Treatment of infection and inflammation associated with COVID-19, multi-drug resistant pneumonia and fungal sinusitis by nebulizing a nanosilver solution.

Solutions containing Ag0 nanoclusters, Ag+1, and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection. Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution. Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission. Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes.

Accrual and retention of diverse patients in psychosocial cancer clinical trials.

Background: Minority and older adult patients remain underrepresented in cancer clinical trials (CCTs). The current study sought to examine sociodemographic inequities in CCT interest, eligibility, enrollment, decline motivation, and attrition across two psychosocial CCTs for gynecologic, gastrointestinal, and thoracic cancers. Methods: Patients were approached for recruitment to one of two interventions: (1) a randomized control trial (RCT) examining effects of a cognitive-behavioral intervention targeting sleep, pain, mood, cytokines, and cortisol following surgery, or (2) a yoga intervention to determine its feasibility, acceptability, and effects on mitigating distress. Prospective RCT participants were queried about interest and screened for eligibility. All eligible patients across trials were offered enrollment. Patients who declined yoga intervention enrollment provided reasons for decline. Sociodemographic predictors of enrollment decisions and attrition were explored. Results: No sociodemographic differences in RCT interest were observed, and older patients were more likely to be ineligible. Eligible Hispanic patients across trials were significantly more likely to enroll than non-Hispanic patients. Sociodemographic factors predicted differences in decline motivation. In one trial, individuals originating from more urban areas were more likely to prematurely discontinue participation. Discussion: These results corroborate evidence of no significant differences in CCT interest across minority groups, with older adults less likely to fulfill eligibility criteria. While absolute Hispanic enrollment was modest, Hispanic patients were more likely to enroll relative to non-Hispanic patients. Additional sociodemographic trends were noted in decline motivation and geographical prediction of attrition. Further investigation is necessary to better understand inequities, barriers, and best recruitment practices for representative CCTs.

Chronic wounds: Treatment consensus.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs. Eighty percent or better concurrence among the panellists was considered a consensus. A large number of critical questions were discussed and agreed upon. Important takeaways included that wound care needs to be simplified to a point that it can be delivered by the patient or the patient's family. Another one was that telemonitoring, which has proved very useful during the COVID-19 pandemic, can help reduce the frequency of interventions by a visiting nurse or a wound care center. Defining patient expectations is critical to designing a successful treatment. Patient outcomes might include wound specific outcomes such as time to heal, wound size reduction, as well as improvement in quality of life. For those patients with expectations of healing, an aggressive approach to achieve that goal is recommended. When healing is not an expectation, such as in patients receiving palliative wound care, outcomes might include pain reduction, exudate management, odour management and/or other quality of life benefits to wound care.

Are Semi-Quantitative Clinical Cultures Inadequate? Comparison to Quantitative Analysis of 1053 Bacterial Isolates from 350 Wounds.

Early awareness and management of bacterial burden and biofilm is essential to wound healing. Semi-quantitative analysis of swab or biopsy samples is a relatively simple method for measuring wound microbial load. The accuracy of semi-quantitative culture analysis was compared to 'gold standard' quantitative culture analysis using 428 tissue biopsies from 350 chronic wounds. Semi-quantitative results, obtained by serial dilution of biopsy homogenates streaked onto culture plates divided into 4 quadrants representing occasional, light, moderate, and heavy growth, were compared to total bacterial load quantified as colony-forming units per gram (CFU/g). Light growth, typically considered an insignificant finding, averaged a clinically significant 2.5 × 105 CFU/g (SE = 6.3 × 104 CFU/g). Occasional growth (range: 102-106 CFU/g) and light growth (103-107 CFU/g) corresponded to quantitative values that spanned a 5-log range; moderate and heavy growth corresponded to a range of 4-log and 6-log, respectively, with a high degree of overlap in range of CFU/g per category. Since tissue biopsy and quantitative culture cannot be widely practiced and semi-quantitative analysis is unreliable, other clinically relevant approaches are required to determine wound bioburden and guide best management practices. Fluorescence imaging is a point-of-care technology that offers great potential in this field.

