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Photodynamic therapy (PDT) is an effective non-invasive or minimally invasive treatment method against different tumors. Loading photosensitizers in nanocarriers can potentially increase their accumulation in tumor sites. However, the PDT efficacy may be hindered because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Herein, light responsive nano assemblies composed of (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) were designed and loaded with the photosensitizer, Rose Bengal lactone (RB), to act as a smart nanocarrier (RB-M) for the delivery of the photosensitizer. A wirelessly activated light-emitting diode (LED) implant was designed to programmatically induce the release of the loaded RB first, followed by activating PDT after diffusion of RB into the cytoplasm. The results showed that sequential '405-580 nm' irradiation of the RB-M treated 22RV1 cells resulted in the highest PDT outcome among different irradiation protocols. The combination of this smart nanocarrier and sequential '405-580 nm' irradiation strategy exhibited good PDT efficacy against 2D 22RV1 prostate cancer cells as well as 3D cancer cell spheroids. This platform overcomes the light penetration limitations in PDT, and can potentially be applied in cancer bearing patients who are unfit for chemotherapy. STATEMENT OF SIGNIFICANCE: Nanocarriers for the delivery of photosensitizer in photodynamic therapy may result in relatively low therapeutic efficacy because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Light responsive smart nanocarriers can potentially overcome this challenge. In this study, a light responsive polymer (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) was synthesized and utilized to fabricate the smart nanocarrier. A wirelessly activated light-emitting diode (LED) implant was designed for light delivery in deep tissue. This new approach permits wirelessly and programmatically control of photosensitizer release and PDT activation under deep tissue, thus significantly enhancing PDT efficacy against prostate cancer cells as well as 3D cancer cell spheroids. This design should have a significant impact on controllable PDT under deep tissue., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC 50 of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Detection of non-muscle invasive bladder cancer (NMIBC) is crucial to facilitate complete tumor resection, thus improving the survival rate as well as reducing the recurrence frequency and treatment expense. Fluorescence imaging cystoscopy is an effective method for the detection of NMIBC. However, its application is limited as the commonly applied fluorescent agents such as dyes and photosensitizers usually lack specific tumor accumulation and are vulnerable to photobleaching. Furthermore, the broad emission band of conventional fluorescent agents limits their imaging and detection efficacy. To overcome these limitations, upconversion nanoparticles (UCNPs) have been selected as the fluorescent agent, due to their resistance to photobleaching, less background auto-fluorescence, and narrow emission bands. In order to achieve active tumor targeting, the UCNPs are coated with a glycosylated phospholipid layer. The glycosylated phospholipid-coated UCNPs exhibited high selective accumulation in cancer cells over normal cells and enhanced the upconversion luminescence (UCL) (at 540 nm and 660 nm) from bladder cancer cells under 980 nm laser irradiation. Glycosylated phospholipid coating that promotes uptake of UCNPs by cancer cells, and UCL emitted from UCNPs under NIR (980 nm) laser irradiation for cancer cell imaging., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Photochemical internalization (PCI) is a promising intervention using photodynamic therapy (PDT) to enhance the activity of chemotherapeutic drugs. However, current bladder cancer treatments involve high-dose chemotherapy and high-irradiance PDT which cause debilitating side effects. Moreover, low penetration of light and drugs in target tissues and cumbersome light delivery procedures hinder the clinical utility of PDT and chemotherapy combination for PCI. To circumvent these challenges, a photodynamic-chemotherapy approach is developed comprising tumor-targeting glycosylated nanocarriers, coloaded with chlorin e6 (Ce6) and gemcitabine elaidate (GemE), and a miniaturized implantable wirelessly powered light-emitting diode (LED) as a light source. The device successfully delivers four weekly light doses to the bladder while the nanocarrier promoted the specific accumulation of drugs in tumors. This approach facilitates the combination of low-irradiance PDT (1 mW cm -2 ) and low-dose chemotherapy (≈1500× lower than clinical dose) which significantly cures and controls orthotopic disease burden (90% treated vs control, 35%) in mice, demonstrating a potential new bladder cancer treatment option., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The occurrence of emerging organic contaminants (EOCs) such as chemicals in personal care products, pharmaceuticals, plasticizers, etc. in surface waters is a growing global concern. The discharge of most EOCs is not regulated, and EOCs have been shown to be toxic to both human and aquatic life even at low concentrations. In this work, acid-leached carbon black waste (LCBW), a carbonaceous residue from petroleum refineries, was investigated as a potential waste-derived adsorbent for the removal of EOCs. Ciprofloxacin hydrochloride, (CIPRO, antibiotic), sulfamethoxazole (SULFA, antibiotic), acetaminophen (ACET, pharmaceutical), bisphenol A (BPA, plasticizer) and N,N-diethyl-3-methylbenzamide (DEET, insect repellent) were chosen as the target EOCs owing to their presence in relatively high concentrations in surface waters as well as in the influent and effluent of wastewater treatment plants. LCBW, with a specific surface area of 409 m 2 /g, demonstrated 90-99% removal of 10 ppm CIPRO, BPA, and ACET and 70-80% removal of 10 ppm SULFA and DEET in tap water. Adsorption was rapid, particularly for CIPRO, BPA, and ACET, wherein >85% of the adsorption occurred within 1 h of contact time. To illustrate the potential of LCBW as an adsorbent in different physical forms, ∼3 mm spherical beads of LCBW encapsulated within carboxymethyl cellulose matrix were prepared by a facile ionic gelation method and their adsorption performance was demonstrated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Surface contamination by microbes leads to several detrimental consequences like hospital- and device-associated infections. One measure to inhibit surface contamination is to confer the surfaces with antimicrobial properties. Copper's antimicrobial properties have been known since ancient times, and the recent resurgence in exploiting copper for application as antimicrobial materials or coatings is motivated by the growing concern about antibiotic resistance and the pressure to reduce antibiotic use. Copper, unlike silver, demonstrates rapid and high microbicidal efficacy against pathogens that are in close contact under ambient indoor conditions, which enhances its range of applicability. This review highlights the mechanisms behind copper's potent antimicrobial property, the design and fabrication of different copper-based antimicrobial materials and coatings comprising metallic copper/copper alloys, copper nanoparticles or ions, and their potential for practical applications. Finally, as the antimicrobial coatings market is expected to grow, we offer our perspectives on the implications of increased copper release into the environment and the potential ecotoxicity effects and possibility of development of resistant genes in pathogens.

Intravesical chemotherapy for bladder cancer has limited efficacy due to the lack of specificity of drugs/drug carriers toward the cancer cells as well as inadequate drug residence time in the bladder due to urine voiding. From analyses of surface receptor expression of UMUC3 bladder cancer cells and the targeting efficacy of different peptides, we selected a peptide (txCD47) that targets the cluster of differentiation 47 (CD47) surface protein overexpressed on these cells as a targeting ligand for docetaxel (DTX) and an albumin nanocarrier of DTX. The IC 50 of DTX conjugated to txCD47 (txCD47-DTX) in a 1:1 molar ratio was lowered by a factor of 3 from that of free DTX. By using the albumin molecule (txCD47-BSA) as a delivery vehicle, different amounts of txCD47 can be conjugated to investigate the effects of peptide concentration on targeting efficacy. The IC 50 of DTX loaded in txCD47-BSA with 14 txCD47 per albumin molecule was 1 order of magnitude lower than that of free DTX, and a factor of 4 lower than that of txCD47-BSA with 8 txCD47 per albumin molecule. DTX was released from the albumin nanocarrier at a controlled rate, and the endocytosed carrier will release most of its payload inside the cells within 72 h. Thus, txCD47 promotes delivery of the drug/drug carrier, and the resultant enhanced killing efficacy of the drug can potentially alleviate some of the limitations of intravesical chemotherapy against bladder cancer.

