Leila Cuttle

Collagen in the scarless fetal skin wound: Detection with Picrosirius-polarization

Our group has developed an ovine model of deep dermal, partial‐thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross‐linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a “response” to burn injury.

Vitronectin: Growth Factor Complexes Hold Potential as a Wound Therapy Approach

Topical administration of growth factors has displayed some potential in wound healing, but variable efficacy, high doses, and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple growth factors and extracellular matrix (ECM) proteins. We report herein that complexes comprising IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes in two- and three-dimensional in vitro cell models and are active, even in the presence of wound fluid. Moreover, these responses require activation of both the IGF receptor and the VN-binding alpha(v) integrins. Further, we assessed the complexes as a topical agent in the treatment of deep dermal partial thickness burns in a porcine model. This pilot study revealed that the complexes may hold promise as a wound healing therapy. Critically, the significant responses observed in vitro and the encouraging preliminary data in vivo were obtained with nanogram doses of growth factors. This suggests that coupling delivery of growth factors to ECM proteins such as VN may ultimately prove to be a more effective strategy for developing a wound healing therapy.

A review of first aid treatments for burn injuries

Throughout history there have been many different and sometimes bizarre treatments prescribed for burns. Unfortunately many of these treatments still persist today, although they often do not have sufficient evidence to support their use. This paper reviews common first aid and pre-hospital treatments for burns (water--cold or warm, ice, oils, powders and natural plant therapies), possible mechanisms whereby they might work and the literature which supports their use. From the published work to date, the current recommendations for the first aid treatment of burn injuries should be to use cold running tap water (between 2 and 15 degrees C) on the burn, not ice or alternative plant therapies.

The efficacy of an augmented virtual reality system to alleviate pain in children undergoing burns dressing changes : A randomised controlled trial

In children, the pain and anxiety associated with acute burn dressing changes can be severe, with drug treatment alone frequently proving to be inadequate. Virtual reality (VR) systems have been successfully trialled in limited numbers of adult and paediatric burn patients. Augmented reality (AR) differs from VR in that it overlays virtual images onto the physical world, instead of creating a complete virtual world. This prospective randomised controlled trial investigated the use of AR as an adjunct to analgesia and sedation in children with acute burns. Forty-two children (30 male and 12 female), with an age range of 3-14 years (median age 9 years) and a total burn surface area ranging from 1 to 16% were randomised into a treatment (AR) arm and a control (basic cognitive therapy) arm after administration of analgesia and/or sedation. Pain scores, pulse rates (PR), respiratory rates (RR) and oxygen saturations (SaO2) were recorded pre-procedurally, at 10 min intervals and post-procedurally. Parents were also asked to grade their childs overall pain score for the dressing change. Mean pain scores were significantly lower (p=0.0060) in the AR group compared to the control group, as were parental pain assessment scores (p=0.015). Respiratory and pulse rates showed significant changes over time within groups, however, these were not significantly different between the two study groups. Oxygen saturation did not differ significantly over time or between the two study groups. This trial shows that augmented reality is a useful adjunct to pharmacological analgesia.

Antimicrobial efficacy of a novel silver hydrogel dressing compared to two common silver burn wound dressings: Acticoat™ and PolyMem Silver ®

A novel burn wound hydrogel dressing has been previously developed which is composed of 2-acrylamido-2-methylpropane sulfonic acid sodium salt with silver nanoparticles. This study compared the antimicrobial efficacy of this novel dressing to two commercially available silver dressings; Acticoat™ and PolyMem Silver(®). Three different antimicrobial tests were used: disc diffusion, broth culture, and the Live/Dead(®) Baclight™ bacterial viability assay. Burn wound pathogens (P. aeruginosa, MSSA, A. baumannii and C. albicans) and antibiotic resistant strains (MRSA and VRE) were tested. All three antimicrobial tests indicated that Acticoat™ was the most effective antimicrobial agent, with inhibition zone lengths of 13.9-18.4mm. It reduced the microbial inocula below the limit of detection (10(2)CFU/ml) and reduced viability by 99% within 4h. PolyMem Silver(®) had no zone of inhibition for most tested micro-organisms, and it also showed poor antimicrobial activity in the broth culture and Live/Dead(®) Baclight™ assays. Alarmingly, it appeared to promote the growth of VRE. The silver hydrogel reduced most of the tested microbial inocula below the detection limit and decreased bacterial viability by 94-99% after 24h exposure. These results support the possibility of using this novel silver hydrogel as a burn wound dressing in the future.