Development and assessment of a novel ex vivo corneal culture technique involving an agarose-based dome scaffold for use as a model of in vivo corneal wound healing in dogs and rabbits.

OBJECTIVE: To develop and assess a novel ex vivo corneal culture technique involving an agarose-based dome scaffold (ABDS) for use as a model of in vivo corneal wound healing in dogs and rabbits. SAMPLE: Corneas from clinically normal dogs (paired corneas from 8 dogs and 8 single corneas) and rabbits (21 single corneas). PROCEDURES: 8 single dog corneas (DCs), 1 DC from each pair, and 10 rabbit corneas (RCs) were wounded with an excimer laser; 1 DC from each pair and 11 RCs remained unwounded. Corneas were cultured for 21 days on ABDSs (8 pairs of DCs and all RCs) or on flat-topped scaffolds (8 single DCs). The surface area of corneal fluorescein retention was measured every 6 (DCs) or 12 (RCs) hours until full corneal epithelialization was detected. Changes in corneal clarity were evaluated at 0, 7, 14, and 21 days. RESULTS: Median time to full epithelialization for wounded dog and rabbit corneas was 48 and 60 hours, respectively; among wounded DCs, time to full epithelization did not differ by scaffold type. After 21 days of culture on ABDSs, all DCs and RCs that epithelialized developed a circular, diffuse, cloud-like pattern of optical haze, whereas DCs cultured on flat-topped scaffolds developed a focal, crater-like region of optical haze. All corneas on the ABDSs maintained convex curvature throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE: Wounded ex vivo DCs and RCs cultured on ABDSs reliably epithelialized, formed optical haze (consistent with in vivo wound healing), and maintained convex curvature. This culture technique may be adaptable to other species.

Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid.

AIM: The aim of this study is to assess the effectiveness of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDI) with a broad spectrum epigenetic activity, in improving filtration bleb survival as an adjunct therapy to glaucoma filtration surgery (GFS) in the rabbit model. MATERIALS AND METHODS: Eighteen New Zealand White rabbits underwent GFS in the left eye and were randomized to receive either a subconjunctival (SC) injection of 0.1 mL SAHA (9.25 µg/mL) or balanced saline solution (BSS) at the end of surgery, or a 3-minute intraoperative topical application of 0.4 mg/mL mitomycin-C (MMC). Bleb survival and histology were compared. RESULTS: Blebs of rabbits receiving injections of SAHA survived an average (mean ± SD) of 23.2 ± 2.7 days. SAHA rabbits showed a nonsignificant improvement over rabbits that received an injection of BSS, which had a mean survival time of 19.7 ± 2.7 days (p = 0.38) according to a one-way analysis of variance (ANOVA). Eyes receiving intraoperative topical MMC survived an average of 32.5 ± 3.3 days, which is significantly longer than both the control group treated with BSS (p = 0.01) and the experimental group treated with the SAHA (p = 0.0495). SAHA was well tolerated and showed no significant avascularity, necrosis, or conjunctival thinning. CONCLUSION: Although it was well tolerated, a single intraoperative injection of SAHA did not significantly prolong bleb survival in the rabbit model. CLINICAL SIGNIFICANCE: Epigenetic adjuncts hold promise for improving GFS outcome; however, future studies must continue to examine different administration protocols and dosages to substantiate their efficacy. HOW TO CITE THIS ARTICLE: Rodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37-41.

Interleukin-6 and body mass index, tobacco use, and sleep in gynecologic cancers.

