Multifunctional Glyco-Nanosheets to Eradicate Drug-Resistant Bacteria on Wounds.

Bacterial infection is becoming increasingly lethal with the emergence of antimicrobial resistance, and wounds plagued by such infection are notoriously difficult to heal. Here, the first use of galactose-black phosphorus nanosheets, (Gal-BP NSs) as a delivery platform for synergistic antibiotic (kanamycin, Kana) and photothermal treatments against the Gram-negative microbial strain, Pseudomonas aeruginosa PAO1 (PAO1) is reported. Gal-BP NSs@Kana can actively target PAO1 and release kanamycin into the bacterial cytoplasm upon near-infrared laser irradiation. This strategy kills most of the PAO1 through a simultaneous burst of intracellular kanamycin release and photothermal treatment. Comparable antibacterial activities of Gal-BP NSs@Kana are observed within in vivo mouse models at their wound sites. In addition, this platform accelerates wound healing from PAO1 infection via promotion of neoangiogenesis and collagen production at the wound sites. This work demonstrates the material properties of Gal-BP NS in fighting bacterial infections and in the treatment of wound healing.

Biguanide-Derived Polymeric Nanoparticles Kill MRSA Biofilm and Suppress Infection In Vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of drug-resistant infections. Its propensity to develop biofilms makes it especially resistant to conventional antibiotics. We present a novel nanoparticle (NP) system made from biocompatible F-127 surfactant, tannic acid (TA), and biguanide-based polymetformin (PMET) (termed FTP NPs), which can kill MRSA biofilm bacteria effectively in vitro and in vivo and which has excellent biocompatibility. FTP NPs exhibit biofilm bactericidal activity-ability to kill bacteria both inside and outside biofilm-significantly better than many antimicrobial peptides or polymers. At low concentrations (8-32 µg/mL) in vitro, FTP NPs outperformed PMET with ∼100-fold (∼2 log10) greater reduction of MRSA USA300 biofilm bacterial cell counts, which we attribute to the antifouling property of the hydrophilic poly(ethylene glycol) contributed by F-127. Further, in an in vivo murine excisional wound model, FTP NPs achieved 1.8 log10 reduction of biofilm-associated MRSA USA300 bacteria, which significantly outperformed vancomycin (0.8 log10 reduction). Moreover, in vitro cytotoxicity tests showed that FTP NPs have less toxicity than PMET toward mammalian cells, and in vivo intravenous injection of FTP NPs at 10 mg/kg showed no acute toxicity to mice with negligible body weight loss and no significant perturbation of blood biomarkers. These biguanide-based FTP NPs are a promising approach to therapy of MRSA infections.

In Vivo Anti-Biofilm and Anti-Bacterial Non-Leachable Coating Thermally Polymerized on Cylindrical Catheter.

Catheters are indispensable tools of modern medicine, but catheter-associated infection is a significant clinical problem, even when stringent sterile protocols are observed. When the bacteria colonize catheter surfaces, they tend to form biofilms making them hard to treat with conventional antibiotics. Hence, there is a great need for inherently antifouling and antibacterial catheters that prevent bacterial colonization. This paper reports the preparation of nonleachable antibiofilm and antibacterial cationic film coatings directly polymerized from actual tubular silicone catheter surfaces via the technique of supplemental activator and reducing agent surface-initiated atom-transfer radical polymerization (SARA SI-ATRP). Three cross-linked cationic coatings containing (3-acrylamidopropyl) trimethylammonium chloride (AMPTMA) or quaternized polyethylenimine methacrylate (Q-PEI-MA) together with a cross-linker (polyethylene glycol dimethacrylate, PEGDMA) were tested. The in vivo antibacterial and antibiofilm effect of these nonleachable covalently linked coatings (using a mouse catheter model) can be tuned to achieve 1.95 log (98.88%) reduction and 1.26 log (94.51%) reduction of clinically relevant pathogenic bacteria (specifically with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE)). Our good in vivo bactericidal killing results using the murine catheter-associated urinary tract infection (CAUTI) model show that SARA SI-ATRP grafting-from technique is a viable technique for making nonleachable antibiofilm coating even on "small" (0.30/0.64 mm inner/outer diameter) catheter.

Density quantification of collagen grafted on biodegradable polyester: its application to esophageal smooth muscle cell.

An improved technique for quantification of collagen immobilized on polymeric substrates is needed as tissue engineering evolves. Current immobilized protein quantification methods are indirect, time-consuming, and/or inaccurate. In this study, Sirius red colorimetric microassay was shown to be feasible for quantifying the density of collagen immobilized on aminolyzed poly(L-lactic acid) (PLLA) surfaces using the specific bonding of Sirius dye to collagen. It offers a number of advantages over traditional methods, including direct staining, high sensitivity, and high stability of the dye. The detection limit is approximately 0.1 microg/cm(2), and the dynamic range is greater than 50. Sirius red dye has not been used previously for quantification of protein immobilized on polymers. The collagen densities achieved with each of the two crosslinking reagents investigated, namely glutaraldehyde (GA) and genipin, were compared. The latter is an alternative crosslinker derived from a traditional Chinese medicine. The collagen densities immobilized by the two reagents were measured to be similar. This was confirmed by the similar behaviors of esophageal primary smooth muscle cells (ESMCs) on these two modified PLLA membranes; collagen grafted with either coupler was found to greatly promote, to a similar extent, cell attachment and both short-term (4 days) and long-term (12 days) proliferation compared with unmodified PLLA. Smooth muscle cells on both modified membranes were stained to display contractile alpha-actin protein filaments.