Physical, Mechanical, and Biological Properties of PMMA-Based Composite Bone Cement Containing Silver-Doped Bioactive and Antibacterial Glass Particles with Different Particles Sizes

Abstract: In the present work, antibacterial composite bone cement was designed by introducing a bioactive and antibacterial glass into a commercial formulation. The effect of glass particles’ addition on the curing parameters of the polymeric matrix was evaluated; moreover, the influence of the glass particle size on the glass dispersion, compressive and bending strength, bioactivity, and antibacterial effect was estimated. The results evidence a delay in the polymerization kinetics of the composite cement, which nevertheless complies with the requirements of the ISO standard. Morphological characterization provides evidence of good dispersion of the glass in the polymeric matrix and its exposition on the cement surface. The different glass grain sizes do not affect the composites’ bioactivity and compressive strength, while a slight reduction in bending strength was observed for samples containing glass powders with greater dimensions. The size of the glass particles also appears to have an effect on the antibacterial properties, since the composites containing larger glass particles do not produce an inhibition halo towards the S. aureus strain. The obtained results demonstrate that, by carefully tailoring the glass amount and size, a multifunctional device for artificial joint fixing, temporary prostheses, or spinal surgery can be obtained

Bioactive glasses with low Ca/P ratio and enhanced bioactivity

Three new silica-based glass formulations with low molar Ca/P ratio (2–3) have been synthesized. The thermal properties, the crystalline phases induced by thermal treatments and the sintering ability of each glass formulation have been investigated by simultaneous differential scanning calorimetry-thermogravimetric analysis (DSC-TG), X-ray diffraction (XRD) and hot stage microscopy (HSM). The glasses exhibited a good sintering behavior, with two samples achieving shrinkage of 85%–95% prior to crystallization. The bioactivity of the glasses in simulated body fluid (SBF) has been investigated by performing XRD and Fourier transform infrared spectroscopy (FTIR) on the samples prior and after immersion. The glasses with lower MgO contents were able to form a fully crystallized apatite layer after three days of immersion in simulated body fluid (SBF), while for the glass exhibiting a higher MgO content in its composition, the crystallization of the Ca–P layer was achieved after seven days. The conjugation of these properties opens new insights on the synthesis of highly bioactive and mechanically strong prosthetic materials

Effect of silver ion incorporation into a bioactive glass surface on the adsorption of albumin

Introduction Nowadays, bacterial infection is one of the major causes for orthopedic implants failure. While it is well known how to manufacture materials that are able to stimulate osseointegration and to firmly bond with the bone, the fight against pathogenic microorganisms is carried on mainly by antibiotics, with consequent problems of poorly localized actions and antibiotic-resistance. Therefore, novel antibacterial strategies have been deeply researched. Among those, incorporation of silver in biomaterials, such as bioactive glasses, is acknowledged as an effective way to reduce bacteria proliferation. Osseointegration of biomaterials is dependent on the surface properties of the implants and on the interactions with the biological environment. In particular, a protein layer is formed on the surface within minutes after the contact between the surface and the biological fluids and it will dictate how the cells will respond to the implanted foreign body. As consequence, it is important to understand how antibacterial modifications of bioactive materials affect their interactions with proteins. In this work, the adsorption of albumin was investigated onto a silica-based bioactive glass where silver ions were incorporated through ionic exchange (Ag-SBA2) in order to understand eventual differences with the untreated surface (SBA2)[1]. Experimental Methods SBA2 bioactive glass (mol %: 48% SiO2, 18% Na2O, 30% CaO, 3% P2O5, 0.43% B2O3, 0.57% Al2O3) was prepared via precursors melting and casting, cut into disks and grinded (up to 1000 grit). Ag-SBA2 was prepared by soaking glass slices for 1h in 0.03M AgNO3 solution. Protein adsorption was obtained by soaking the samples for 2h at 37°C in albumin solution in PBS, in near physiological conditions (20 mg/ml, pH 7.4). The glass substrates were characterized in terms of topography and roughness (SEM, AFM and confocal microscopy), chemical composition (EDS and XPS), surface charge and potential (solid surface zeta potential, Kelvin Probe Force Microscopy (KPFM)) and surface energy (contact angle, Owens-Wendt method). The adsorbed proteins were quantified by using different methods (BCA assay, fluorescent proteins and XPS) and the BSA layer was also imaged (fluorescent microscopy and KPFM). Substrate-protein interactions and albumin conformation were investigated, too (solid surface zeta potential and ATR-FTIR). Results and Discussion After silver incorporation, confirmed by chemical analysis, the surface properties of Ag-SBA2 were mostly similar to the undoped glass. In particular, topography and roughness were unchanged during soaking in the silver solution, as expected. Wettability and surface free energy, both the dispersive and polar components, were also similar between the two substrates. Instead, zeta potential titration curve showed that the incorporation of Ag3+ ions increased the surface potential, in particular around physiological pH (7.4). Quantification of adsorbed BSA showed that both surfaces adsorb a similar amount of albumin, with a little higher amount on Ag-SBA2. This can be possibly related to a couple of different factors: the high affinity of silver for proteins and the presence of a more positive charge on the surface, which is able to attract the negatively charged albumin. On both surfaces, albumin forms a complete and homogeneous layer, as detected by imaging techniques. Adsorption of proteins was confirmed also by zeta potential measurement on the surfaces, with a shift of the IEP of both glassestowards the IEP of albumin. Thanks to ATR-FTIR measurement, it was found that albumin retains more its native conformation on the undoped glass with respect to the silver containing glass, where a more disordered structure was found. This fact can be ascribed to a greater interaction between the proteins and the doped surface, due to the presence of metal ions and more positive charges. Conclusion In conclusion, even though the incorporation of silver ions in a bioactive glass surface does not affect surface properties that are usually addressed as pivotal in protein adsorption, such as roughness and surface energy, the presence of a more positive charge on the surface of the glass and affinity of proteins towards metallic ions seems to be enough to increase adsorption of albumin and strength of the protein-biomaterial interaction. The increased interaction with proteins may be beneficial for the cells response to antibacterial silver containing materials