Bacterial biofilms cause chronic infections due to their inherent tolerance to antimicrobial therapies. We describe and compare the efficacy of two types of sugar (d-glucose and d-mannose)-modified cyclodextrin nanocarriers (CD-GLU and CD-MAN) loaded with antibacterial agents for preventing and eradicating bacterial biofilm. The antibacterial agents comprise a quorum sensing inhibitor (5,6-dimethyl-2-aminobenzimidazole, DMABI) and two antibiotics (erythromycin and rifampicin), and the cyclodextrin nanocarriers were tested on Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive). DMABI loaded in the CD-GLU carrier was significantly more effective at inhibiting the development of Pseudomonas aeruginosa biofilm when compared to either its free form or when it is loaded in CD without grafted sugar moieties. Antibiotics loaded in CD-GLU and CD-MAN carriers were similarly more effective at dispersing pre-formed Pseudomonas aeruginosa biofilms. These antibacterial compounds loaded in the CD-GLU and CD-MAN carriers were somewhat less effective in eradicating Staphylococcus aureus biofilm as compared to Pseudomonas aeruginosa biofilm. This difference is attributed to the different extent of penetration of the sugar-grafted carriers into the biofilms of these two species of bacterial cells. Although the sugar-grafted carrier-antibacterial agent complexes exhibit potent effects against bacterial biofilms, they are not cytotoxic to mammalian cells.

Urine voiding and the presence of a mucus layer on the apical surface of the urothelium are two major challenges towards an effective intravesical drug delivery for bladder malignancies. Improved bioavailability to the underlying bladder tissue could be achieved with delivery vectors that diffuse efficiently through the bladder mucus. Pegylation of delivery vectors remains the existing "gold standard" to enhance mucosal delivery despite known poor cell uptake and reported PEG sensitivity. Here, we showed improved mucopenetration of carboxylated polystyrene (PS) nanoparticles (NPs) passivated with a polydopamine (PDA) surface, at similar level as PEG. While the diffusion of PS NPs in mucus was retarded by ~1000-fold, PS-PDA diffused only 6-fold slower in mucus than water. This enabled faster and deeper penetration of PS-PDA into porcine bladder tissue beneath the mucus layer. The same PDA surface also conferred biocompatibility and enabled photothermal therapy (PTT) with significant surface disruption on an ex vivo porcine bladder model upon localized laser irradiation, which was not possible with PEG. Our outcomes suggested the facile and versatile PDA surface passivation of nanoparticles as an enabler for dual purposes of enhancing mucopenetration and allowing photothermal therapy on bladder tissue, which has not been demonstrated to date., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mucus is an endogenous viscoelastic biopolymer barrier that limits the entry of foreign pathogens and therapeutic carriers to the underlying mucosal cells. This could be overcome with a hydrophilic and nonpositively charged carrier surface that minimizes interactions with the mucin glycoprotein fibers. Although PEGylation remains an attractive surface strategy to enhance mucopenetration, cell uptake of PEGylated nanoparticles (NPs) often remains poor. Here, we demonstrated polydopamine (PDA) coating to enhance both mucopenetration and cell uptake of NPs. PDA was polymerized on carboxylated polystyrene (PS) NPs to form a PDA coating, and the resulting PS-PDA achieved a similar level of mucopenetration as our PEGylated PS (PS-PEG) positive control in three separate studies: NP-mucin interaction test, transwell assay, and multiple particle tracking. Compared to water, the diffusions of PS-PDA and PS-PEG in reconstituted mucus solution were only 3.5 and 2.4 times slower, respectively, whereas the diffusion of bare PS was slowed by up to 250 times. However, the uptake of PS-PDA (61.2 ± 6.1%) was almost three times higher than PS-PEG (24.6 ± 5.4%) in T24 cells, which were used as a model for underlying mucosal cells. Our results showed a novel unreported functionality of PDA coating in enhancing both mucopenetration and cell uptake of NPs for mucosal drug delivery applications, not possible with conventional PEGylation strategies.

Bacterial surface contamination is a major cause of hospital-associated infections. Antibacterial coatings can play an important role in reducing bacterial transmission via inanimate surfaces in healthcare settings. In this work, transparent copper-based antibacterial coatings were fabricated on commercial poly(vinyl fluoride) and stainless steel. Acrylated quaternized chitosan and ethylenediaminetetraacetic acid were covalently grafted on the substrate for complexation with copper ions. The number of viable Staphylococcus aureus in a droplet [containing ∼10 4 colony forming units (CFU)], deposited on the copper-containing coating decreased by ∼96% within 60 min at 25 °C. With Pseudomonas aeruginosa, one of the most virulent and hardest to kill bacteria, no CFU could be observed within the same time span (killing efficacy >99.8% based on the detection limit). An increase in copper release from the coating was observed in the presence of P. aeruginosa, which was postulated to be due to the proteolytic activity of P. aeruginosa. The higher efficacy of the coating against P. aeruginosa compared to S. aureus is thus attributed to this increased copper release from the coating, which resulted in extensive bacterial membrane damage and death. The copper-containing coating on poly(vinyl fluoride) retained its antibacterial efficacy after 100 wipes with a water-wetted cloth or isopropanol wipes, demonstrating its durability and long-term efficacy. The coating did not exhibit significant cytotoxicity toward mammalian fibroblasts, further demonstrating its potential for mitigating bacterial transmission in a clinical setting.

Background: Catheter Associated Urinary Tract Infections are among the most common urological infections world-wide. Bacterial biofilms and encrustation cause significant complications in patients with urinary catheters. The objective of the study is to demonstrate the efficacy and safety of an anti-microbial and anti-encrustation silver nanoparticle (AgNP) coating on silicone urinary catheter in two different animal models., Methods: Antifouling coating (P3) was prepared with alternate layers of polydopamine and AgNP and an outermost antifouling layer. Sixteen C57BL/6 female mice and two female PWG Micropigs® were used to perform the experiments. In mice, a 5 mm long silicone catheter with or without P3 was transurethrally placed into the urinary bladder. Micropigs were transurethrally implanted - one with P3 silicone catheter and the other with commercially available silver coated silicone catheter. Both models were challenged with E. coli. Bacteriuria was evaluated routinely and upon end of study (2 weeks for mice, 3 weeks for micropigs), blood, catheters and bladders were harvested and analysed for bacterial colonization and encrustation as well as for toxicity., Results: Lower bacterial colonization was seen on P3 catheters as well as in bladders of animals with P3 catheter. Bacteriuria was consistently less in mice with P3 catheter than with uncoated catheters. Encrustation was lower on P3 catheter and in bladder of micropig with P3 catheter. No significant toxicity of P3 was observed in mice or in micropig as compared to controls. The numbers were small in this proof of concept study and technical issues were noted especially with the porcine model., Conclusions: Antifouling P3 coating reduces bacterial colonization on catheter and in animal bladders without causing any considerable toxicity for 2 to 3 weeks. This novel coating could potentially reduce the complications of indwelling urethral catheters.

Our study shows a facile two-step method which does not require the use of core templates to load a hydrophobic photosensitizer drug chlorin e6 (Ce6) within polydopamine (PDA) nanoparticles (NPs) while maintaining the intrinsic surface properties of PDA NPs. This structure is significantly different from hollow nanocapsules which are less stiff as they do not possess a core. To our knowledge, there exist no similar studies in the literature on drug loading within the polymer matrix of PDA NPs. We characterized the drug loading and release behavior of the photosensitizer Ce6 and demonstrated the therapeutic efficacy of the combined photodynamic (PDT) and photothermal therapy (PTT) from Ce6 and PDA, respectively, under a single wavelength of 665 nm irradiation on bladder cancer cells. We obtained a saturated loading amount of 14.2 ± 0.85 μM Ce6 in 1 nM PDA NPs by incubating 1 mg/mL dopamine solution with 140 μM of Ce6 for 20 h. The PDA NPs maintained colloidal stability in biological media, whereas the pi-pi (π-π) interaction between PDA and Ce6 enabled a release profile of the photosensitizer until day 5. Interestingly, loading of Ce6 in the polymer matrix of PDA NPs significantly enhanced the cell uptake because of endocytosis. An increased cell kill was observed with the combined PDT + PTT from 1 nM PDA-Ce6 compared to that with PTT alone with 1 nM PDA and PDT alone with 15 μM equivalent concentration of free Ce6. PDA-Ce6 NPs could be a promising PDT/PTT therapeutic agent for cancer therapy.