OBJECTIVE: Elevated body mass index (BMI), tobacco use, and sleep disturbance are common health concerns among women with gynecologic cancers. The extent to which these factors are associated with systemic inflammation in gynecologic cancers is unknown. This is a significant literature gap given that (a) chronic, systemic inflammation may mediate relationships between behavioral health factors and cancer outcomes; and (b) elevated BMI, tobacco use, and sleep disturbances can be modified via behavioral interventions. This study examined Interleukin-6 (IL-6) relations with BMI, tobacco use history, and sleep disturbances in patients undergoing surgery for suspected gynecologic cancer. METHOD: Participants were 100 women (M age = 58.42 years, SD = 10.62 years) undergoing surgery for suspected gynecologic cancer. Smoking history was determined by participant self-report. Sleep quality/disturbance was assessed via the Pittsburgh Sleep Quality Index. BMI was abstracted from electronic health records. Presurgical serum IL-6 concentrations were determined using Enzyme-Linked Immunosorbent Assay. RESULTS: Controlling for the cancer type and stage, regression analyses revealed higher BMI, ß = 0.258, p = .007, and former/current smoking status, ß = 0.181, p = .046, were associated with higher IL-6. IL-6 did not differ between former and current smokers, ß = 0.008, p = .927. Global sleep quality, sleep latency, and sleep efficiency were not associated with IL-6. CONCLUSIONS: Higher BMI and any history of tobacco use predicted higher IL-6 among women undergoing surgery for suspected gynecologic cancers. Cognitive-behavioral interventions targeting primary and secondary obesity and tobacco use prevention may reduce systemic inflammation and optimize cancer outcomes in this population. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo.

Biofilms are prevalent in non-healing chronic wounds and implicated in delayed healing. Tolerance to antimicrobial treatments and the host's immune system leave clinicians with limited interventions against biofilm populations. It is therefore essential that effective treatments be rigorously tested and demonstrate an impact on biofilm across multiple experimental models to guide clinical investigations and protocols. Cadexomer iodine has previously been shown to be effective against biofilm in various in vitro models, against methicillin-resistant Staphylococcus aureus biofilm in mouse wounds, and clinically in diabetic foot ulcers complicated by biofilm. Similarities between porcine and human skin make the pig a favoured model for cutaneous wound studies. Two antiseptic dressings and a gauze control were assessed against mature biofilm grown on ex vivo pig skin and in a pig wound model. Significant reductions in biofilm were observed following treatment with cadexomer iodine across both biofilm models. In contrast, silver carboxymethylcellulose dressings had minimal impact on biofilm in the models, with similar results to the control in the ex vivo model. Microscopy and histopathology indicate that the depth of organisms in wound tissue may impact treatment effectiveness. Further work on the promising biofilm efficacy of cadexomer iodine is needed to determine optimal treatment durations against biofilm.

TIME CDST: an updated tool to address the current challenges in wound care.

Despite the understanding that wounds are a common problem affecting the individual, the health service and society as a whole, there continues to be a lack of a systematic, structured, evidence-based approach to wound management. The TIME principle was first published in 2003, 1 and has since been integrated by many into clinical practice and research. However, this tool has been criticised for its tendency to focus mainly on the wound rather than on the wider issues that the patient is presenting with. At an expert meeting held in London in 2018, this conundrum was addressed and the TIME clinical decision support tool (CDST) was elaborated upon. This article introduces the TIME CDST, explains why it is required and describes how its use is likely to benefit patients, clinicians and health-service organisations. It also explores the framework in detail, and shows why this simple and accessible framework is robust enough to facilitate consistency in the delivery of wound care and better patient outcomes. Finally, it outlines the next steps for the rollout, use and evaluation of the impact of the TIME CDST.

In Vivo Knockdown of the Herpes Simplex Virus 1 Latency-Associated Transcript Reduces Reactivation from Latency.

