Exploiting shape-selected iron oxide nanoparticles for the destruction of robust bacterial biofilms - active transport of biocides via surface charge and magnetic field control.

Biofilms that form on reusable medical devices are a cause of hospital acquired infections; however, sanitization of biofilms is a challenge due to their dense extracellular matrix. This work presents an innovative strategy using biocide-loaded iron oxide nanoparticles transported within the matrix via a magnetic field to eradicate biofilms. Results show that the active delivery of the biocide to underlying cells effectively penetrates the extracellular matrix and inactivates Methicillin resistant Staphylococcus aureus (MRSA) biofilms (responsible for several difficult-to-treat infections in humans). To optimize this treatment, the loading of spherical, cubic and tetrapod-shaped nanoparticles with a model biocide, CTAB (cetyltrimethylammonium bromide) was studied. Biocide loading was determined to be dependent on the shapes' surface charge density instead of the surface area, meaning that biocide attachment is greater for nanoparticles with sharp edges (e.g. cubes and tetrapods). These results can be used to optimize treatment efficacy, and help further understanding of biofilm and nanoparticle surface zeta potentials, and the nanoparticle-biofilm interactions.

Engineering Rechargeable Antibacterial Coatings on Stainless Steel for Efficient Inactivation of Pathogenic Bacteria in the Presence of Organic Matter.

Worldwide, around 600 million people are affected by foodborne illnesses each year which highlights the importance of food safety. It is important to ensure the cleanliness of the working surfaces in food processing facilities. Stainless steel is widely used in the food industry as a food contact surface. Endowing stainless steel with a potent rechargeable antibacterial function offers the prospect of a reusable and clean surface. In this study, a "clickable" coating for stainless steel was developed. Quaternized azido-hydantoin (C1), quaternary ammonium compound (C2), and azido-hydantoin (C3) were bonded to stainless steel primed with the clickable coating to yield three samples: SSMC1, SSMC2, and SSMC3, respectively. The coating was stable during the chlorination process which was used to convert the immobilized C1 and C3 to their N-chloramine counterparts (SSMC1-Cl and SSMC3-Cl, respectively). It was shown that SSMC1-Cl had the best antibacterial activity with 100% reduction of E. coli and S. aureus after 1 and 2 h of contact, respectively. SSMC1-Cl also showed the best performance in high protein medium (HPM) against bacteria, demonstrating 100% and 99.9% bacterial reduction against E. coli and S. aureus, respectively, after 3 h of contact. After five cycles of chlorination-dechlorination, SSMC1-Cl sustained a kill efficiency of 100% for both E. coli and S. aureus within 2 h of contact. This result reveals that SSMC1-Cl has the ability to maintain its antibacterial activity after repetitive cycles, which emphasizes its rechargeable nature. Altogether, this study presents an effective quaternized N-chloramine-based biocidal coating on stainless steel (SSMC1-Cl) that is rechargeable, durable, and effective against Gram-positive and Gram-negative bacteria.

Lipase-Responsive Electrospun Theranostic Wound Dressing for Simultaneous Recognition and Treatment of Wound Infection.

Simultaneous monitoring and treatment of wound infection is of great importance in the biomedical field. The present work describes the development of a theranostic wound dressing (TH-WD) that can monitor and inhibit wound infection simultaneously. The main component of TH-WD is a polyurethane (PU) scaffold loaded with a ciprofloxacin-based prodrug (Pro-Cip) and a chromogenic probe (H-Cy). In vitro studies demonstrated that TH-WD displayed efficient inactivation (100 ± 4% reduction) of Pseudomonas aeruginosa (ATCC 27853) within 4 h of contact while providing a visual detection of wound infection via a simple color change from yellow to green to red. These results are attributed to the activation of H-Cy and Pro-Cip via hydrolysis of their ester linkages catalyzed by lipase, an extracellular enzyme secreted by bacteria. Moreover, TH-WD is highly selective as it only changes color and releases the active drug (ciprofloxacin) in the presence of certain lipase-secreting pathogenic bacteria such as P. aeruginosa ATCC 27853, and no color change and cytotoxicity were observed when TH-WD was incubated with no- or low-lipase-producing bacteria (e.g., E. coli TOP 10) or skin cell fibroblast. This hence can minimize the emergence of bacterial resistance associated with the overuse of antibiotics and avoid unnecessary cytotoxicity to skin cells. The present system not only provides a visible and noninvasive method to monitor the wound status but also allows the timely administration of antibacterial agents to inactivate bacteria in the wound.

New Generation of N-Chloramine/QAC Composite Biocides: Efficient Antimicrobial Agents To Target Antibiotic-Resistant Bacteria in the Presence of Organic Load.

We previously reported that covalently joining an amide-based N-chloramine with a quaternary ammonium compound (QAC) can yield a new composite biocide with faster inactivation of various bacteria. Importantly, the composite biocide was found to reduce the risk for potential bacterial resistance associated with QAC. However, similar to other N-chloramines and QACs, this high-performance composite biocide becomes less potent against pathogenic bacteria in the presence of high protein fluids. In this study, we substituted the amide-based N-chloramine moiety in the previously reported composite biocide with a secondary amine-based N-chloramine to improve the biocidal efficacy in biological fluids. The N-Cl bond in the synthesized tetramethylpiperidine-based composite biocides is more stable in a high protein medium (HPM) than that in the hydantoin (amide)-based composite biocides. The composite biocide, 2-[4-(1-chloro-2,2,6,6-tetramethyl-piperidin-4-yloxymethyl)-[1,2,3]triazol-1-yl]-ethyl-dodecyl-dimethyl-ammonium chloride (6a), showed the best antibacterial activity in both phosphate-buffered saline and HPM among various composite biocides and benzyldodecyldimethylammonium chloride used in this study.

Preventing in-stent restenosis using lipoprotein (a), lipid and cholesterol adsorbent materials.

Atherosclerosis is one of the major cause of mortality in developed countries. The characteristic lesion of atherosclerosis is the atheroma or plaque that forms through thickening of the inner layer of the vessel wall (called the intima). The development of stent in 1980s revolutionised treatment of cardiovascular diseases, including atherosclerosis. However the advent of stenting was hindered by the new problem of in-stent restenosis. It was demonstrated that in-stent restenosis was the result of a new pathology in the form of neointimal hyperplasia, which was a maladaptive healing response to bare-metal stent implantation. Recent evidence suggests that although drug-eluting stent (DES) have reduced restenosis rates, important concerns have been raised regarding increased late stent thrombosis, myocardial infarction and death. With advances in nanotechnology and smart materials, covered stents has been proposed to overcome this problem. This is due to in-stent late restenosis and thromboses are mainly caused by smooth muscle cells (SMC) proliferation. Studies showed that there is a relation between high low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] level in blood stream and chance of in-stent restenosis, moreover studies show that Lp(a) could stimulate SMC proliferation. We hypothesis development of covered stent with novel design and use of smart materials which could adsorb cholesterol and prevent contact between Lp(a) and vessel wall to overcome problem indicated in DES. In addition cost of stents will significantly reduce by elimination of drugs as well as complex manufacturing of the drug incorporation.