Biological evaluation of alginate-based hydrogels, with antimicrobial features by Ce(III) incorporation, as vehicles for a bone substitute

In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HA. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca2+ ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 hours at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HA, particularly the hydrogel Alg/HA.The authors would like to acknowledge the financial support from FCT (Fundacao para a Ciencia e a Tecnologia) through the grant SFRH/BD/76237/2011 and project ENMED/0002/2010, from FEDER funds through the program COMPETE-Programa Operacional Factores de Competitividade-under the project PEst-C/EME/UI0285/2011, as well as to the project I&DT BIOMAT&CELL n. 1372

Effect of the ultrastructure of chitosan nanoparticles in colloidal stability, quorum quenching and antibacterial activities

We have fabricated two types of crosslinked chitosan-based nanoparticles (NPs), namely (1) ionically crosslinked with tripolyphosphate (TPP), designated as IC-NPs and (2) dually co-crosslinked (ionically and covalently with TPP and genipin, respectively) termed CC-NPs. The two types of NPs were physichochemically characterized by means of DLS-NIBS, synchrotron SAXS and M3-PALS (zeta potential). First, we found that covalent co-crosslinking of ionically pre-crosslinked nanoparticles yielded monodisperse CC-NPs in the size range of ∼200 nm, whereas the parental IC-NPs remained highly polydisperse. While both types of chitosan nanoparticles displayed a core-shell structure, as determined by synchrotron SAXS, only the structure of CC-NPs remained stable at long incubation times. This enhanced structural robustness of CC-NPs was likely responsible of their superior colloidal stability even in biological medium. Second, we explored the antimicrobial and quorum sensing inhibition activity of both types of nanoparticles. We found that CC-NPs had lower long-term toxicity than IC-NPs. In contrast, sub-lethal doses of IC-NPs consistently displayed higher levels of quorum quenching activity than CC-NPs. Thus, this work underscores the influence of the NP’s ultrastructure on their colloidal and biological properties. While the cellular and molecular mechanisms at play are yet to be fully elucidated, our results broaden the spectrum of use of chitosan-based nanobiomaterialsin the development of antibiotic-free approaches against Gram-negative pathogenic bacteria

Anti-Candida activity of antimicrobial impregnated central venous catheters

Abstract Background Whenever the rate of central line-associated bloodstream infections (CLABSIs) remains high even after the implementation of preventive strategies, the use of chlorhexidine/silver sulfadiazine (CSS) or minocycline/rifampin (MR)-impregnated central venous catheters (CVCs) is currently recommended. Nevertheless, the efficacy of such CVCs against Candida albicans and other emerging non-albicans spp. has been insufficiently studied. This study aims to compare the activity of CSS and MR-impregnated CVCs against the yeasts most frequently isolated from CLABSIs. Methods For biofilm formation assays, type strains and clinical isolates of C. albicans, C. glabrata and C. parapsilosis sensu stricto were used. Segments of standard polyurethane, MR and second-generation CSS-CVCs were tested. The biofilm metabolic activity was measured by a semi-quantitative XTT reduction assay. Results CSS catheter segments significantly reduced the biofilm metabolic activity by all tested Candida spp., with inhibition ranging from 60% to 100%. The MR catheter segments promoted C. albicans and C. parapsilosis biofilm formation and exhibited an inconspicuous effect against C. glabrata. Conclusions Among the recommended antimicrobial CVCs, CSS-CVCs proved to be superior in the inhibition of biofilm formation by the most frequent yeasts causing CLABSIs. Data from this in vitro study may suggest that patients at high risk for invasive candidosis could benefit from the use of CSS-CVCs