During herpes simplex virus (HSV) latency, most viral genes are silenced, with the exception of one region of the genome encoding the latency-associated transcript (LAT). This long noncoding RNA was originally described as having a role in enhancing HSV-1 reactivation. However, subsequent evidence showing that the LAT blocked apoptosis and promoted efficient establishment of latency suggested that its effects on reactivation were secondary to establishment. Here, we utilized an adeno-associated virus (AAV) vector to deliver a LAT-targeting hammerhead ribozyme to HSV-1-infected neurons of rabbits after the establishment of HSV-1 latency. The rabbits were then induced to reactivate latent HSV-1. Using this model, we show that decreasing LAT levels in neurons following the establishment of latency reduced the ability of the virus to reactivate. This demonstrates that the HSV-1 LAT RNA has a role in reactivation that is independent of its function in establishment of latency. In addition, these results suggest the potential of AAV vectors expressing LAT-targeting ribozymes as a potential therapy for recurrent HSV disease such as herpes stromal keratitis, a leading cause of infectious blindness.IMPORTANCE Herpes simplex virus (HSV) establishes a lifelong infection and remains dormant (latent) in our nerve cells. Occasionally HSV reactivates to cause disease, with HSV-1 typically causing cold sores whereas HSV-2 is the most common cause of genital herpes. The details of how HSV reactivates are largely unknown. Most of HSV's genes are silent during latency, with the exception of RNAs made from the latency-associated transcript (LAT) region. While viruses that make less LAT do not reactivate efficiently, these viruses also do not establish latency as efficiently. Here we deliver a ribozyme that can degrade the LAT to the nerve cells of latently infected rabbits using a gene therapy vector. We show that this treatment blocks reactivation in the majority of the rabbits. This work shows that the LAT RNA is important for reactivation and suggests the potential of this treatment as a therapy for treating HSV infections.

A Surfactant-Based Dressing to Treat and Prevent Acinetobacter baumannii Biofilms.

Previous work has demonstrated that a surfactant-based dressing was capable of eliminating any evidence of pre-existing biofilms from an ex vivo porcine skin wound model. Herein, the authors test both the surfactant's ability to prevent biofilm formation and its ability to eliminate Acinetobacter baumannii biofilms. To test biofilm formation inhibition, porcine skin explants were inoculated and incubated for 4 hours before treatment. The explants were then dressed with test or control materials. To test biofilm elimination, mature 3-day biofilms were established and then treated and wiped daily. Explants from each group were harvested daily, and total and biofilm-associated bacterial counts were generated up through day 3 posttreatment. The control explants developed a biofilm with ~106 CFU over the course of 3 days for each of the bacteria tested. The surfactant-treated samples had viable bacteria, but with the exception of a single time point for Staphylococcus aureus without silver sulfadiazine, there was no biofilm formation. Unlike previous results, the surfactants could not eliminate the A. baumannii biofilm, unless it was formulated with relevant antibiotics. The surfactant was effective in preventing the formation of biofilms over a 3-day period. Unlike the authors' previous results, the daily surfactant-based approach alone did not eliminate the A. baumannii biofilms unless relevant antibiotics were included. The data suggest that the surfactants can prevent biofilm formation, but that in the case of a confirmed A. baumannii biofilm, the surfactant must include antibiotics.

Effectiveness of a monofilament wound debridement pad at removing biofilm and slough: ex vivo and clinical performance.

OBJECTIVE: Removal of slough and other devitalised tissue is an important step in biofilm-based wound care (BBWC) and wound bed preparation. Debridement is key to management of both slough and biofilm, and a number of methods are available to achieve this, including surgical/sharp and mechanical debridement. Developments have led to products indicated for debridement of wounds, including a sterile pad consisting of monofilament fibres. Our aim is to examine the effectiveness of a monofilament wound debridement pad (WDP), Debrisoft. METHOD: We assessed the WDP, in laboratory tests, for the removal of mature biofilm from porcine dermal tissue in an ex vivo model, and the clinical management of sloughy wounds that would benefit from debridement. We used the UPPER score to determine the superficial infection status. RESULTS: The WDP was effective in removing biofilm from porcine dermal tissue. A case series of 10 patients with chronic wounds suggested that the WDP was beneficial in the removal of slough. All chronic wounds had slough and were cleaned weekly, for four weeks, using the MDP to achieve improved healing and a clean wound bed. The average wound size decreased from 8.09cm2 at baseline to 2.3cm2 at week four, with three wounds healed completely. Exudate was reduced, and the UPPER score improved in every patient. CONCLUSION: These results indicate that the WDP effectively debrides biofilm and slough, and contributes to care that follows the principles of wound bed preparation and BBWC.