Bacterial biofilms are responsible for the failure of many medical devices such as urinary catheters and are associated with many infectious and non-infectious complications. Preclinical and clinical evaluation of novel catheter coatings to prevent these infections needs to accurately quantify the bacterial load in the biofilm in vitro and ex vivo. There is currently no uniform gold standard for biofilm quantification for different surfaces and established biofilms. We have tried to establish a simple, accurate and reproducible method for extraction and measurement of biofilm bacteria on indwelling catheters, using a combination of vortexing and sonication. We demonstrate the usefulness of this method for catheters of different sizes - 3 Fr to 14 Fr - in vitro, in murine and porcine models, and indwelling in human clinical subjects. We also demonstrate consistent results with complex and polymicrobial biofilms. We believe that this standardized reproducible method will assist the assessment of biofilms in general and urological devices in particular in efforts to harness novel technologies to prevent healthcare associated infections.

Electrical stimulation (ES) has emerged as a useful tool to regulate cell behaviour, but the effect of ES on mesenchymal stem cell (MSC)/vasculogenic cell co-culture has not been investigated. Herein, human adipose-derived MSCs (AD-MSCs) and umbilical vein endothelial cells (HUVECs) were co-cultured in an electrically conductive polypyrrole/chitosan scaffold. Compared with AD-MSC monoculture, calcium deposition in the co-culture without and with ES (200 μA for 4 h/day) was 139% and 346% higher, respectively, after 7 days. As the application of ES to AD-MSC monoculture only increased calcium deposition by 56% compared with that without ES after 7 days, these results indicate that ES and co-culture with HUVECs have synergistic effects on AD-MSCs' osteogenic differentiation. ES application also significantly enhanced CD31 expression of HUVECs. In HUVEC monoculture, application of ES increased CD31 expression by 224%, whereas the corresponding increase in AD-MSC/HUVEC co-culture with ES application was 62%. The gene expression results indicate that ES enhanced the cellular functions in AD-MSC and HUVEC monoculture via autocrine bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), respectively. In co-culture, crosstalk between AD-MSCs and HUVECs due to paracrine BMP-2 and VEGF enhanced the cellular functions compared with the respective monoculture. With application of ES to the AD-MSC/HUVEC co-culture, autocrine signalling was enhanced, resulting in further promotion of cellular functions. These findings illustrate that co-culturing AD-MSC/HUVEC in a conductive scaffold with ES offers potential benefits for bone defect therapy., (Copyright © 2017 John Wiley & Sons, Ltd.)

An important challenge facing the application of implanted biomaterials for tissue engineering is the need to facilitate desirable tissue interactions with the implant while simultaneously inhibiting bacterial colonization, which can lead to implant-associated infection. In this study, we explore the relevance of the physical parameters of polyelectrolyte multilayers, such as surface charge, wettability, and stiffness, in tissue cell/surface and bacteria/surface interactions, and investigate the tuning of the multilayer architecture to differentially control such interactions. Polyions with different side-chain chemical structures were paired with polyethylenimine to assemble multilayers with parallel control over surface charge and wettability under controlled conditions. The multilayers can be successfully cross-linked to yield stiffer (the apparent Young's modulus was increased more than three times its original value) and more stable films while maintaining parallel control over surface charge and wettability. The initial adhesion and proliferation of 3T3 fibroblast cells were found to be strongly affected by surface charge and wettability on the non-cross-linked multilayers. On the other hand, these cells adhered and proliferated in a manner similar to those on the cross-linked multilayers (apparent Young's modulus ∼2 MPa), regardless of surface charge and wettability. In contrast, Staphylococcus aureus ( S. aureus) and Escherichia coli ( E. coli) adhesion was primarily controlled by surface charge and wettability on both cross-linked and non-cross-linked multilayers. In both cases, negative charge and hydrophilicity inhibited their adhesion. Thus, a surface coating with a relatively high degree of stiffness from covalent cross-linking coupled with negative surface charge and high wettability can serve as an efficient strategy to enhance host cell growth while resisting bacterial colonization.

Understanding protein adsorption behaviors on solid surfaces constitutes an important step toward development of efficacious and biocompatible medical devices. Both surface charge and wettability have been shown to influence protein adsorption attributes, including kinetics, quantities, deformation, and reversibility. However, determining the dominant interaction in these surface-induced phenomena is challenging because of the complexity of inter-related mechanisms at the liquid/solid interface. Herein, we reveal the dominant interfacial forces in these essential protein adsorption attributes under the influence of a combination of surface charge and wettability, using quartz crystal microbalance with dissipation monitoring and atomic force microscopy-based force spectroscopy on a series of model surfaces. These surfaces were fabricated via layer-by-layer assembly, which allowed two-dimensional control of surface charge and wettability with minimal cross-parameter dependency. We focused on a soft globular protein, bovine serum albumin (BSA), which is prone to conformational changes during adsorption. The information obtained from the two techniques shows that both surface charge and hydrophobicity can increase the protein-surface interaction forces and the adsorbed amount. However, surface hydrophobicity triggered a greater extent of deformation in the adsorbed BSA molecules, leading to more dehydration, spreading, and resistance to elution by ionic strength changes regardless of the surface charge. The role played by the surface charge in the adsorbed protein conformation and extent of desorption induced by changes in the ionic strength is secondary to that of surface hydrophobicity. These findings advance the understanding of how surface chemistry and properties can be tailored for directing protein-substrate interactions.

It is highly desirable to develop new and more potent biocompatible antimicrobial agents to reduce the increasing risk of bacterial infection worldwide. To address this problem, we prepared a smart pH-sensitive polymer, poly( N '-citraconyl-2-(3-aminopropyl- N , N -dimethylammonium)ethyl methacrylate), or P(CitAPDMAEMA), which can undergo change in functionality from a biocompatible zwitterionic polymer to an antimicrobial cationic polymer at acidic bacterial infection sites. The precursor polymer, poly(2-(3-aminopropyl- N , N -dimethylammonium)ethyl methacrylate) (P(APDMAEMA)), was first prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization, and then modified with citraconic anhydride to obtain the zwitterionic P(CitAPDMAEMA). P(CitAPDMAEMA) is zwitterionic at physiological pH and exhibits low hemotoxicity and good biocompatibility. However, P(CitAPDMAEMA) can change from neutral to cationic with decreasing pH because of the hydrolysis of citraconic amide under low pH conditions. This switch leads to pronounced bacteria binding of cationic P(CitAPDMAEMA) under acidic conditions of the infection sites and significantly inhibits the growth of Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). These results indicate that P(CitAPDMAEMA) is potentially a new on-demand antimicrobial agent.

Bacteria-contaminated inanimate surfaces within hospitals and clinics result in transmission of pathogens via direct or indirect contact, leading to increased risk of healthcare-associated infections (HAI). The use of antibacterial coatings is a potential way of reducing the bacterial burden, but many surfaces such as instrument panels and monitors necessitate the coatings to be transparent while being highly antibacterial. In this work, silica nanoparticles (SiO 2 NPs) were first grown over a layer of acrylated quaternized chitosan (AQCS) covalently immobilized on commercially available transparent poly(vinyl fluoride) (PVF) films. The SiO 2 NPs then served as nanoreservoirs for adsorption of copper ions. The coated PVF films were transparent and reduced viable bacterial count by ∼99% and 100%, when incubated with a bacteria-loaded droplet for 60 and 120 min, respectively. The killing efficacy of these coatings, after wiping 100 times, with a deionized water-wetted cloth was reduced slightly to 97-98%. The stability of these coatings can be further improved with the deposition of another layer of cationic quaternized chitosan (QCS) over the negatively charged SiO 2 NP layer, wherein the coatings maintained ∼99% killing efficacy even after 100 wipes. These coatings showed no significant toxicity to mammalian cells and, hence, can potentially be used in a clinical setting for reducing HAI.

