Highly porous phosphate-based glasses for controlled delivery of antibacterial Cu ions prepared via sol-gel chemistry.

Mesoporous glasses are a promising class of bioresorbable biomaterials characterized by high surface area and extended porosity in the range of 2 to 50 nm. These peculiar properties make them ideal materials for the controlled release of therapeutic ions and molecules. Whilst mesoporous silicate-based glasses (MSG) have been widely investigated, much less work has been done on mesoporous phosphate-based glasses (MPG). In the present study, MPG in the P2O5-CaO-Na2O system, undoped and doped with 1, 3, and 5 mol% of Cu ions were synthesized via a combination of the sol-gel method and supramolecular templating. The non-ionic triblock copolymer Pluronic P123 was used as a templating agent. The porous structure was studied via a combination of Scanning Electron Microscopy (SEM), Small-Angle X-ray Scattering (SAXS), and N2 adsorption-desorption analysis at 77 K. The structure of the phosphate network was investigated via solid state 31P Magic Angle Spinning Nuclear Magnetic Resonance (31P MAS-NMR) and Fourier Transform Infrared (FTIR) spectroscopy. Degradation studies, performed in water via Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), showed that phosphates, Ca2+, Na+ and Cu ions are released in a controlled manner over a 7 days period. The controlled release of Cu, proportional to the copper loading, imbues antibacterial properties to MPG. A significant statistical reduction of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial viability was observed over a 3 days period. E. coli appeared to be more resistant than S. aureus to the antibacterial effect of copper. This study shows that copper doped MPG have great potential as bioresorbable materials for controlled delivery of antibacterial ions.

Mesoporous Phosphate-Based Glasses Prepared via Sol-Gel.

In the present study, a mesoporous phosphate-based glass (MPG) in the P2O5-CaO-Na2O system was synthesized, for the first time, using a combination of sol-gel chemistry and supramolecular templating. A comparison between the structural properties, bioactivity, and biocompatibility of the MPG with a non-porous phosphate-based glass (PG) of analogous composition prepared via the same sol-gel synthesis method but in the absence of a templating surfactant is also presented. Results indicate that the MPG has enhanced bioactivity and biocompatibility compared to the PG, despite having a similar local structure and dissolution properties. In contrast to the PG, the MPG shows formation of hydroxycarbonate apatite (HCA) on its surface after 24 h of immersion in simulated body fluid. Moreover, MPG shows enhanced viability of Saos-2 osteosarcoma cells after 7 days of culturing. This suggests that textural properties (porosity and surface area) play a crucial role in the kinetics of HCA formation and in interaction with cells. Increased efficiency of drug loading and release over non-porous PG systems was proved using the antibiotic tetracycline hydrochloride as a drug model. This study represents a significant advance in the field of mesoporous materials for drug delivery and bone tissue regeneration as it reports, for the first time, the synthesis, structural characterization, and biocompatibility of mesoporous calcium phosphate glasses.

Antibacterial silver-doped phosphate-based glasses prepared by coacervation.

Phosphate-based glasses are materials of great interest for the regeneration and repair of damaged hard or soft tissues. They have the desirable property of slowly dissolving in the physiological environment, eventually being totally replaced by regenerated tissue. Being bioresorbable, they can simultaneously induce tissue regeneration and deliver therapeutic agents (e.g. antibacterial ions) in a controlled way. In this work, we have synthesised a series of glasses in the P2O5-CaO-Na2O system doped with Ag2O using the coacervation method. The addition of silver is known to provide the glass with antibacterial properties due to the release of Ag+ ions into the body fluid. The coacervation method is a facile, water-based technique which offers significant advantages over the conventional melt-quench route for preparing phosphate-based glasses which requires melting of metal oxide powders at high temperatures (1000-1200 °C). The properties of the initial colloidal polyphosphate systems (coacervates) as a function of the Ag2O content were characterised using rheology and liquid state 31P NMR. The effect of Ag+ addition on the final dried glasses was investigated using thermal analysis, Raman spectroscopy and X-ray diffraction. The antibacterial activity was assessed against Staphylococcus aureus (S. aureus), a bacterial strain commonly found in post-surgery infections. A dose-dependent antimicrobial effect was seen with an increasing silver content.

Antibacterial Copper-Doped Calcium Phosphate Glasses for Bone Tissue Regeneration.

Calcium phosphate glasses are a promising new generation of biomaterials that can simultaneously induce tissue regeneration and controlled release of therapeutic molecules. In this work, novel calcium phosphate glasses containing 0, 2, 4, and 6 mol % Cu2+ were synthesized via room temperature precipitation reaction in aqueous solution. The effect of Cu2+ addition on the glass properties and structure was investigated using thermal analysis, 31P solid-state MAS NMR, Raman spectroscopy, and X-ray diffraction. All glasses crystallize at temperature >500 °C and are mainly formed by Q1 groups. The release of P, Ca, and Cu in solution over time was monitored via inductively coupled plasma-optical emission spectroscopy. It was found that with increasing Cu content, the amount of P and Ca released decreases whereas the amount of Cu released increases. The effect of Cu2+ release on the antibacterial activity against S. aureus, a bacterial strain commonly found in postsurgery infections, has been investigated. The addition of copper has been shown to infer the glasses antibacterial properties. As expected, the antibacterial activity of the glasses increases with increasing Cu2+ content. Cytocompatibility was assessed by seeding human osteoblast-like osteosarcoma cells Saos-2 (HTB85) on the glass particles. A significant increase in cell number was observed in all the glasses investigated. The copper-doped calcium phosphate glasses have proven to be multifunctional, as they combine bone regenerative properties with antibacterial activity. Therefore, they have great potential as antibacterial bioresorbable materials for hard tissue regeneration.