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. METHODS A porcine deep dermal partial thickness burn model was used. Burn wounds were treated with this silver dressing until completion of re-epithelialization, and silver levels were measured in a total of 160 scars and normal tissues. RESULTS The mean level of silver in scar tissue covered with silver dressings was 136 microg/g, while the silver level in normal skin was less than 0.747 microg/g. A number of wounds had a slate-grey appearance, and dissection of the scars revealed brown-black pigment mostly in the middle and deep dermis within the scar. The level of silver and the severity of the slate-grey discolouration were correlated with the length of time of the silver dressing application. CONCLUSIONS These results show that silver deposition in cutaneous scar tissue is a common phenomenon, and higher levels of silver deposits and severe skin discolouration are correlated with an increase in the duration of this silver dressing application.

Fetuin-A : a major fetal serum protein that promotes "wound closure" and scarless healing [Letter to the Editor]

Burn-wound healing is a dynamic, interactive process involving a number of cellular and molecular events and is characterized by inflammation, granulation tissue formation, re-epithelialization, and tissue remodeling (Greenhalgh, 2002; Linares, 2002). Unlike incisional-wound healing, it also requires extensive re-epithelialization due to a predominant horizontal loss of tissue and often heals with abnormal scarring when burns involve deep dermis. The early mammalian fetus has the remarkable ability to regenerate normal epidermis and dermis and to heal dermal incisional wounds with no signs of scarring. Extensive research has indicated that scarless healing appears to be intrinsic to fetal skin (McCallion and Ferguson, 1996; Ferguson and O’Kane, 2004). Previously, we reported a fetal burn model, in which 80-day-old ovine fetuses (gestation¼ 145–153 days) healed deep dermal partial thickness burns without scars, whereas postnatal lambs healed equal depth burns with significant scarring (Cuttle et al., 2005; Fraser et al., 2005). This burn model provided early evidence that fetal skin has the capacity to repair and restore dermal horizontal loss, not just vertical injuries.

Conservative surgical debridement as a burn treatment : supporting evidence from a porcine burn model

In thermal deep-dermal burns, surgical debridement is normally used in conjunction with skin grafting or skin substitutes and debridement alone as a burn treatment is not usually practiced. The current study addresses whether or not debridement alone would enhance burn wound healing on small deep-dermal-partial thickness burns. This was a prospective and blinded experimental trial using a porcine deep-dermal-partial thickness burn model. Four burns, approximately 50 cm(2) in size, were created on each of eight pigs. Two burns from each pig were immediately surgically debrided and the other two were not debrided as the internal control. Hydrate gel together with paraffin gauze were used to cover the burns for four pigs and silver dressings for the other four. Clinical assessment of wound healing was conducted over a 6-week period. Skin samples were collected at the end of the experiment and histopathological evaluation was performed. The results show thinner scar formation and lower scar height in the debrided compared with nondebrided wounds in the hydrate gel/paraffin gauze groups. There were no statistically significant differences in wound healing assessment between the debrided and nondebrided wounds dressed with silver dressings. This study provides supporting evidence that immediate debridement with an appropriate dressing and without skin grafting may promote wound healing, suggesting its potential benefit for clinical patients.

Matrix metalloproteinases during wound healing - a double edged sword

The extracellular matrix (ECM) provides a framework for cells and gives skin its tensile strength and elasticity. Loss of its integrity necessitates the clearing of damaged components and the deposition of firstly a provisional matrix and later remodelling of the ECM to support a functionally intact tissue. Matrix metalloproteinases (MMPs) are an important family of enzymes that function in the breakdown of the ECM and modulate the function of many biologically active molecules housed in the ECM. Through their enzymatic actions MMPs play a role in fundamental processes such as immune cell infiltration and ECM remodelling during wound repair. Their tight control is necessary for timely wound healing and excessive MMP activity participates in the development and persistence of chronic wounds, while reduced activity contributes to fibrosis. A number of inhibitors have been designed to target this activity and improve wound healing with limited success. Novel strategies are currently being investigated to improve wound healing by targeting MMP modulating molecules.