Biomimetic poly(catecholamine) coatings have gained much attention in recent years due to their versatility as functional materials. Despite this, only limited methods are available to modify the function and property of poly(catecholamine) coatings, primarily through post-modification methods. Our approach reported herein provides a simple approach to the fabrication of novel functionalized poly(catecholamine) coatings. The strategy employs the copolymerization of N-Ac-3,4-dihydroxyphenylalanine methyl ester (NADOPAMe) with nucleophilic additives, giving rise to nano-coatings on various surfaces including plastic, metal, glass and polymers. With the appropriate choice of nucleophilic additives, coatings with desired properties can be achieved. This is demonstrated through the fabrication of a redox responsive coating based on NADOPAMe with cysteamine as additive, which shows a concentration-dependent glutathione (GSH) responsive behavior. The ability to utilize this as a controlled release system is also demonstrated.

Arginine polymer based coatings with switchable properties were developed on glass slides (GS) to demonstrate the smart transition from antimicrobial (cationic) to fouling-resistant (zwitterionic) surfaces. l-Arginine methyl ester-methacryloylamide (Arg-Est) and l-arginine-methacryloylamide (Arg-Me) polymer brushes were grafted from the GS surface via surface-initiated reversible addition-fragmentation chain-transfer (SI-RAFT) polymerization. In comparison to the pristine GS and Arg-Me graft polymerized GS (GS-Arg-Me) surfaces, the Arg-Est polymer brushes-functionalized GS surfaces exhibit a superior antimicrobial activity. Upon hydrolysis treatment, the strong bactericidal efficacy switches to good resistance to adsorption of bovine serum albumin (BSA), the adhesion of Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli, as well as the attachment of Amphora coffeaeformis. In addition, the switchable coatings are proven to be biocompatible. The stability and durability of the switchable coatings are also ascertained after exposure to filtered seawater for 30 days. Therefore, deposition of the proposed "smart coatings" offers another environmentally friendly alternative for combating biofouling.

Indwelling medical devices such as catheters are a ubiquitous and indispensable component in modern medical practice for improving therapeutic outcomes for patients. Yet at the same time, they can be a cause of healthcare-associated infections contributing to patient morbidity and mortality, and healthcare costs. Other surface-related complications can also arise from interactions of the catheter with biological components in the in vivo environment. This review summarizes the progress made in the development of antimicrobial surfaces, and the application of surface modification strategies to three important classes of catheters: urinary catheters, intravascular catheters and peritoneal dialysis catheters. The review also provides a perspective on the challenges in translating favorable developments from in vitro studies into similar clinical outcomes.

Immobilization of alendronate on orthopedic implants offers the possibility of enhancing osteogenesis without potentially adverse effects associated with systemic administration of this drug. In this work, alendronate was immobilized on titanium (Ti) via either its phosphate (Method 1) or amino (Method 2) groups, and responses of osteoblasts and human mesenchymal stem cells (hMSCs) on these surfaces were investigated. These modified substrates have similar surface roughness and are negatively charged. With similar amounts of immobilized alendronate, these two types of modified substrates showed comparable osteogenic stimulating effects in enhancing osteoblasts' alkaline phosphatase (ALP) activity and calcium deposition for the first 10days. However, alendronate immobilized via its phosphate groups was less stable, and gradually leached into the medium. As a result, its stimulating effect on osteoblast differentiation diminished with time. On the other hand, alendronate immobilized via its amino group stimulated osteoblast differentiation over 21days, and with 1655ng/cm 2 of immobilized alendronate on the Ti substrate, calcium deposition by osteoblasts and hMSCs increased by 30% and 69%, respectively, compared to pristine Ti after 21days. The expressions of runt-related transcription factor 2, osterix, osteopontin and osteocalcin in hMSCs cultured on this substrate were monitored. The up-regulation of these genes is postulated to play a role in the acceleration of osteogenic differentiation of hMSCs cultured on the alendronate-modified substrate over those on pristine Ti., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bacterial contamination of surfaces and the associated infection risk is a significant threat to human health. Some natural antibacterial polymers with low toxicity are promising coating materials for alleviating pathogenic colonization on surfaces. However, widespread application of these polymers as antibacterial coatings is constrained by coating techniques which are not easily scalable due to stringent reaction conditions. Herein, thiol-ol reaction involving oxidative conjugation between thiol and hydroxyl groups is demonstrated as a facile technique to graft two natural polymer derivatives, agarose (AG) and quaternized chitosan (QCS), as antibacterial coatings on polymer and metal substrates. The substrate surfaces are first treated with oxygen plasma followed by UV-induced grafting of the polymers under atmospheric conditions. Dimercaprol, a FDA-approved drug, is used as both surface anchor and cross-linker of the polymer chains during grafting. The AG coating achieves >2 log reduction in Pseudomonas aeruginosa and Staphylococcus aureus biofilm formation, while the QCS coating reduces bacterial count from contaminated droplets on its surface by >95%. The coatings are noncytotoxic and exhibits a high degree of stability under conditions expected in their potential applications as antibacterial coating for biomedical devices (for AG), and for preventing pathogen transmission in the environment (for QCS).

In this work, carbon black waste - a hazardous solid residue generated from gasification of crude oil bottom in refineries - was successfully used for making an absorbent material. However, since the carbon black waste also contains significant amounts of heavy metals (especially nickel and vanadium), chemical leaching was first used to remove these hazardous impurities from the carbon black waste. Acid leaching with nitric acid was found to be a very effective method for removal of both nickel and vanadium from the carbon black waste (i.e. up to 95% nickel and 98% vanadium were removed via treatment with 2M nitric acid for 1h at 20°C), whereas alkali leaching by using NaOH under the same condition was not effective for removal of nickel (less than 10% nickel was removed). Human lung cells (MRC-5) were then used to investigate the toxicity of the carbon black waste before and after leaching. Cell viability analysis showed that the leachate from the original carbon black waste has very high toxicity, whereas the leachate from the treated samples has no significant toxicity. Finally, the efficacy of the carbon black waste treated with HNO 3 as an absorbent for dye removal was investigated. This treated carbon black waste has high adsorption capacity (∼361.2mg dye /g carbonblack ), which can be attributed to its high specific surface area (∼559m 2 /g). The treated carbon black waste with its high adsorption capacity and lack of cytotoxicity is a promising adsorbent material. Moreover, the carbon black waste was found to show high electrical conductivity (ca. 10S/cm), making it a potentially valuable source of conductive material., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In Singapore, approximately 30t/day of carbon-based solid waste are produced from petrochemical processes. This carbon black waste has been shown to possess physical properties that are characteristic of a good adsorbent such as high external surface area. Therefore, there is a growing interest to reutilize and process this carbon black waste into secondary materials such as adsorbents. However, the carbon black waste obtained from petrochemical industries may contain heavy metals that are hazardous to human health and the environment, hence restricting its full potential for re-utilization. Therefore, it is important to examine the possible toxicity effects and toxicity mechanism of carbon black waste on human health. In this study, inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis showed that the heavy metals, vanadium (V), molybdenum (Mo) and nickel (Ni), were present in the carbon black waste in high concentrations. Three human cell lines (HepG2 cells, MRC-5 cells and MDA-MB-231 cells) were used to investigate the toxicity of carbon black waste extract in a variety of in vitro assays. Results from MTS assays indicated that carbon black waste extract decreased the viability of all three cell lines in a dose and time-dependent manner. Observations from confocal microscopy further confirmed this phenomenon. Flow cytometry assay also showed that carbon black waste extract induced apoptosis of human cell lines, and the level of apoptosis increased with increasing waste concentration. Results from reactive oxygen species (ROS) assay indicated that carbon black waste extract induced oxidative stress by increasing intracellular ROS generation in these three human cell lines. Moreover, induction of oxidative damage in these cells was also observed through the alteration of glutathione (GSH) and superoxide dismutase (SOD) activities. Last but not least, by treating the cells with V-spiked solution of concentration equivalent to that found in the carbon black waste extract, V was identified as the main culprit for the high toxicity of carbon black waste extract. These findings could potentially provide insight into the hazards of carbon black waste extract and its toxicity mechanism on human cell lines., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Dopamine (DA) protected by an o-nitrobenzyl functionality on its phenolic group was synthesized as a photolabile catecholamine derivative. This compound, o-nitrobenzyl dopamine (NBDA), was more stable than DA in basic solution at pH 8.5 and will not self-polymerize when protected from light. UV irradiation of a methanolic solution of NBDA at 365 nm for 40 min induced ca. 85% deprotection. Taking advantage of the stability of NBDA, a one-pot spray coating technique for modifying surfaces with polydopamine (PDA) was developed. Using ethylene glycol with Tris buffer (pH 8.5) as the solvent for this technique, stainless steel substrates can be coated with a robust PDA layer. Silver was deposited on the PDA-coated surface after treatment with silver nitrate solution, and >80% of the deposited silver remained on the surface after 1 week immersion in water. The NBDA-Ag surface was highly effective in inhibiting Staphylococcus aureus (S. aureus) biofilm formation.

