New solutions for combatting implant bacterial infection based on silver nano-dispersed and gallium incorporated phosphate bioactive glass sputtered films:A preliminary study

Ag/Ga were incorporated into resorbable orthopaedic phosphate bioactive glasses(PBG,containing P,Ca,Mg,Na,and Fe)thin films to demonstrate their potential to limit growth of Staphylococcus aureus and Escherichia coli in post-operative prosthetic implantation.Dual target consecutive co-sputtering was uniquely employed to produce a 46 nm Ag:PBG composite observed by high resolution TEM to consist of uniformly dispersed~5 nm metallic Ag nano-particles in a glass matrix.Ga^(3+)was integrated into a phosphate glass preform target which was magnetron sputtered to film thicknesses of~400 or 1400 nm.All coatings exhibited high surface energy of 75.4-77.3 mN/m,attributed to the presence of hydrolytic P-O-P structural surface bonds.Degradation profiles obtained in deionized water,nutrient broth and cell culture medium showed varying ion release profiles,whereby Ga release was measured in 1400 nm coating by ICP-MS to be~6,27,and 4 ppm respectively,fully dissolving by 24 h.Solubility of Ag nanoparticles was only observed in nutrient broth(~9 ppm by 24 h).Quantification of colony forming units after 24 h showed encouraging antibacterial efficacy towards both S.aureus(4-log reduction for Ag:PBG and 6-log reduction for Ga-PBG≈1400 nm)and E.coli(5-log reduction for all physical vapour deposited layers)strains.Human Hs27 fibroblast and mesenchymal stem cell line in vitro tests indicated good cytocompatibility for all sputtered layers,with a marginal cell proliferation inertia in the case of the Ag:PBG composite thin film.The study therefore highlights the(i)significant manufacturing development via the controlled inclusion of metallic nanoparticles into a PBG glass matrix by dual consecutive target co-sputtering and(ii)potential of PBG resorbable thin-film structures to incorporate and release cytocompatible/antibacterial oxides.Both architectures showed prospective bio-functional performance for a future generation of endo-osseous implant-type coatings.

Independent and complementary bio-functional effects of CuO andGa_(2)O_(3) incorporated as therapeutic agents in silica-and phosphate-based bioactive glasses

The incorporation of therapeutic-capable ions into bioactive glasses(BGs),either based on silica(SBGs)or phosphate(PBGs),is currently envisaged as a proficient path for facilitating bone regeneration.Inconjunction with this view,the single and complementary structural and bio-functional roles of CuO andGa_(2)O_(3)(in the 2e5 mol%range)were assessed,by deriving a series of SBG and PBG formulations startingfrom the parent glass systems,FastOs®BG e 38.5SiO2d36.1CaOd5.6P2O5d19.2MgOd0.6CaF2,and50.0P2O5d35.0CaOd10.0Na_(2)Od5.0 Fe2O_(3)(mol%),respectively,using the process of melt-quenching.The inter-linked physico-chemistry e biological response of BGs was assessed in search of bio-functional triggers.Further light was shed on the structural role e as network former or modifier e ofCu and Ga,immersed in SBG and PBG matrices.The preliminary biological performance was surveyedin vitro by quantification of Cu and Ga ion release under homeostatic conditions,cytocompatibility assays(in fibroblast cell cultures)and antibacterial tests(against Staphylococcus aureus).The similar(Cu)anddissimilar(Ga)structural roles in the SBG and PBG vitreous networks governed their release.Namely,Cuions were leached in similar concentrations(ranging from 10e35 ppm and 50e110 ppm at BG doses of 5and 50 mg/mL,respectively)for both type of BGs,while the release of Ga ions was 1e2 orders ofmagnitude lower in the case of SBGs(i.e.,0.2e6 ppm)compared to PBGs(i.e.,9e135 ppm).This wasattributed to the network modifier role of Cu in both types of BGs,and conversely,to the network former(SBGs)and network modifier(PBGs)roles of Ga.All glasses were cytocompatible at a dose of 5 mg/mL,while at the same concentration the antimicrobial efficiency was found to be accentuated by the coupledrelease of Cu and Ga ions from SBG.By collective assessment,the most prominent candidate material forthe further development of implant coatings and bone graft substitutes was delineated as the38.5SiO2d34.1CaOd5.6P2O5d16.2MgOd0.6CaF2d2.0CuOd3.0Ga_(2)O_(3)(mol%)SBG system,which yiel-ded moderate Cu and Ga ion release,excellent cytocompatibility and marked antibacterial efficacy.