Acticoat™ : A cost-effective and evidence-based dressing strategy [Letter to the Editor]

We thank Dr. Burd et al. for taking an interest in our paper [1]. The retrospective cohort study was performed and published for two reasons. Firstly, we wished to compare and contrast the use of Acticoat™ and Silvazine™, and secondly we wished to demonstrate how one's practice can be dramatically altered by a change in dressing used. We found that Acticoat™ was safe and easy to use, caused less trauma to patients, required less frequent dressing changes and enabled treatment to be conducted on an outpatient, rather than an inpatient basis. During the period of Acticoat™ treatment we also saw a dramatic reduction in grafting requirements and also in the need for long-term scar management. Burd et al. correctly state that silver-based dressings are now more widely available, however many burn centres in the world continue to use silver sulphadiazine with daily baths. We therefore feel that a comparison is very relevant and useful. Prospective, randomised clinical trials of a range of silver-based dressings would indeed be useful, and hopefully Dr. Burd and colleagues will take up their own suggestion and perform these studies...

Mathematical investigation of the interactions between the inflammatory response and mechanical aspects of dermal wound repair

Dermal wound repair involves complex interactions between cells, cytokines and mechanics to close injuries to the skin. In particular, we investigate the contribution of fibroblasts, myofibroblasts, TGFβ, collagen and local tissue mechanics to wound repair in the human dermis. We develop a morphoelastic model where a realistic representation of tissue mechanics is key, and a fibrocontractive model that involves a reasonable approximation to the true kinetics of the important bioactive species. We use each of these descriptions to elucidate the mechanisms that generate pathologies such as hypertrophic scars, contractures and keloids. We find that for hypertrophic scar and contracture development, factors regulating the myofibroblast phenotype are critical, with heightened myofibroblast activation, reduced myofibroblast apoptosis or prolonged inflammation all predicted as mediators for scar hypertrophy and contractures. Prevention of these pathologies is predicted when myofibroblast apoptosis is induced, myofibroblast activation is blocked or TGFβ is neutralised. To investigate keloid invasion, we develop a caricature representation of the fibrocontractive model and find that TGFβ spread is the driving factor behind keloid growth. Blocking activation of TGFβ is found to cause keloid regression. Thus, we recommend myofibroblasts and TGFβ as targets for clinicians when developing intervention strategies for prevention and cure of fibrotic scars.

Proteomics in chronic wound research : potentials in healing and health

Chronic wounds, such as venous and diabetic leg ulcers, represent a significant health and financial burden to individuals and healthcare systems. In worst case scenarios this condition may require the amputation of an affected limb, with significant impact on patient quality of life and health. Presently there are no clinical biochemical analyses used in the diagnosis and management of this condition; moreover few biochemical therapies are accessible to patients. This presents a significant challenge in the efficient and efficacious treatment of chronic wounds by medical practitioners. A number of protein-centric investigations have analysed the wound environment and implicated a suite of molecular species predicted to be involved in the initiation or perpetuation of the condition. However, comprehensive proteomic investigation is yet to be engaged in the analysis of chronic wounds for the identification of molecular diagnostic/prognostic markers of healing or therapeutic targets. This review examines clinical chronic wound research and recommends a path towards proteomic investigation for the discovery of medically significant targets. Additionally, the supplementary documents associated with this review provide the first comprehensive summary of protein-centric, small molecule and elemental analyses in clinical chronic wound research.

On the efficacy of key corporate governance recommendations in mid-tier companies : window-dressing or value-adding?

This paper examins the relationship between firm performance and key board and audit committee variables in a sample of mid-tier listed Australian firms. Unlike the UK where the corporate governance Code specifically outlines special arrangements for companies outside the FTSE 350 index, the ASX Corporate Governance recommendations make no special provisions for mid-tier companies. Consequently, mid-tier Australian companies may be expending scarce resources in conforming with recommendations that are not value-creating.