Surface charge and wettability, the two prominent physical factors governing protein adsorption and cell adhesion, have been extensively investigated in the literature. However, a comparison between these driving forces in terms of their independent and cooperative effects in affecting adhesion is rarely explored on a systematic and quantitative level. Herein, we formulate a protocol that features two-dimensional control over both surface charge and wettability with limited cross-parameter influence. This strategy is implemented by controlling both the polyion charge density in the layer-by-layer (LbL) assembly process and the polyion side-chain chemical structures. The 2D property matrix spans surface isoelectric points ranging from 5 to 9 and water contact angles from 35 to 70°, with other interferential factors (e.g., roughness) eliminated. The interplay between these two surface variables influences protein (bovine serum albumin, lysozyme) adsorption and 3T3 fibroblast cell adhesion. For proteins, we observe the presence of thresholds for surface wettability and electrostatic driving forces necessary to affect adhesion. Beyond these thresholds, the individual effects of electrostatic forces and wettability are observed. For fibroblast, both surface charge and wettability have an effect on its adhesion. The combined effects of positive charge and hydrophilicity lead to the highest cell adhesion, whereas negative charge and hydrophobicity lead to the lowest cell adhesion. Our design strategy can potentially form the basis for studying the distinct behaviors of electrostatic force or wettability driven interfacial phenomena and serve as a reference in future studies assessing protein adsorption and cell adhesion to surfaces with known charge and wettability within the property range studied here.

Tuberculosis (TB) is still a serious public health problem in various countries. One of the long-elusive but critical questions about TB is what the risk factors are and how they contribute for its seasonality. An ecologic study was conducted to examine the association between the variation of outdoor PM 2.5 concentration and the TB seasonality based on the monthly TB notification and PM 2.5 concentration data of Hong Kong and Beijing. Both descriptive analysis and Poisson regression analysis suggested that the outdoor PM 2.5 concentration could be a potential risk factor for the seasonality of TB disease. The significant relationship between the number of TB cases and PM 2.5 concentration was not changed when regression models were adjusted by sunshine duration, a potential confounder. The regression analysis showed that a 10 μg/m 3 increase in PM 2.5 concentrations during winter is significantly associated with a 3% (i.e. 18 and 14 cases for Beijing and Hong Kong, respectively) increase in the number of TB cases notified during the coming spring or summer for both Beijing and Hong Kong. Three potential mechanisms were proposed to explain the significant relationship: (1) increased PM 2.5 exposure increases host's susceptibility to TB disease by impairing or modifying the immunology of the human respiratory system; (2) increased indoor activities during high outdoor PM 2.5 episodes leads to an increase in human contact and thus the risk of TB transmission; (3) the seasonal change of PM 2.5 concentration is correlated with the variation of other potential risk factors of TB seasonality. Preliminary evidence from the analysis of this work favors the first mechanism about the PM 2.5 exposure-induced immunity impairment. This work adds new horizons to the explanation of the TB seasonality and improves our understanding of the potential mechanisms affecting TB incidence, which benefits the prevention and control of TB disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated., Methods: Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria., Results: Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria., Conclusions: These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.

Coatings based on thin films of agarose-poly(ethylene glycol) (Agr-PEG) cross-linked systems are developed as environmentally-friendly and fouling-resistant marine coatings. The Agr-PEG cross-linked systems were prepared via thermal azide-alkyne cycloaddition (AAC) using azido-functionalized Agr (AgrAz) and activated alkynyl-containing poly(2-propiolamidoethyl methacrylate-co-poly(ethylene glycol)methyl ether methacrylate) P(PEMA-co-PEGMEMA) random copolymers as the precursors. The Agr-PEG cross-linked systems were further deposited onto a SS surface, pre-functionalized with an alkynyl-containing biomimetic anchor, dopamine propiolamide, to form a thin film after thermal treatment. The thin film-coated SS surfaces can effectively reduce the adhesion of marine algae and the settlement of barnacle cyprids. Upon covalent cross-linking, the covalently cross-linked Agr-PEG films coated SS surfaces exhibit good stability in flowing artificial seawater, and enhanced resistance to the settlement of barnacle cyprids, in comparison to that of the surfaces coated with physically cross-linked AgrAz films., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The solid residues including bottom ashes and fly ashes produced by waste gasification technology could be reused as secondary raw materials. However, the applications and utilizations of these ashes are very often restricted by their toxicity. Therefore, toxicity screening of ash is the primary condition for reusing the ash. In this manuscript, we establish a standard for rapid screening of gasification ashes on the basis of in vitro and in vivo testing, and henceforth guide the proper disposal of the ashes. We used three different test models comprising human cell lines (liver and lung cells), Drosophila melanogaster and Daphnia magna to examine the toxicity of six different types of ashes. For each ash, different leachate concentrations were used to examine the toxicity, with C0 being the original extracted leachate concentration, while C/C0 being subsequent diluted concentrations. The IC50 for each leachate was also quantified for use as an index to classify toxicity levels. The results demonstrated that the toxicity evaluation of different types of ashes using different models is consistent with each other. As the different models show consistent qualitative results, we chose one or two of the models (liver cells or lung cells models) as the standard for rapid toxicity screening of gasification ashes. We may classify the gasification ashes into three categories according to the IC50, 24h value on liver cells or lung cells models, namely "toxic level I" (IC50, 24h>C/C0=0.5), "toxic level II" (C/C0=0.05