Cu-doped bioactive glass with enhanced in vitro bioactivity and antibacterial properties

This work aimed to optimize, produce and characterize Cu-doped bioactive glasses which are antibacterial without the addition of antibiotics obtained via ion exchange in an aqueous solution. According to morphological, compositional and structural analyses, 0.001 M was selected as the most optimal concentration of the ion exchange solution. The doped glass was then compared to the undoped one to investigate the effect of Cu-doping on the glass surface composition and bioactivity. Cu-doping was found to enhance the bioactivity kinetics and the following hydroxyapatite formation, evidenced by X-ray diffraction, energy dispersive X-ray spectroscopy, and zeta potential measurements. Besides that, the zeta potential titration measurements confirmed that the Cu-doping did not alter the surface chemical stability of the glass both in the inflammatory and physiological pH range. Moreover, the leaching ability of Cu2+-ions, both in physiological and inflammatory-mimicking conditions, was measured, followed by an in-depth study of the antibacterial properties, using two protocols to distinguish between the antiadhesive, antibacterial, and antibiofilm effects. For both protocols, a reduction of metabolic activity and Colony-Forming Unit after 24 h against Staphylococcus aureus Multi-Drug resistance strain was evidenced. These results showed that Cu-doped glass could show potential as a bioactive and antibacterial surface for bone surgery applications

Tumor targeting by monoclonal antibody functionalized magnetic nanoparticles

Tumor-targeted drug-loaded nanocarriers represent innovative and attractive tools for cancer therapy. Several magnetic nanoparticles (MNPs) were analyzed as potential tumor-targeted drug-loaded nanocarriers after functionalization with anti-Met oncogene (anti-Met/HGFR) monoclonal antibody (mAb) and doxorubicin (DOXO). Their cytocompatibility, stability, immunocompetence (immunoprecipitation), and their interactions with cancer cells in vitro (Perl's staining, confocal microscopy, cytotoxic assays: MTT, real time toxicity) and with tumors in vivo (Perl's staining) were evaluated. The simplest silica- and calcium-free mAb-loaded MNPs were the most cytocompatible, the most stable, and showed the best immunocompetence and specificity. These mAb-functionalized MNPs specifically interacted with the surface of Met/HGFR-positive cells, and not with Met/HGFR-negative cells; they were not internalized, but they discharged in the targeted cells DOXO, which reached the nucleus, exerting cytotoxicity. The presence of mAbs on DOXO-MNPs significantly increased their cytotoxicity on Met/HGFR-positive cells, while no such effect was detectable on Met/HGFR-negative cells. Bare MNPs were biocompatible in vivo; mAb presence on MNPs induced a better dispersion within the tumor mass when injected in situ in Met/HGFR-positive xenotumors in NOD/SCID-γnull mice. These MNPs may represent a new and promising carrier for in vivo targeted drug delivery, in which applied gradient and alternating magnetic fields can enhance targeting and induce hyperthermia respectively

Fe-doped sol-gel glasses and glass-ceramics for magnetic hyperthermia

This work deals with the synthesis and characterization of novel Fe-containing sol-gel materials obtained by modifying the composition of a binary SiO2-CaO parent glass with the addition of Fe2O3. The effect of different processing conditions (calcination in air vs. argon flowing) on the formation of magnetic crystalline phases was investigated. The produced materials were analyzed from thermal (hot-stage microscopy, differential thermal analysis, and differential thermal calorimetry) and microstructural (X-ray diffraction) viewpoints to assess both the behavior upon heating and the development of crystalline phases. N2 adsorption–desorption measurements allowed determining that these materials have high surface area (40–120 m2/g) and mesoporous texture with mesopore size in the range of 18 to 30 nm. It was assessed that the magnetic properties can actually be tailored by controlling the Fe content and the environmental conditions (oxidant vs. inert atmosphere) during calcination. The glasses and glass-ceramics developed in this work show promise for applications in bone tissue healing which require the use of biocompatible magnetic implants able to elicit therapeutic actions, such as hyperthermia for bone cancer treatment

Injectable Osteoinductive bone cements

The present invention concerns an injectable composition for the use in bone-filling and bone-consolidation in surgery and therapy. In particular, the invention relates to the field of injectable bone cements, for both treating of factures caused by osteoporosis or trauma and filling gaps due, for example, to the decrease of bone mass after removal of tumors or cysts