Novel solutions for a model of wound healing angiogenesis

We prove the existence of novel, shock-fronted travelling wave solutions to a model of wound healing angiogenesis studied in Pettet et al (2000 IMA J. Math. App. Med. 17 395–413) assuming two conjectures hold. In the previous work, the authors showed that for certain parameter values, a heteroclinic orbit in the phase plane representing a smooth travelling wave solution exists. However, upon varying one of the parameters, the heteroclinic orbit was destroyed, or rather cut-off, by a wall of singularities in the phase plane. As a result, they concluded that under this parameter regime no travelling wave solutions existed. Using techniques from geometric singular perturbation theory and canard theory, we show that a travelling wave solution actually still exists for this parameter regime. We construct a heteroclinic orbit passing through the wall of singularities via a folded saddle canard point onto a repelling slow manifold. The orbit leaves this manifold via the fast dynamics and lands on the attracting slow manifold, finally connecting to its end state. This new travelling wave is no longer smooth but exhibits a sharp front or shock. Finally, we identify regions in parameter space where we expect that similar solutions exist. Moreover, we discuss the possibility of more exotic solutions.

Improving wound management for residents in Residential Aged Care Facilities: National dissemination and implementation of the evidence based Champions for Skin Integrity Program

Overview The incidence of skin tears, pressure injuries and chronic wounds increases with age [1-4] and therefore is a serious issue for staff and residents in Residential Aged Care Facilities (RACFs). A pilot project funded in Round 2 of the Encouraging Best Practice in Residential Aged Care (EBPRAC) program by the then Australian Government Department of Health and Ageing found that a substantial proportion of residents in aged care facilities experienced pressure injuries, skin tears or chronic wounds. It also found the implementation of the evidence based Champions for Skin Integrity (CSI) model of wound care was successful in significantly decreasing the prevalence and severity of wounds in residents, improving staff skills and knowledge of evidence based wound management, increasing staff confidence with wound management, increasing implementation of evidence based wound management and prevention strategies, and increasing staff awareness of their roles in evidence based wound care at all levels [5]. Importantly, during the project, the project team developed a resource kit on evidence based wound management. Two critical recommendations resulting from the project were that: - The CSI model or a similar strategic approach should be implemented in RACFs to facilitate the uptake of evidence based wound management and prevention - The resource kit on evidence based wound management should be made available to all Residential Aged Care Facilities and interested parties A proposal to disseminate or rollout the CSI model of wound care to all RACFs across Australia was submitted to the department in 2012. The department approved funding from the Aged Care Services Improvement Healthy Ageing Grant (ACSIHAG) at the same time as the Round 3 of the Encouraging Better Practice in Aged Care (EBPAC) program. The dissemination involved two crucial elements: 1. The updating, refining and distribution of a Champions for Skin Integrity Resource Kit, more commonly known as a CSI Resource Kit and 2. The presentation of intensive one day Promoting Healthy Skin “Train the Trainer” workshops in all capital cities and major regional towns across Australia Due to demand, the department agreed to fund a second round of workshops focussing on regional centres and the completion date was extended to accommodate the workshops. Later, the department also decided to host a departmental website for a number of clinical domains, including wound management, so that staff from the residential aged care sector had easy access to a central repository of helpful clinical resource material that could be used for improving the health and wellbeing of their older adults, consumers and carers. CSI Resource Kit Upgrade and Distribution: At the start of the project, a full evidence review was carried out on the material produced during the EBPRAC-CSI Stage 1 project and the relevant evidence based changes were made to the documentation. At the same time participants in the EBPRAC-CSI Stage 1 project were interviewed for advice on how to improve the resource material. Following this the documentation, included in the kit, was sent to independent experts for peer review. When this process was finalised, a learning designer and QUT’s Visual Communications Services were engaged to completely refine and update the design of the resources, and combined resource kit with the goal of keeping the overall size of the kit suitable for bookshelf mounting and the cost at reasonable levels. Both goals were achieved in that the kit is about the same size as a 25 mm A4 binder and costs between $19.00 and $28.00 per kit depending on the size of the print run. The dissemination of the updated CSI resource kit was an outstanding success. Demand for the kits was so great that a second print run of 2,000 kits was arranged on top of the initial print run of 4,000 kits. All RACFs across Australia were issued with a kit, some 2,740 in total. Since the initial distribution another 1,100 requests for kits has been fulfilled as well as 1,619 kits being distributed to participants at the Promoting Healthy Skin workshops. As the project was winding up a final request email was sent to all workshop participants asking if they required additional kits or resources to distribute the remaining kits and resources. This has resulted in requests for 200 additional kits and resources. Feedback from the residential aged care sector and other clinical providers who have interest in wound care has been very positive regarding