Synergistic effect against UMUC3 bladder cancer cells was demonstrated via a "two-in-one" combination of doxorubicin (Dox) and peptide-modified cisplatin (Pt-ALy) loaded in positively charged mucoadhesive chitosan-polymethacrylic acid (CM) nanocapsules. The in vitro killing efficacy of the dual drug-loaded nanocapsules (CM-Dox-PtALy) against UMUC3 cells after 4h- and 72h-treatment is much higher (with 5-16 times lower IC50) than either Dox- or Pt-ALy-loaded nanocapsules, resulting in combination indexes of much less than 1 (i.e. obvious synergism) at fractions of affected cells ranging from 0.2 to 0.8. The dose reduction index of Pt-ALy for 72h-treatment is higher than for 4h-treatment, suggesting that Dox in CM-Dox-PtALy played a more significant role in the synergy in the former. The drug-loaded CM nanocapsules are readily taken in by the cells as shown by flow cytometry, confocal laser scanning microscopy and inductively coupled plasma mass spectrometry. Microscopy observations indicate that CM nanocapsules attach strongly on the luminal surface of the bladder with no obvious damage of the urothelium, supporting our objective of prolonging the dwell time of the drug-loaded nanocapsules for intravesical applications. Our study indicates that the mucoadhesive CM-Dox-PtALy nanocapsules have a high drug loading and a sustained release profile, and thus, are promising for synergistic intravesical chemotherapy of non-muscle-invasive bladder cancers., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Since electrical stimulation (ES) can significantly accelerate bone healing, a conductive scaffold that can deliver ES locally at the defect site is desirable for bone defect therapy. Herein, an electrically conductive scaffold was prepared via incorporation of polypyrrole (PPY) in a polycaprolactone (PCL) template scaffold. In vitro tests with mouse osteoblasts indicate that the PPY/PCL scaffold has good biocompatibility, and is suitable for use as an ES substrate. When human adipose-derived mesenchymal stem cells (AD-MSCs) were cultured in the PPY/PCL scaffold and subjected to 200 μA of direct current for 4h per day for 21 days, the amount of calcium deposited was 100% higher than that without ES. When these cells were subjected to ES together with blockers of voltage-gated calcium (Ca(2+)v), sodium (Na(+)v), potassium (K(+)v), or chloride (Cl(-)v) channels, the ES-induced enhancement of AD-MSCs' functions was reduced with Na(+)v, K(+)v, or Cl(-)v blockers and completely nullified with Ca(2+)v blocker. These results indicate that ion fluxes through these channels activated by ES induce different cascades of reactions in the cells, which subsequently regulate AD-MSCs' functions, and Ca(2+)v plays a more critical role than the other three channels. Our results further the current understanding of the mechanisms by which ES regulates stem cells' behavior, and also showed that the conductive PPY/PCL scaffold with application of ES has good potential in bone defect therapy., Statement of Significance: In this work, an electrically conductive and biocompatible scaffold was prepared by incorporating polypyrrole in a polycaprolactone template scaffold. Application of 200 μA direct current for 4h per day to human adipose derived-mesenchymal stem cells cultured on this scaffold promoted migration of these cells into the inner region of the scaffold and enhanced their osteogenic differentiation. The roles of voltage-gated ion channels (Ca(2+)v, Na(+)v, K(+)v and Cl(-)v) in osteogenic differentiation stimulated by the electric current were investigated. The results from these experiments further the current understanding of the mechanisms by which electrical stimulation regulates stem cells' behavior, and also show that the polypyrrole-polycaprolactone scaffold with application of electrical stimulation has good potential in bone defect therapy., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hypothesis: Electrostatic interactions play an important role in adhesion phenomena particularly for biomacromolecules and microorganisms. Zero charge valence of zwitterions has been claimed as the key to their antifouling properties. However, due to the differences in the relative strength of their acid and base components, zwitterionic materials may not be charge neutral in aqueous environments. Thus, their charge on surfaces should be further adjusted for a specific pH environment, e.g. physiological pH typical in biomedical applications., Experiments: Surface zeta potential for thin polymeric films composed of polysulfobetaine methacrylate (pSBMA) brushes is controlled through copolymerizing zwitterionic SBMA and cationic methacryloyloxyethyltrimethyl ammonium chloride (METAC) via surface-initiated atom transfer polymerization. Surface properties including zeta potential, roughness, free energy and thickness are measured and the antifouling performance of these surfaces is assessed., Findings: The zeta potential of pSBMA brushes is -40 mV across a broad pH range. By adding 2% METAC, the zeta potential of pSBMA can be tuned to zero at physiological pH while minimally affecting other physicochemical properties including dry brush thickness, surface free energy and surface roughness. Surfaces with zero and negative zeta potential best resist fouling by bovine serum albumin, Escherichia coli and Staphylococcus aureus. Surfaces with zero zeta potential also reduce fouling by lysozyme more effectively than surfaces with negative and positive zeta potential., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A straight forward strategy of heparin surface grafting employs a terminal reactive-aldehyde group introduced through nitrous acid depolymerization. An advanced method that allows simultaneously monitoring of both heparin molar mass and monomer/aldehyde ratio by size exclusion chromatography, multi-angle laser light scattering and UV-absorbance (SEC-MALLS-UV) has been developed to improve upon heparin surface grafting. Advancements over older methods allow quantitative characterization by direct (aldehyde absorbance) and indirect (Schiff-based absorbance) evaluation of terminal functional aldehydes. The indirect quantitation of functional aldehydes through labeling with aniline (and the formation of a Schiff-base) allows independent quantitation of both polymer mass and terminal functional groups with the applicable UV mass extinction coefficients determined. The protocol was subsequently used to synthesize an optimized heparin-aldehyde that had minimal polydispersity (PDI<2) and high reaction yields (yield >60% by mass). The 8 kDa weight averaged molar mass heparin-aldehyde was then grafted on polycaprolactone (PCL), a common implant material. This optimized heparin-aldehyde retained its antithrombin activity, assessed in freshly drawn blood or surface immobilized on PCL films. Anticoagulant activity was equal to or better than the 24 kDa unmodified heparin it was fragmented from., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Bacterial colonization by nosocomial pathogens on medical device surface can cause serious and life-threatening infections. We showed that 4-amide-piperidine-C12 (4AP12), the base form of 4-dodecaneamidepiperidine HCl, has broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria and fungi. Resistance assay confirmed that prolonged exposure of bacteria to subinhibitory concentrations of 4AP12 did not induce resistance to 4AP12. The possible antimicrobial mechanism of 4AP12 was investigated, and attributed to the disruption of the cell membrane of microorganisms and subsequent cell lysis. The hydrophobic 4AP12 was incorporated in Pluronic F127 diacrylate (F127DA) micelles, which were then graft-copolymerized with acrylic acid and cross-linked onto ozonized silicone surface. Sulfobetaine methacrylate and F127DA were then graft-copolymerized as an antifouling layer on top of the F127DA-AA hydrogel containing the 4AP12, thus forming a microscale two-layer bifunctional coating. Sustained release of 4AP12 at a rate of up to 1 μg/day per cm 2 of hydrogel-coated silicone surface was achieved and this was sufficient to inhibit ∼97% of bacterial colonization by Acinetobacter baumannii in artificial urine medium under static condition over a 14-day period. Bacterial colonization by Escherichia coli and Pseudomonas aeruginosa under similar conditions was also significantly reduced. In addition, after 96 h exposure to flowing artificial urine (0.7 mL/min), Escherichia coli colonization on the 4AP12-loaded hydrogel-coated surface was reduced by ∼89% compared to the pristine surface. The concentration of 4AP12 that was released and was effective in inhibiting bacterial colonization did not result in significant cytotoxicity to human epithelial cells.

