Evidence-Based Review of Antibiofilm Agents for Wound Care.

Significance: Biofilms in vivo are small densely packed aggregations of microbes that are highly resistant to host immune responses and treatment. They attach to each other and to nearby surfaces. Biofilms are difficult to study and identify in a clinical setting as their quantification necessitates the use of advanced microscopy techniques such as confocal laser scanning microscopy. Nonetheless, it is likely that biofilms contribute to the pathophysiology of chronic skin wounds. Reducing, removing, or preventing biofilms is thus a logical approach to help clinicians heal chronic wounds. Recent Advances: Wound care products have demonstrated varying degrees of efficacy in destroying biofilms in in vitro and preclinical models, as well as in some clinical studies. Critical Issues: Controlled studies exploring the beneficial role of biofilm eradication and its relationship to healing in patients with chronic wounds are limited. This review aims to discuss the mode of action and clinical significance of currently available antibiofilm products, including surfactants, dressings, and others, with a focus on levels of evidence for efficacy in disrupting biofilms and ability to improve wound healing outcomes. Future Directions: Few available products have good evidence to support antibiofilm activity and wound healing benefits. Novel therapeutic strategies are on the horizon. More high-quality clinical studies are needed. The development of noninvasive techniques to quantify biofilms will facilitate increased ease of research about biofilms in wounds and how to combat them.

Effect of smear layer deproteinizing on resin-dentine interface with self-etch adhesive.

OBJECTIVES: This study aimed to investigate deproteinizing effect of sodium-hypochlorite (NaOCl) and mild acidic hypochlorous-acid (HOCl) pretreatment on smear layer-covered dentine and to evaluate their effects on morphological characteristics of resin-dentine interface with self-etch adhesive. METHODS: Human coronal-dentine discs with standardized smear layer were pretreated with 6% NaOCl or 50ppm HOCl for 15s or 30s. Their deproteinizing effects at the treated smear layer-covered dentine surfaces were determined by the measurement of amide:phosphate ratio using ATR-FTIR analysis. In addition, using TEM, micromorphological alterations of hybridized complex and nanoleakage expression were evaluated at the interface of a self-etch adhesive (Clearfil SE Bond) to the pretreated dentine surface with or without subsequent application of a reducing agent (p-Toluenesulfinic acid salt; Accel(®)). RESULTS: Both pretreatments of NaOCl and HOCl significantly reduced the amide:phosphate ratio as compared with the no-pretreated group (p<0.05), coincident with the elimination of the hybridized smear layer on their bonded interfaces. Nanoleakage within the hybrid layer was found in the no-pretreated and NaOCl-pretreated groups, whereas the subsequent reducing agent application changed the reticular nanoleakage to spotted type. HOCl-pretreated groups showed less nanoleakage expression in a spotted pattern, regardless of reducing agent application. CONCLUSIONS: NaOCl and HOCl solutions could remove the organic component on the smear layer-covered dentine, which could eliminate the hybridized smear layer created by self-etch adhesive, leading to the reduction of nanoleakage expression within hybrid layer. CLINICAL SIGNIFICANCE: Smear layer deproteinizing could modify dentine surface, giving an appropriate substrate for bonding to self-etch adhesive system.

Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice.

Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB-dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB-driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB-dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB-mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.

Evaluation of an automated dental unit water system's contamination control protocol.

BACKGROUND: This study addresses the efficacy of an automated decontamination protocol using the germicide 'tetra acetyl ethylene diamine (TAED) perborate' (Farmec SpA, Italy). The germicide TAED perborate protocol is used in the Castellini Dental Units fitted with an Autosteril unit (an automated device that can cycle 0.26% TAED perborate solution and sterile water for cleaning the water system between patients and overnight). Prior to testing the Autosteril and the 0.26% TAED perborate protocol on the Logos Jr Dental Unit (Castellini SpA, Italy), TAED perborate was used on a dental unit water system simulation device. METHODS: A dental unit water system simulation device equipped with four dental unit water systems and with naturally grown and mature biofilm contamination was used in this study (three treatment units and one control). One treatment group used a simulated 5 minutes contact with TAED perborate and sterile water for irrigation; the second used a simulated 5 minutes contact with TAED perborate and 2 ppm ClO2 for irrigation; the third used a simulated 5 minutes contact with TAED perborate and municipal water for irrigation. The control group used municipal water for irrigation with no cleaning/disinfection protocols. This protocol was repeated for 30 cycles. Laser scanning confocal microscopy (LSCM) was used to study the effects on natural and mature biofilms, and R2A agar used to quantify heterotrophic plate counts in the effluent irrigant. Antimicrobial efficacy was evaluated by challenging TAED perborate with microbes and spores (M. smegmatis and B. subtilis). Deleterious effects of the germicide were evaluated on metal and nonmetal parts of dental unit water systems. Heterotrophic plate counts using R2A agar and LSCM of the lines were conducted to assess biofilm and microbial control. RESULTS: Baseline water samples showed mean contamination >5.6 log10 cfu/ml. After initial cleaning, all three groups maintained mean contamination levels of less than 1.1 (SD <0.3) log10 cfu/ml. LSCM of baseline samples was positive for live biofilm in all groups. At the end of the study, viable biofilm was only present in the control. In the microbial challenge test, all vegetative organisms were killed within 30 seconds of contact, while spores were killed within 5 minutes. Corrosion was seen in metals used in US-manufactured dental unit materials, while not observed in those used in the Castellini Logos Jr dental unit. CONCLUSION: In this study, the TAED perborate protocol was effective in biofilm control and control of dental treatment water contamination. Use of sterile water or 2 ppm ClO2 along with TAED treatment also controlled planktonic contamination effectively. CLINICAL SIGNIFICANCE: Environmental biofilms contaminate dental unit water systems over time and affect the quality of dental treatment water. Contaminants include environmental biofilms, microbes, including gram-negative rods and endotoxins in high doses that are not of acceptable quality for treating patients. There are many germicidal protocols for treating this contamination and one such is the prescribed use of TAED perborate used in conjunction with sterile water for irrigation in the autosteril device, an integral component of the Castellini dental units for between patient decontamination of dental unit water systems. This study was conducted on an automated simulation dental unit water system to test the TAED perborate protocol's efficacy on naturally grown, mature environmental biofilms, it's efficacy on microbes and spores and it's effects on materials used in dental unit water systems. This translational research addresses both microbial control and material effects of TAED perborate in studying efficacy and possible deleterious effects and simulated use in dentistry. Currently, this antimicrobial use protocol is followed worldwide in the Castellini dental units that are used in day-to-day dental patient care.