Assessment of Topical Therapies for Improving the Optical Clarity Following Stromal Wounding in a Novel Ex Vivo Canine Cornea Model.

Purpose: To evaluate the effect of topical suberanilohydroxamic acid (SAHA) and 5-methyl-1-phenyl-2[1H]-pyridone (pirfenidone) on the degree of corneal haze in the stromal wounded ex vivo canine cornea. Methods: Twenty-four corneoscleral rims from normal dogs were uniformly wounded with an excimer laser and placed into culture medium with an air-liquid interface. The control group (n = 8) contained placebo-treated corneas. Treatment group 1 (n = 8) received SAHA topically every 6 hours. Treatment group 2 (n = 8) received pirfenidone topically every 6 hours. Each cornea was fluorescein stained and macrophotographed every 6 hours to assess epithelialization rate. All corneas were also macrophotographed weekly to assess optical clarity (haze). Images were analyzed for differences in pixel intensity between wounded (haze) and unwounded (nonhaze) regions, and haze surface area for each cornea was calculated. Results: The mean epithelialization time was 47.25 hours in the control group, 45.00 hours in the SAHA group, and 43.50 hours in the pirfenidone group, revealing no significant difference (P = 0.368). The median difference in pixel intensity between haze and nonhaze areas was 21.5 in the control group, 8.0 in the SAHA group, and 8.0 in the pirfenidone group, which is significant (P < 0.01). The median haze surface area was 12.96 mm2 in the control group, 5.70 mm2 in the SAHA group, and 5.92 mm2 in the pirfenidone group, which is significant (P < 0.01). Conclusions: Stromal-wounded ex vivo canine corneas exhibited greater optical clarity when treated with SAHA and pirfenidone than when placebo treated at 21 days. There was no significant difference in epithelialization rate between groups. Corneal contour was correlated with geographic haze distribution.

Proactive and Early Aggressive Wound Management: A Shift in Strategy Developed by a Consensus Panel Examining the Current Science, Prevention, and Management of Acute and Chronic Wounds.

Normal wound healing is accomplished through a series of well-coordinated, progressive events with overlapping phases. Chronic wounds are described as not progressing to healing or not being responsive to management in a timely manner. A consensus panel of multidisciplinary wound care professionals was assembled to (1) educate wound care practitioners by identifying key principles of the basic science of chronic wound pathophysiology, highlighting the impact of metalloproteinases and biofilms, as well as the role of the extracellular matrix; and (2) equip practitioners with a systematic strategy for the prevention and healing of acute injuries and chronic wounds based upon scientific evidence and the panel members' expertise. An algorithm is presented that represents a shift in strategy to proactive and early aggressive wound management. With proactive management, adjunct therapies are applied preemptively to acute injuries to reduce wound duration and risk of chronicity. For existing chronic wounds, early aggressive wound management is employed to break the pathophysiology cycle and drive wounds toward healing. Reducing bioburden through debridement and bioburden management and using collagen dressings to balance protease activity prior to the use of advanced modalities may enhance their effectiveness. This early aggressive wound management strategy is recommended for patients at high risk for chronic wound development at a minimum. In their own practices, the panel members apply this systematic strategy for all patients presenting with acute injuries or chronic wounds.

Dual-Phase Iontophoresis for the Delivery of Antisense Oligonucleotides.