An Audit of First-Aid Treatment of Pediatric Burns Patients and Their Clinical Outcome

This study describes the first aid used and clinical outcomes of all patients who presented to the Royal Children’s Hospital, Brisbane, Australia in 2005 with an acute burn injury. A retrospective audit was performed with the charts of 459 patients and information concerning burn injury, first-aid treatment, and clinical outcomes was collected. First aid was used on 86.1% of patients, with 8.7% receiving no first aid and unknown treatment in 5.2% of cases. A majority of patients had cold water as first aid (80.2%), however, only 12.1% applied the cold water for the recommended 20 minutes or longer. Recommended first aid (cold water for ≥20 minutes) was associated with significantly reduced reepithelialization time for children with contact injuries (P = .011). Superficial depth burns were significantly more likely to be associated with the use of recommended first aid (P = .03). Suboptimal treatment was more common for children younger than 3.5 years (P < .001) and for children with friction burns. This report is one of the few publications to relate first-aid treatment to clinical outcomes. Some positive clinical outcomes were associated with recommended first-aid use; however, wound outcomes were more strongly associated with burn depth and mechanism of injury. There is also a need for more public awareness of recommended first-aid treatment.

The optimal duration and delay of first aid treatment for deep partial thickness burn injuries.

Using our porcine model of deep dermal partial thickness burn injury, various durations (10min, 20min, 30min or 1h) and delays (immediate, 10min, 1h, 3h) of 15 degrees C running water first aid were applied to burns and compared to untreated controls. The subdermal temperatures were monitored during the treatment and wounds observed weekly for 6 weeks, for re-epithelialisation, wound surface area and cosmetic appearance. At 6 weeks after the burn, tissue biopsies were taken of the scar for histological analysis. Results showed that immediate application of cold running water for 20min duration is associated with an improvement in re-epithelialisation over the first 2 weeks post-burn and decreased scar tissue at 6 weeks. First aid application of cold water for as little as 10min duration or up to 1h delay still provides benefit.

Silver deposits in cutaneous burn scar tissue is a common phenomenon following application of a silver dressing

Background:  Silver dressings have been widely and successfully used to prevent cutaneous wounds, including burns, chronic ulcers, dermatitis and other cutaneous conditions, from infection. However, in a few cases, skin discolouration or argyria‐like appearances have been reported. This study investigated the level of silver in scar tissue post‐burn injury following application of Acticoat™, a silver dressing.

Silver absorption on burns after the application of Acticoat: data from pediatric patients and a porcine burn model.

Silver dressings have been widely used to successfully prevent burn wound infection and sepsis. However, a few case studies have reported the functional abnormality and failure of vital organs, possibly caused by silver deposits. The aim of this study was to investigate the serum silver level in the pediatric burn population and also in several internal organs in a porcine burn model after the application of Acticoat™. A total of 125 blood samples were collected from 46 pediatric burn patients. Thirty-six patients with a mean of 13.4% TBSA burns had a mean peak serum silver level of 114 &mgr;g/L, whereas 10 patients with a mean of 1.85% TBSA burns had an undetectable level of silver (<5.4 &mgr;g/L). Overall, serum silver levels were closely related to burn sizes. However, the highest serum silver was 735 &mgr;g/L in a 15-month-old toddler with 10% TBSA burns and the second highest was 367 &mgr;g/L in a 3-year old with 28% TBSA burns. In a porcine model with 2% TBSA burns, the mean peak silver level was 38 &mgr;g/L at 2 to 3 weeks after application of Acticoat™ and was then significantly reduced to an almost undetectable level at 6 weeks. Of a total of four pigs, silver was detected in all four livers (1.413 &mgr;g/g) and all four hearts (0.342 &mgr;g/g), three of four kidneys (1.113 &mgr;g/g), and two of four brains (0.402 &mgr;g/g). This result demonstrated that although variable, the level of serum silver was positively associated with the size of burns, and significant amounts of silver were deposited in internal organs in pigs with only 2% TBSA burns, after application of Acticoat™.

Cytotoxicity testing of burn wound dressings, ointments and creams: A method using polycarbonate cell culture inserts on a cell culture system

UNLABELLED We have developed a method to test the cytotoxicity of wound dressings, ointments, creams and gels used in our Burn Centre, by placing them on a permeable Nunc™ Polycarbonate cell culture insert, incubated with a monolayer of cells (HaCaTs and primary human keratinocytes). METHODS We performed two different methods to determine the relative toxicity to cells. (1) Photo visualisation: The dressings or compounds were positioned on the inserts membrane which was placed onto the monolayer tissue culture plate. After 24 h the surviving adherent cells were stained with Toluidine Blue and photos of the plates were taken. The acellular area of non-adherent dead cells which had been washed off with buffer was measured as a percentage of the total area of the plate. (2) Cell count of surviving cells: After 24 h incubation with the test material, the remaining cells were detached with trypsin, spun down and counted in a Haemocytometer with Trypan Blue, which differentiates between live and dead cells. RESULTS Seventeen products were tested. The least cytotoxic products were Melolite™, White soft Paraffin™ and Chlorsig1% Ointment. Some cytotoxicity was shown with Jelonet™, Mepitel(®), PolyMem(®), DuoDerm(®) and Xeroform™. The most cytotoxic products included those which contained silver or Chlorhexidine and Paraffin Cream™ a moisturizer which contains the preservative Chlorocresol. CONCLUSION This in vitro cell culture insert method allows testing of agents without direct cell contact. It is easy and quick to perform, and should help the clinician to determine the relative cytotoxicity of various dressings and the optimal dressing for each individual wound.