In this paper, amine-functionalized polyacrylamide nanogels (PAm-NH2) loaded with docetaxel (DTX) were evaluated as a mucoadhesive and sustained intravesical drug delivery (IDD) system for potential bladder cancer therapy. Nanogels have not been applied for such therapy before. The mucoadhesiveness of the PAm-NH2 nanogels, which is a critical factor for IDD application, was investigated using the mucin-particle method and by analyzing the direct attachment of the PAm-NH2 nanogels onto the luminal surface of porcine urinary bladder. DTX, as a model hydrophobic drug, was successfully loaded into hydrophilic PAm-NH2 nanogels with high loading efficiency (>90%), and sustained release of DTX from the nanogels over 9 days in artificial urine was achieved. The nanogels were also taken in by bladder cancer cells in a concentration-dependent manner. The efficiency of the DTX-loaded nanogels in killing UMUC3 and T24 bladder cancer cells was determined to be equivalent to free DTX, and the morphology of the bladder urothelium was not adversely altered by the PAm-NH2 nanogels. These findings indicate that such mucoadhesive nanogels are potentially a promising candidate for intravesical delivery of hydrophobic drugs in bladder cancer therapy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Urinary tract infections constitute a large proportion of nosocomial infections, and the urinary catheter is the most important predisposing factor. Encrustation induced by urease-producing uropathogens like Proteus mirabilis causes further complications. In the present work, a strategy for controllable and sustained release of silver over several weeks has been developed for combating bacterial infection and encrustation in urinary devices. Silver nanoparticles (AgNPs) were first immobilized on polydopamine (PDA) pre-treated silicone catheter surface and this was followed by another PDA coating. The number of AgNP-PDA bilayers could be manipulated to control the amount of silver loaded and its subsequent release. Poly(sulfobetaine methacrylate-co-acrylamide) was then grafted to provide an antifouling outer layer, and to ensure free diffusion of Ag from the surface. The micron-scale combination of an antifouling coating with AgNP-PDA bilayers reduced colonization of the urinary catheter by uropathogens by approximately two orders of magnitude. With one and two AgNP-PDA bilayers, the coated catheter could resist encrustation for 12 and 45 days, respectively, compared with approximately 6 days with the Dover™ silver-coated catheter. Such anti-infective and anti-encrustation catheters can potentially have a large impact on reducing patient morbidity and healthcare expenditure., (© 2014 Wiley Periodicals, Inc.)

Inspired by tea stains, plant polyphenolic tannic acid (TA) was beneficially employed as the primer anchor for functional polymer brushes. The brominated TA (TABr) initiator primer was synthesized by partial modification of TA with alkyl bromide functionalities. TABr with trihydroxyphenyl moieties can readily anchor on a wide range of substrates, including metal, metal oxide, polymer, glass, and silicon. Concomitantly, the alkyl bromide terminals serve as initiation sites for atom transfer radical polymerization (ATRP). Cationic [2-(methacryloyloxy)ethyl]trimethylammonium chloride (META) and zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and N-(3-sulfopropyl)-N-(methacryloxyethyl)-N,N-dimethylammonium betaine (SBMA) were graft-polymerized from the TABr-anchored stainless steel (SS) surface. The cationic polymer brushes on the modified surfaces are bactericidal, while the zwitterionic coatings exhibit resistance against bacterial adhesion. In addition, microalgal attachment (microfouling) and barnacle cyprid settlement (macrofouling) on the functional polymer-grafted surfaces were significantly reduced, in comparison to the pristine SS surface. Thus, the bifunctional TABr initiator primer provides a unique surface anchor for the preparation of functional polymer brushes for inhibiting both microfouling and macrofouling.

As the demand for fossil fuels and biofuels increases, the volume of ash generated will correspondingly increase. Even though ash disposal is now strictly regulated in many countries, the increasing volume of ash puts pressure on landfill sites with regard to cost, capacity and maintenance. In addition, the probability of environmental pollution from leakage of bottom ash leachate also increases. The main aim of this research is to investigate the toxicity of bottom ash, which is an unavoidable solid residue arising from biomass gasification, on human cells in vitro. Two human cell lines i.e. HepG2 (liver cell) and MRC-5 (lung fibroblast) were used to study the toxicity of the bottom ash as the toxins in the bottom ash may enter blood circulation by drinking the contaminated water or eating the food grown in bottom ash-contaminated water/soil and the toxic compounds may be carried all over the human body including to important organs such as lung, liver, kidney, and heart. It was found that the bottom ash extract has a high basicity (pH = 9.8-12.2) and a high ionic strength, due to the presence of alkali and alkaline earth metals e.g. K, Na, Ca and Mg. Moreover, it also contains concentrations of heavy metals (e.g. Zn, Co, Cu, Fe, Mn, Ni and Mo) and non-toxic organic compounds. Although human beings require these trace elements, excessive levels can be damaging to the body. From the analyses of cell viability (using MTS assay) and morphology (using fluorescence microscope), the high toxicity of the gasification bottom ash extract could be related to effects of high ionic strength, heavy metals or a combination of these two effects. Therefore, our results suggest that the improper disposal of the bottom ash wastes arising from gasification can create potential risks to human health and, thus, it has become a matter of urgency to find alternative options for the disposal of bottom ash wastes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Hypothesis: Surface coatings that are either antifouling or bactericidal can reduce bacterial colonization, but either type has certain drawbacks. We hypothesize that by integrating an antifouling polymer, poly(sulfobetaine methacrylate) (pSBMA), and a bactericidal polymer, N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride (HTCC), in one coating, these drawbacks can be overcome and the antibacterial efficacy can be greatly improved compared to an antifouling or bactericidal coating., Experiments: A copolymer comprising chitosan and pSBMA in almost equal molar ratio was grafted onto an aminolyzed silicone surface via genipin-induced crosslinking reaction, and treated with glycidyltrimethylammonium chloride to endow the surface with quaternary ammonium groups. The antibacterial property and cytotoxicity of the resultant coating (HTCC-b-pSBMA) were tested. The possibility of incorporating heparin in the coating to improve blood compatibility was also investigated., Findings: The HTCC-b-pSBMA coating reduced colonization by both planktonic bacteria from aqueous medium and aerosolized bacteria by approximately two orders of magnitude compared with the pristine surface. In comparison, surfaces coated with either the pSBMA or HTCC component are unable to achieve such efficacy. The heparin-loaded HTCC-b-pSBMA coating improved hemocompatibility without adversely affecting the antibacterial efficacy. No significant cytotoxicity of the coatings was observed with mammalian cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Treatment of biofilm-related infections in orthopedics remains a serious clinical challenge. It is known that an electric current can significantly enhance the potency of some antibiotics against biofilms (bioelectric effect) but the uncertainty of the mechanisms and the electrolytic cell-like system used in previous studies limit its applications. Herein, the behavior of Staphylococcus aureus (S. aureus) on an electrically conductive polypyrrole/chitosan film upon passage of a direct current (DC) through the film was investigated in the absence and presence of gentamicin. The killing efficacy of the bacteria within the biofilm by gentamicin was greatly enhanced by the DC treatment. From an analysis of the gene expression by the biofilm bacteria after treatment with gentamicin, DC and their combination, it is postulated that the promotion of bacterial autolysis by DC treatment is responsible for the enhanced susceptibility of biofilm S. aureus to gentamicin. This postulate is supported by an increase in the amount of extracellular deoxyribonucleic acid and adenosine triphosphate, and the appearance of disrupted bacterial cells in the biofilm after DC treatment. These findings provide a new insight into the interaction between DC and bacteria, and offer potential benefits for the treatment of infections in orthopedics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The synthesis of a series of β-cyclodextrin modified mesoporous silica nanoparticles with hydroxyl, amino, and thiol groups was described. A comparison of their mucoadhesive properties and potential as a drug delivery system for superficial bladder cancer therapy was made. The thiol-functionalized nanoparticles exhibit significantly higher mucoadhesivity on the urothelium as compared to the hydroxyl- and amino-functionalized nanoparticles. This is attributed to the formation of disulfide bonds between the thiol-functionalized nanoparticles and cysteine-rich subdomains of mucus glycoproteins. An anticancer drug, doxorubicin, was loaded into the mesopores of the thiol-functionalized nanoparticles, and sustained drug release triggered by acidic pH was achieved. The present study demonstrates that thiol-functionalized mesoporous silica nanoparticles are promising as a mucoadhesive and sustained drug delivery system for superficial bladder cancer therapy.