In support of ongoing research in the study of corneal and skin wound healing, we sought to improve on previously published results by using iontophoresis to deliver RNA interference-based oligonucleotides. By using a electromechanics-based approach, we were able to devise a two-phase solution that separated the buffering solution from the antisense oligonucleotide (ASO) solution. The separation was obtained by making the drug solution a higher density than the buffer, leading it to sink directly onto the tissue surface. This change immediately decreased the distance that the ASO would have to travel before delivery. The changes enabled delivery into ex vivo skin and corneas in 10 or fewer minutes and into in vivo corneas in 5 min. In vivo studies demonstrated short-term bioavailability of at least 24 h, a lack of chemical or thermal injury, a lack of interference in the healing of a corneal injury, and an antisense effect till at least day 7, but not day 14. The only side-effect observed was postdelivery edema that was not present when the vehicle alone was iontophoresed. This suggests that electro-osmotic flow from the delivery chamber was not the mechanism, but that the delivered solute likely increased the tissue's osmolarity. These results support the continued development and utilization of this ASO delivery approach in research-grade oligonucleotides to probe molecular biological pathways and in support of testing therapeutic ASOs in the skin and cornea.

Connective tissue growth factor is not necessary for haze formation in excimer laser wounded mouse corneas.

We sought to determine if connective tissue growth factor (CTGF) is necessary for the formation of corneal haze after corneal injury. Mice with post-natal, tamoxifen-induced, knockout of CTGF were subjected to excimer laser phototherapeutic keratectomy (PTK) and the corneas were allowed to heal. The extent of scaring was observed in non-induced mice, heterozygotes, and full homozygous knockout mice and quantified by macrophotography. The eyes from these mice were collected after euthanization for re-genotyping to control for possible Cre-mosaicism. Primary corneal fibroblasts from CTGF knockout corneas were established in a gel plug assay. The plug was removed, simulating an injury, and the rate of hole closure and the capacity for these cells to form light reflecting cells in response to CTGF and platelet-derived growth factor B (PDGF-B) were tested and compared to wild-type cells. We found that independent of genotype, each group of mice was still capable of forming light reflecting haze in the cornea after laser ablation (p = 0.40). Results from the gel plug closure rate in primary cell cultures of knockout cells were not statistically different from serum starved wild-type cells, independent of treatment. Compared to the serum starved wild-type cells, stimulation with PDGF-BB significantly increased the KO cell culture's light reflection (p = 0.03). Most interestingly, both reflective cultures were positive for α-SMA, but the cellular morphology and levels of α-SMA were distinct and not in proportion to the light reflection seen. This new work demonstrates that corneas without CTGF can still form sub-epithelial haze, and that the light reflecting phenotype can be reproduced in culture. These data support the possibilities of growth factor redundancy and that multiple pro-haze pathways exist.

Nitroxoline: a broad-spectrum biofilm-eradicating agent against pathogenic bacteria.

Bacterial biofilms are surface-attached communities of slow-growing or non-replicating bacteria tolerant to conventional antibiotic therapies. Although biofilms are known to occur in ca. 80% of all bacterial infections, no therapeutic agent has been developed to eradicate bacteria housed within biofilms. We have discovered that nitroxoline, an antibacterial agent used to treat urinary tract infections, displays broad-spectrum biofilm-eradicating activities against major human pathogens, including drug-resistant Staphylococcus aureus and Acinetobacter baumannii strains. In this study, the effectiveness of nitroxoline to eradicate biofilms was determined using an in vitro [minimum biofilm eradication concentration (MBEC) = 46.9 µM against A. baumannii] and ex vivo porcine skin model (2-3 log reduction in viable biofilm cells). Nitroxoline was also found to eradicate methicillin-resistant S. aureus (MRSA) persister cells in non-biofilm (stationary) cultures, whereas vancomycin and daptomycin were found to be inactive. These findings could lead to effective, nitroxoline-based therapies for biofilm-associated infections.

Testing the influence of surfactant-based wound dressings on proteinase activity.

