Amelogenin an extracellular matrix protein in the treatment of venous leg ulcers and other hard to heal wounds. experimental and clinical evidence

Abstract: Amelogenins are extracellular matrix proteins that, under physiological conditions, self-assemble into globular aggregates up to micron-sizes. Studies with periodontal fibroblasts indicate that attachment to these structures increases the endogenous secretion of multiple growth factors and cell proliferation. Pre-clinical and clinical studies indicate that cutaneous wounds benefit from treatment with amelogenins. A randomized controlled trial (RCT) involving patients with hard-to-heal venous leg ulcers (VLUs) (ie, ulcers with a surface area ≥10 cm2 and duration of ≥6 months) showed that the application of amelogenin (Xelma®, Molnlycke Health Care, Gothenburg, Sweden) as an adjunct treatment to compression results in significant reduction in ulcer size, improvement in the state of ulcers, reduced pain, and a larger proportion of ulcers with low levels of exudate, compared with treatment with compression alone. Amelogenin therapy was also shown to be safe to use in that there were no significant differences in adverse events noted between patients treated with amelogenin plus compression and those treated with compression alone. Case study evaluations indicate that the benefits of amelogenin therapy demonstrated in the RCT are being repeated in “real life” situations and that amelogenin therapy may also have a role to play in the treatment of other wound types such as diabetic foot ulcers

Autolysis: mechanisms of action in the removal of devitalised tissue

Chronic wounds affect millions of people worldwide. In the UK alone, the cost of their treatment is estimated to be between £4.5bn and £5.1bn. The implementation of wound-bed preparation strategies remove the barriers to healing and wound debridement is a key component in preparing the wound bed for wound progression. This article aims to review one of the several debridement methods available to clinicians: autolytic debridement. Autolysis (i.e. autolytic debridement) uses the body's own enzymatic mechanisms to remove devitalised tissue in order to remove the barriers to healing. This review aims to provide clinicians working in wound care with a better understanding of the mechanisms and implications of autolytic debridement

The Role of Resilience in Rebuilding Lives of Injured Veterans

The aim of this commentary is to discuss potential clinical implications of introducing resilience building interventions into care for veterans who are living with a war wound. Some war veterans are expected to live with a wound upon discharge from an active military role and also to fit into civilian life. These lifestyle adjustments can tax the person’s coping abilities and in that context may hinder successful adaptation. The experience of living with a wound or wounds, either acute or chronic, is connected to losses, including loss of mobility, loss of financial capacity (unable to work during some of the wound healing period) and losses attached to changed social roles. Psychological stress is also a common experience for veterans returning to civilian life. Psychological stress is associated with impaired healing or dysregulation of a biomarker associated with wound healing. Modern health practice is centred on symptom reduction and working with pathology however, working with people’s adaptive behaviours such as resilience has not been a consideration. Using the resilience model as a conceptual framework healthcare professionals can engage with veterans towards resilience within the context of their personal experience of ill health. Using this contemporary framework for considering these aspects of care has the potential to facilitate resistance to stressors associated with being injured potentially averting quality of life impairments

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

<p>Abstract</p> <p>Background</p> <p>The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression.</p> <p>Methods/Design</p> <p>The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm²or >10 cm². Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process.</p> <p>Discussion</p> <p>The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes.</p> <p>Trial Registration</p> <p>ACTRN12608000599370</p

One-Step Purification of Recombinant Human Amelogenin and Use of Amelogenin as a Fusion Partner

Amelogenin is an extracellular protein first identified as a matrix component important for formation of dental enamel during tooth development. Lately, amelogenin has also been found to have positive effects on clinical important areas, such as treatment of periodontal defects, wound healing, and bone regeneration. Here we present a simple method for purification of recombinant human amelogenin expressed in Escherichia coli, based on the solubility properties of amelogenin. The method combines cell lysis with recovery/purification of the protein and generates a >95% pure amelogenin in one step using intact harvested cells as starting material. By using amelogenin as a fusion partner we could further demonstrate that the same method also be can explored to purify other target proteins/peptides in an effective manner. For instance, a fusion between the clinically used protein PTH (parathyroid hormone) and amelogenin was successfully expressed and purified, and the amelogenin part could be removed from PTH by using a site-specific protease

Aspirin versus placebo for the treatment of Venous Leg Ulcers – a phase II, pilot, randomised trial (AVURT).

Background Venous leg ulcers (VLUs) can take many months to heal and 25% fail to heal. The main treatment for venous leg ulcers is compression therapy and few additional therapies exist. Two previous trials indicated that low-dose aspirin may improve healing time, but these trials were insufficiently robust. Methods A multi-centred, pilot, phase II, randomised, double blind, parallel-group, placebo-controlled, efficacy trial (RCT) was conducted to determine: if aspirin improves VLU healing time; the safety of aspirin in this population; treatment compliance; and the feasibility of recruitment to a phase III trial. We recruited patients from secondary care who were aged ≥ 18 years, had a chronic VLU and not regularly taking aspirin. Participants were randomly assigned (1:1) to receive 300 mg of daily aspirin or placebo in addition to standard care, which consisted of multi component compression therapy aiming to deliver 40 mmHg at the ankle where possible. The randomisation list was stratified by ulcer size (≤ 5 cm2 or > 5 cm2). The primary endpoint was time to ulcer healing, which was defined as ‘complete epithelial healing in the absence of scab (eschar) with no dressing required’. Safety outcomes were assessed in all participants who received at least one dose of the study drug. Results Twenty-seven patients were recruited from eight sites (target 100 patients). A short time-frame to recruit and a large number of patients failing to meet the eligibility criteria were the main barriers to recruitment. There was no evidence of a difference in time to healing of the reference ulcer following adjustment for log ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected serious adverse event related to aspirin was recorded. A number of options to improve recruitment were explored. Conclusions There was no evidence that aspirin was effective in expediting the healing of chronic VLUs. However, the analysis was underpowered due to the low number of participants recruited. The trial design would require substantial amendment in order to progress to a phase III (effectiveness) trial