the utility of the kit, (see Appendix 4). Promoting Healthy Skin Workshops The workshops also exceeded the project team’s initial objective. Our goal of providing workshop training for staff from one in four facilities and 450 participants was exceeded, with overwhelming demand for workshop places resulting in the need to provide a second round of workshops across Australia. At the completion of the second round, 37 workshops had been given, with 1286 participants, representing 835 facilities. A number of strategies were used to promote the workshops ranging from invitations included in the kit, to postcard mail-outs, broadcast emailing to all facilities and aged care networks and to articles and paid advertising in aged care journals. The most effective method, by far, was directly phoning the facilities. This enabled the caller to contact the relevant staff member and enlist their support for the workshop. As this is a labour intensive exercise, it was only used where numbers needed bolstering, with one venue rising from 3 registrants before the calls to 53 registrants after. The workshops were aimed at staff who had the interest and the capability of implementing evidence-based wound management within their facility or organisation. This targeting was successful in that a large proportion (68%) of participants were Registered Nurses, Nurse Managers, Educators or Consultants. Twenty percent were Endorsed Enrolled Nurses with the remaining 12% being made up of Personal Care Workers or Allied Health Professionals. To facilitate long term sustainability, the workshop employed train-the-trainer strategies. Feedback from the EBPRAC-CSI Stage 1 interviews was used in the development of workshop content. In addition, feedback from the workshop conducted at the end of the EBPRAC-CSI Stage 1 project suggested that change management and leadership training should be included in the workshops. The program was trialled in the first workshop conducted in Brisbane and then rolled out across Australia. Participants were asked to complete pre and post workshop surveys at the beginning and end of the workshop to determine how knowledge and confidence improved over the day. Results from the pre and post surveys showed significant improvements in the level of confidence in attendees’ ability to implement evidence based wound management. The results also indicated a significant increase in the level of confidence in ability to implement change within their facility or organisation. This is an important indication that the inclusion of change management/leadership training with clinical instruction can increase staff capacity and confidence in translating evidence into practice. To encourage the transfer of the evidence based content of the workshop into practice, participants were asked to prepare an Action Plan to be followed by a simple one page progress report three months after the workshop. These reports ranged from simple (e.g. skin moisturising to prevent skin tears), to complex implementation plans for introducing the CSI model across the whole organisation. Outcomes described in the project reports included decreased prevalence of skin tears, pressure injuries and chronic wounds, along with increased staff and resident knowledge and resident comfort. As stated above, some organisations prepared large, complex plans to roll out the CSI model across their organisation. These plans included a review of the organisation’s wound care system, policies and procedures, the creation of new processes, the education of staff and clients, uploading education and resource material onto internal electronic platforms and setting up formal review and evaluation processes. The CSI Resources have been enthusiastically sought and incorporated into multiple health care settings, including aged care, acute care, Medicare Local intranets (e.g. Map of Medicine e-pathways), primary health care, community and home care organisations, education providers and New Zealand aged and community health providers. Recommendations: Recommendations for RACFs, aged care and health service providers and government  Skin integrity and the evidence-practice gap in this area should be recognised as a major health issue for health service providers for older adults, with wounds experienced by up to 50% of residents in aged care settings (Edwards et al. 2010). Implementation of evidence based wound care through the Champions for Skin Integrity model in this and the pilot project has demonstrated the prevalence of wounds, wound healing times and wound infections can be halved.  A national program and Centre for Evidence Based Wound Management should be established to: - expand the reach of the model to other aged care facilities and health service providers for older adults - sustain the uptake of models such as the Champions for Skin Integrity (CSI) model - ensure current resources, expertise and training are available for consumers and health care professionals to promote skin integrity for all older adults  Evidence based resources for the CSI program and similar projects should be reviewed and updated every 3 – 4 years as per NH&MRC recommendations  Leadership and change management training is fundamental to increasing staff capacity, at all levels, to promote within-organisation dissemination of skills and knowledge gained from projects providing evidence based training Recommendations for future national dissemination projects  A formal program of opportunities for small groups of like projects to share information and resources, coordinate activities and synergise education programs interactively would benefit future national dissemination projects - Future workshop programs could explore an incentive program to optimise attendance and reduce ‘no shows’ - Future projects should build in the capacity and funding for increased follow-up with workshop attendees, to explore the reasons behind those who are unable to translate workshop learnings into the workplace and identify factors to address these barriers.