Proteinases are enzymes that can digest other proteins. In chronic wounds, a sub-class of these enzymes with the ability to degrade the extracellular matrix (matrix metalloproteinases, MMPs) have been found to both inhibit healing and to be able to aid in enzymatically debriding a wound. Enzymatic debridement using the enzymes present in a wound is generally called autolytic debridement. Clinicians seeking to employ autolytic debridement typically use occlusive materials such as medical honey, alginate dressings and other occlusive dressings. A relatively new class of gel dressings comprised of surfactants are now available for clinical use. A variety of surfactants are used in the study of MMP biochemistry. Surfactants can deactivate MMPs or can enhance their activity, depending on the surfactant. In order to begin to understand how the MMPs found in chronic wounds would respond to these new dressings, we tested a serial dilution series of two of the currently available surfactant-based dressings to determine their effects on four separate MMPs. The dose-response versus MMP activity of bacterial collagenase, host-derived MMP-8 and MMPs-2 and -9 was assessed using a simple mix-and-read fluorescent peptide activity assay. The enzyme's native activity in the absence of the gel was used to compare against the surfactant-treated samples. We found that the surfactant affected the proteinase activity differently for each enzyme. The activity of the bacterial collagenase was increased at low concentrations but slightly inhibited as the concentrations increased. The host MMP-8 collagenase responded similarly in that it was inhibited at higher concentrations. Interestingly, both MMP gelatinases presented with substantially increased activities, with MMP-2 increased to 200% of native activity, while MMP-9 presented with an increase of 300% activity over the same concentration range. MMPs appear to respond to a surfactant-based gel dressing differentially, with the MMP most commonly elevated in chronic wounds having the highest boost to activity. In wounds with elevated MMPs, our data suggest that the use of these surfactant-based dressings would be expected to enhance the activity of MMPs 2 and 9 gelatinases while simultaneously inhibiting MMP-8 collagenase. Hypothetically, this imbalanced effect would support a protection of the native dermal collagen and removal of denatured materials. However, the demonstration of these anticipated consequences is still being investigated.

A surfactant-based wound dressing can reduce bacterial biofilms in a porcine skin explant model.

Bacterial biofilms have been found in many, if not all, chronic wounds. Their excessive extracellular matrix secretion and the metabolic changes that they undergo render them highly tolerant of many antibiotic and antimicrobial treatments. Physical removal and/or disruption are a common approach to treating wounds suspected of having bacterial biofilms. While many of these techniques use mechanical energy as the primary means of removal, we have begun to investigate if surfactants could facilitate the removal of bacterial biofilms, or if they might sensitise the biofilms to antimicrobial interventions. We tested a new surfactant-based wound gel on an ex vivo porcine skin explant model infected with a functionally tolerant 3-day biofilm. The wounds were dressed with a surfactant-based gel directly on the wound or with moistened gauze. The wounds were then wiped daily with moistened gauze, and the gel or gauze was re-applied. Each day, an explant from each group was harvested and tested for total viable bacteria counts and viable biofilm-protected bacteria counts. The results show that daily wiping with moistened gauze led to an initial decrease of bacteria, but by day 3, the biofilm had been fully re-established to the same level prior to the beginning of treatment. For the surfactant-based treatment, there was no detectable functional biofilm after the first treatment. The gauze control, which was also subjected to daily wiping, still contained functional biofilms, indicating that this result was not due to wiping alone. The total bacteria in the surfactant-treated explants steadily decreased through day 3, when there were no detectable bacteria, while the wiping-only control bacteria counts remained steady. The use of a moist gauze to wipe the visually apparent slime off of a wound appears to be insufficient to reduce biofilm over a 3-day period. Daily application of the surfactant gel dressing and wiping reduced the biofilm to undetectable levels within 3 days in a skin explant model. A 3-day regimen of dressing the wound model with a surfactant gel followed by gentle removal of the gel by wiping with a moistened gauze appears to be a simple and adequate approach to removing a bacterial biofilm infection in an ex vivo model. Additional clinical evidence is needed to determine if this promising approach can perform the same in clinically infected chronic wounds.