known Sr 2+ doping effect [27].…”

New alginate-pullulan-bioactive glass composites with copper oxide for bone tissue regeneration trials

“…Sodium alginate powder was obtained from FMC BioPolymer, Norway, and pullulan polymeric powder was acquired from Hayashibara Biochemical Laboratories, Okayama, Japan (200 kDa). The bioactive glass‐ceramics with 60SiO 2 ·(32 − x)CaO·8P 2 O 5 ·xCuO (xCuBG) composition, with x = 0, 0.5, and 1.5 mol%, were synthesized by sol–gel route as previously described (Popescu et al, ), using tetraethylorthosilicate, triethylphosphate, calcium nitrate tetrahydrate (Ca(NO 3 ) 2 ⋅4H 2 O), and copper nitrate trihydrate (Cu(NO 3 ) 2 ·3H 2 O) hydrolysed in presence of nitric acid. Reactants were added consecutively after 1 hr, under continuous stirring.…”

“…Moreover, these properties can be further enhanced by the use of bioactive silicate glasses to create scaffolds and composites that promote regenerative healing (Boccaccini et al, ; Day et al, ; Hoppe & Boccaccini, ) on hard and soft tissue (Hench, , ; Popescu et al, ). Elements such as copper or silver increase tissue bonding properties of glass structures leading to improved angiogenic response and antibacterial effects and have been reported to promote bone growth and mineralization (Habibovic & Barralet, ).…”

“…In the previous study, we demonstrated that bioactive glass‐ceramics with 0.5 and 1.5 mol% CuO content have excellent cell viability and good antibacterial effect against Staphylococcus aureus (Popescu et al, ). Alginate and pullulan were widely used as a biomaterial for bone tissue engineering (Babu et al, ); thus, their use as composite components can be taken into consideration for tissue regeneration applications.…”

Comparison of the effects of 45S5 and 1393 bioactive glass microparticles on hMSC behavior

“…Since the earlier studies performed by Xynos et al numerous reports have highlighted the important role of ionic dissolution products of BAGs in the induction of genes relevant to cellular function, particularly those responsible for osteoblast metabolism, bone homeostasis, and angiogenesis . Thus, various types of BAGs have been developed with tailored chemical compositions and fine‐tuned ion release kinetics to harness distinct biological processes . This has opened a whole new exciting field of research of cell stimulation by synthetic materials without the need for organic growth factors .…”