Wound healing from the outback: novel wound healing therapeutics from native Australian plants

Introduction Chronic wounds are an area of major concern. The on-going and in-direct costs are substantial, reaching far beyond the costs of the hospitalization and associated care. As a result, pharmacological therapies have been developed to address treatment insufficiencies, however, the availability of drugs capable of promoting the wound repair process still remain limited. The wound healing properties of various herbal plants is well recognised amongst indigenous Australians. Hence, based on traditional accounts, we evaluated the wound healing potential of two Australian native plants. Methods Bioactive compounds were methanol extracted from dried plant leaves that were commercially sourced. Primary keratinocyte (Kc) and fibroblast (Fib) cells (denoted as Kc269, Kc274, Kc275, Kc276 and Fib274) obtained from surgical discarded tissue were cultured in 48-well plates and incubated (37⁰C, 5% CO2) overnight. The growth media was discarded and replaced with fresh growth media plus various concentrations (15.12 µg/mL, 31.25 µg/mL, 62.5 µg/mL, 125 µg/mL, 250 µg/mL and 500 µg/mL) of the plant extracts. Cellular responses were measured using the alamarBlue® assay and the CyQUANT® assay. Plant extracts in the aqueous phase were prepared by boiling whole leaves in water and taking aqueous phase samples at various (1, 2 , 5 minutes boiling) time points. Plant leaves were either added before the water was boiled (cold boiled) or after the water was boiled (hot boiled). The final concentrations of the aqueous plant extracts were 3.3 ng/mL (± 0.3 ng/mL) per sample. The antimicrobial properties of the plant extracts were tested using the well diffusion assay method against Staphylococcus aureus, Klebsiella pnuemoniae and methicillin resistant S. aureus and Bacillus cereus. Results Assay results from the almarBlue® and CYQUANT® assays indicated that extracts from both native plants at various time points (0, 24 and 48 hours) and concentrations (31.25 mg/mL, 62.5 mg/mL, and 125 mg/mL) were significantly higher (n=3, p=0.03 for Kc269, p=0.04 for Kc274, p=0.02 for Fib274, p=0.04 for Kc275 and p=0.001 for Kc276) compared with the untreated controls. Neither plant extract demonstrated cytotoxic effects. Significant antimicrobial activity against methicillin resistant Staphylococcus aureus (p=0.0009 for hot boiled plant A, n=2, p=0.034 for cold boiled plant A, n=2) K. pnuemoniae (p=0.0009 for hot boiled plant A, n=2, p=0.002 for cold boiled plant A, n=2) and B. cereus (p=0.0009 for hot boiled plant A, n=2, p=0.003 for cold boiled plant A, n=2) was observed at concentrations of 3.2 ng/mL for plant A and 3.4 ng/mL for plant B. Conclusion Both native plants contain bioactive compounds that increase cellular metabolic rates and total nucleic acid content. Neither plant was shown to be cytotoxic. Furthermore, both exhibited significant antimicrobial activity.