Antibacterial alginate/nano-hydroxyapatite composites for bone tissue engineering: Assessment of their bioactivity, biocompatibility, and antibacterial activity.

Bone substitute materials based on bioceramics and polymers have evolved shifting from a passive role where they are merely accepted by the body; to an active role, where they respond to particular environmental conditions or to different types of cues generating suitable integration (osseointegration for this case) inside the host tissue. In this work, two types of composite materials based on a bioceramic (synthetic nano-hydroxyapatite, HA) and a biopolymer (sodium alginate, ALG) have been designed and assessed for promoting the bone regeneration. These materials were loaded with ciprofloxacin (CIP) for obtaining, not only a suitable material for a filling but with antibacterial properties. Therefore, their main features were studied through Fourier transformed-infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and transmission electron microscopy (TEM). Ultraviolet-Visible (UV-Vis) spectroscopy was used for obtaining the released concentrations of CIP and Zeta-potential (ζ-potential) was used for characterizing the adsorption of CIP onto nanoparticles. The release profile of this drug has been fit with the Ritger-Peppas model, used for studying the release kinetics of hydrogel-based systems. The bioactivity of these composites was also evaluated after 30 days of incubation in a simulated body fluid solution (SBF). Then, the assessment of antibacterial capability against the three main strains cause osteomyelitis was performed. Finally, the cell viability study and the cellular morphology assay were also carried out. These last assays have shown encouraging results and, gathered with their other properties, such as their bioactivity and antibacterial properties; they could lead to propose these materials as new bone filler antibiotic devices.

Benedini L ，Laiuppa J ，Santillán G ，Baldini M ，Messina P ... -  《-》

Adsorption/desorption study of antibiotic and anti-inflammatory drugs onto bioactive hydroxyapatite nano-rods.

The use of high doses of antibacterial and anti-inflammatory drugs for patients with bone diseases, associated to implants or bone filling, can develop adverse effects; and consequently, it promotes to think new strategies to avoid this problem. In this work, it has been described the adsorption/release (or desorption) behavior of two drugs, ciprofloxacin (CIP) and ibuprofen (IBU), onto hydroxyapatite (nano-HA) at 37 °C. Through Ultraviolet-Visible (UV-Vis) spectroscopy, the concentrations of both drugs in adsorption, kinetic and desorption processes were obtained. The Fourier Transformed-Infrared (FT-IR) spectroscopy, Zeta-potential (ζ-potential), High-Resolution Transmission Electron Microscopy (H-TEM) and x-Ray Diffraction (xRD) were also used to characterize bared nanoparticles and those with adsorbed drugs. Five adsorption models (Langmuir, Freundlich, Sips, Temkin and Dubinin-Radushkevich) were used for describing the behavior of both active compounds. The adsorption processes (CIP/nano-HA and IBU/nano-HA) were better predicted by the Sips model than by the others. The kinetic adsorption data were processed, for both active agents, by application of Avrami's model. Desorption/release process (of both drugs) was evaluated though Korsmeyer-Peppas (K-P) model. Owing to the predictability of these systems, we propose the use of these active ceramics as potential bone filler for improving the treatment against bacterial bone infections and to avoid its associated inflammatory process.

Benedini L ，Placente D ，Ruso J ，Messina P ... -  《-》

Hydroxyapatite-ciprofloxacin delivery system: Synthesis, characterisation and antibacterial activity.

Ciocilteu MV ，Mocanu AG ，Mocanu A ，Ducu C ，Nicolaescu OE ，Manda VC ，Turcu-Stiolica A ，Nicolicescu C ，Melinte R ，Balasoiu M ，Croitoru O ，Neamtu J ... -  《-》

Synthesis, characterization, in vitro biocompatibility and antibacterial properties study of nanocomposite materials based on hydroxyapatite-biphasic ZnO micro- and nanoparticles embedded in Alginate matrix.

The paper presents the results of studies of biocompatibility and antibacterial properties of multiphase nanocomposite materials based on HA-Alg-ZnO (hydroxyapatite‑sodium alginate-biphasic zinc oxide) and HA-ZnO (hydroxyapatite‑zinc oxide), which were synthesized from the analytically pure calcium nitrate tetrahydrate, ammonium hydrophosphate, hydrous ammonia, zinc nitrate hexahydrate and calcium chloride. The samples' antimicrobial activity assessment was carried out on Gram-negative (E. coli, P. aeruginosa) and Gram-positive bacteria (S. aureus and S. epidermidis) test cultures by the co-incubation and modified "agar diffusion" methods. The murine fibroblast cells were used for the biocompatibility tests and cytotoxicity evaluation. It was shown that synthesized nanocomposite material has a multiphase nanoscale architecture, where ZnO nanocrystals are represented by two lattices: cubic and hexagonal. The possible explanation of ZnO nanocrystals' phase transition is given. At the same time, a partial replacement of Ca2+ ions by Zn2+ ions in the HA lattice possibly occurs due to processing of composite by US radiation. The replacement was evidenced by the non-stoichiometric Ca/P ratio < 2.16, OPO lines' shifting on FTIR spectrum and TEM analysis. The studied composite demonstrate a pronounced antibacterial activity due to the incorporation of ZnO particles into sodium alginate and moistened powder of hydroxyapatite. Both forms of HA-ZnO (suspension) and HA-Alg-ZnO (beads) are biocompatible. An interpretation of the process of Zn ions' embedding into hydroxyapatite and alginate matrix is given, as well as their influence on the biomimetic composite properties is discussed in details. STATEMENT OF SIGNIFICANCE: A number of studies have shown that Zn effectively inhibits the growth and development of bacteria and yeast fungi. Zinc plays an important role in the creation of new antimicrobial agents, and zinc-doped hydroxyapatite will find further application in biomedicine. In this regard, the phase states of zinc oxide, as well as the processes of calcium replacement by zinc in calcium apatite and in alginate should be explored fully. Nowadays we have lack of information and the study's results about those interactions. The present study provides data of the multiphase morphology, antimicrobial activity, biocompatibility and cytotoxicity of the biomimetic nanostructured composite materials, such as sodium alginate/hydroxyapatite/ZnO based granules and hydroxyapatite/ZnO based hydrogel, and the establishing Zn ions' behavior patterns with another composite components.

Turlybekuly A ，Pogrebnjak AD ，Sukhodub LF ，Sukhodub LB ，Kistaubayeva AS ，Savitskaya IS ，Shokatayeva DH ，Bondar OV ，Shaimardanov ZK ，Plotnikov SV ，Shaimardanova BH ，Digel I ... -  《-》

Formulation of biodegradable alginate-based nano-carriers for in-vitro drug delivery and antibacterial activity.

Sattar S ，Imran M ，Anwar A ，Akhtar MN ，Alsafari IA ，Khan FA ，Iqbal HMN ... -  《-》