A versatile template-assisted strategy for the preparation of monodispersed rattle-type hybrid nanospheres, encapsulating a movable Au nanocore in the hollow cavity of a hairy electroactive polymer shell (Au@air@PTEMA-g-P3HT hybrid nanorattles; PTEMA: poly(2-(thiophen-3-yl)ethyl methacrylate; P3HT: poly(3-hexylthiophene), was reported. The Au@silica core-shell nanoparticles, prepared by the modified Stöber sol-gel process on Au nanoparticle seeds, were used as templates for the synthesis of Au@silica@PTEMA core-double shell nanospheres. Subsequent oxidative graft polymerization of 3-hexylthiophene from the exterior surface of the Au@silica@PTEMA core-double shell nanospheres allowed the tailoring of surface functionality with electroactive P3HT brushes (Au@silica@PTEMA-g-P3HT nanospheres). The Au@air@ PTEMA-g-P3HT hybrid nanorattles were obtained after etching of the silica interlayer by HF. The as-prepared nanorattles were dispersed into an electrically insulating polystyrene matrix and for the first time used to fabricate nonvolatile memory devices. As a result, unique electrical behaviors, including insulator behavior, write-once-read-many-times and rewritable memory effects, and conductor behavior as well, were observed in the Al/Au@air@PTEMA-g-P3HT+PS/ITO (ITO: indium-tin oxide) sandwich thin-film devices., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypothesis: Anatase-modified titanium (Ti) substrates have been found to possess antibacterial properties in the absence of ultraviolet irradiation, but the mechanism is not known. We hypothesize that this is due to the bactericidal effects of reactive oxygen species (ROS) generated by the surface anatase., Experiments: Alkali and heat treatment was used to form anatase on Ti surface. The generation of ROS, and the behavior of bacteria and osteoblasts on the anatase-modified Ti were investigated. Cobalt-chrome (Co-Cr) alloys and stainless steel (SS) were similarly treated with alkali and heat, and their surface properties and effects on bacteria and osteoblasts were compared with the results obtained with Ti., Findings: The anatase-functionalized Ti substrates demonstrated significant bactericidal effects and promoted apoptosis in osteoblasts, likely a result of ROS generated by the anatase. The alkali and heat-treated Co-Cr and SS substrates also reduced bacterial adhesion but were not bactericidal. This effect is likely due to an increase in hydrophilicity of the surfaces, and no significant ROS were generated by the alkali and heat-treated Co-Cr and SS substrates. The treated Co-Cr and SS substrates did not induce significant apoptosis in osteoblasts, and thus with these properties, they may be promising for orthopedic applications., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Hyperbranched poly(ε-caprolactone) with peripheral terminal alkyne groups (HPCL) was synthesized via thiol-yne click reaction among the AB 2 -type α-thiol-ω-alkyne-poly(ε-caprolactone) (CH[triple bond, length as m-dash]C-PCL-SH) linear precursors. Azide-terminated poly(N-vinylcaprolactam) (PVCL-N 3 ), prepared a priori via xanthate-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization of N-vinylcaprolactam (VCL), was then linked to HPCL chains through Cu(i)-catalyzed alkyne-azide click reaction. The resultant hyperbranched-linear HPCL-click-PVCL copolymers were cast, by phase inversion in an aqueous medium, into microporous membranes of well-defined and uniform pores. The PVCL content in the HPCL-click-PVCL copolymers could be used to control the pore size and porosity of the resulting membranes. The temperature-responsive characteristics of the HPCL-click-PVCL membranes were illustrated in the swelling behavior and controlled drug transport through the membranes. These stimuli responsive membranes with controllable morphology, improved mechanical properties and negligible cytotoxicity are useful as biomaterials for controlled drug delivery.

An integrated approach is proposed to incorporate silicon and silver into hydroxyapatite (HA) to enhance the biological response and reduce implant-related infection in bone substitutes. This study examined the responses of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacteria to silver, silicon-containing apatite (Ag,Si-HA). Scanning electron microscopy images revealed significant reduction in adherence of S. aureus and E. coli bacteria on Ag,Si-HA as compared to HA. The antibacterial property of Ag,Si-HA was shown from a 7-log reduction of S. aureus population in the test solution and on the sample's surface as compared to HA at day 7. Rapid inhibition of the adherent bacteria suggested that the antibacterial action of Ag incorporated in Ag,Si-HA could be attributed to the Ag(+) ions on the crystal surface rather than the released Ag(+) ions. Presence of Ag may influence the biological response of HA and as such, the long-term interaction between human adipose-derived mesenchymal stem cells and Ag,Si-HA was evaluated in-vitro. An alamarBlue™ assay showed higher cell proliferation for Ag,Si-HA as compared to HA from day 3 onwards. Immunofluorescence staining revealed well-spread actin cytoskeletons on Ag,Si-HA. In addition, signs of extracellular matrix secretion and biomineralization were observed on Ag,Si-HA at day 14 onwards. Results demonstrated enhanced bone differentiation on Ag,Si-HA, as indicated by a higher level of protein expressions (type 1 collagen and osteocalcin) from day 14 to 21. Therefore, the incorporation of Ag and Si complement each other by endowing HA with antibacterial property, and concurrently promoting biological performance of the cells.

Poly[3-azido-2-(2-bromo-2-methylpropanoyloxy)propyl methacrylate] (PAzBrMA) was synthesized as the macroinitiator and anchor for a functional polymer brush coating on polyurethane (PU) films. Ring-opening reaction of the epoxide group of poly(glycidyl methacrylate) with sodium azide produced the hydroxyl and azide functional groups. The hydroxyl groups were substituted with 2-bromoisobutyryl bromide to introduce the alkyl halide initiator. For anchoring, ultraviolet irradiation was applied to convert the azide groups of PAzBrMA physically coated on the PU surface into nitrene intermediates. The nitrene groups reacted with hydrocarbon moieties on the PU surface through hydrogen abstraction to form amine linkages. A photomask could then be employed to create a patterned surface during irradiation. Thus, the anchoring of a PAzBrMA macroinitiator can be achieved under mild conditions, without the use of strong solvents and high temperatures, which will swell or degrade the PU substrates. Finally, 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methacrylate (PEGMA) are graft-polymerized on the PAzBrMA-anchored PU film by surface-initiated atom transfer radical polymerization. In comparison with the pristine PU surface, the PU surfaces with grafted HEMA and PEGMA brush coatings were effective in reducing bovine serum albumin adsorption (protein fouling), adhesion of Staphylococcus epidermidis and Pseudomonas sp. (microfouling), and barnacle cyprid settlement (macrofouling). The present surface modification approach provides a simple and versatile means for micropatterning and functionalization of the polymer surfaces.

Thermo-responsive poly(N-isopropylacrylamide) (PIPAAm) with a particular lower critical solution temperature (LCST) have been applied for the non-invasive harvesting of confluent cell layer. Until now, the effect of adhesive ligand on the biophysical responses of cells during cell layer harvesting from PIPAAm has not been elucidated. In this study, the deadhesion kinetics of smooth muscle cells (SMC) on various adhesive ligands immobilized on PIPAAm were investigated. Firstly, the formation of elastin (EL), laminin (LA), hyaluronic acid (HA) and collagen (CL) coating on PIPAAm surfaces were validated with XPS, microBCA assay and AFM. It was shown that EL was most effective in driving cell retraction on PIPAAm surface. Moreover, the highest rate of initial SMC deadhesion on EL-PIPAAm was driven by the formation of stress fibers. Interestingly, HA was most effective in preventing initial SMC detachment from PIPAAm surface in comparison with EL, LA and CL. Also, the adhesion energy of SMC on HA-PIPAAm remained constant, which was two times and six times higher than that on CL-PIPAAm and EL-PIPAAm, respectively from 20 min onward. Overall, the results reported herein pave the way for the engineering of the invasive regeneration/recovery of cells/tissue with adhesive ligand.