A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing

The aim of this study was to observe both the clinical signs and symptoms of wounds at risk of infection, that is critically colonised (biofilm infected) and antimicrobial‐performance of an ionic silver alginate/carboxymethylcellulose (SACMC) dressing, in comparison with a non silver calcium alginate fibre (AF) dressing, on chronic venous leg and pressure ulcers. Thirty‐six patients with venous or pressure ulcers, considered clinically to be critically colonised (biofilm infected), were randomly chosen to receive either an SACMC dressing or a non silver calcium AF dressing. The efficacy of each wound dressing was evaluated over a 4‐week period. The primary study endpoints were prevention of infection and progression to wound healing. The SACMC group showed a statistically significant (P = 0·017) improvement to healing as indicated by a reduction in the surface area of the wound, over the 4‐week study period, compared with AF controls. In conclusion, the SACMC dressing showed a greater ability to prevent wounds progressing to infection when compared with the AF control dressing. In addition, the results of this study also showed an improvement in wound healing for SACMC when compared with a non silver dressing.     

Peroxide‐based oxygen generating topical wound dressing for enhancing healing of dermal wounds

Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full‐thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds.     

Clinical efficacy of a silver‐releasing foam dressing in venous leg ulcer healing: a randomised controlled trial

Biatain and Biatain‐Ag are two identical wound dressings except the fact that Biatain‐Ag releases silver. In the present multinational double‐blinded randomised controlled trial the effect of the two dressings were compared for treatment of venous leg ulcers. A total of 181 patients were treated for 6 weeks with either Biatain or Biatain‐Ag followed by 4 weeks treatment with Biatain. Biatain‐Ag showed superior performance in relative wound area reduction after 6 weeks treatment and the estimated treatment difference increased after 10 weeks indicating that the effect of silver continues at least for 4 weeks after treatment. A subgroup of the patients differed significantly from the others with respect to parameters associated with a poor healing prognosis; patients were older, had significant history of venous thrombosis, larger ulcers with longer duration and more often recurrent. For this subgroup of patients Biatain‐Ag showed significant (P < 0·05) better performance in terms of relative ulcer area reduction and healing rate. In conclusion, this study suggests the superior performance of Biatain‐Ag compared with the non silver‐releasing dressing Biatain in particular for patients having ulcers associated with a poor healing prognosis.     

The effectiveness of a four‐layer compression bandage system in comparison with Class 3 compression hosiery on healing and quality of life in patients with venous leg ulcers: a randomised controlled trial

An increasing number of compression systems available for treatment of venous leg ulcers and limited evidence on the relative effectiveness of these systems are available. The purpose of this study was to conduct a randomised controlled trial to compare the effectiveness of a four‐layer compression bandage system and Class 3 compression hosiery on healing and quality of life (QL) in patients with venous leg ulcers. Data were collected from 103 participants on demographics, health, ulcer status, treatments, pain, depression and QL for 24 weeks. After 24 weeks, 86% of the four‐layer bandage group and 77% of the hosiery group were healed (P = 0·24). Median time to healing for the bandage group was 10 weeks, in comparison with 14 weeks for the hosiery group (P = 0·018). The Cox proportional hazards regression found participants in the four‐layer system were 2·1 times (95% CI 1·2–3·5) more likely to heal than those in hosiery, while longer ulcer duration, larger ulcer area and higher depression scores significantly delayed healing. No differences between groups were found in QL or pain measures. Findings indicate that these systems were equally effective in healing patients by 24 weeks; however, a four‐layer system may produce a more rapid response.     

A randomised controlled 8-week crossover clinical evaluation of the 3M Coban 2 Layer Compression System versus Profore to evaluate the product performance in patients with venous leg ulcers

This study compared a two-layer (Coban 2 Layer) and a four-layer (Profore) compression bandage system in venous leg ulcer patients. Participants (n = 81) were enrolled into an 8-week, randomised, open-label, ten-centre, crossover clinical trial. The primary endpoint was bandage slippage measured at each dressing change. Secondary endpoints included wound healing, health-related quality of life (HRQoL) and patient preference. Mean slippage estimated from a mixed analysis of variance model (697 visits) was 2.48 cm for the two-layer system and 4.17 cm for the four-layer system (P < 0.001). There were no significant differences in percent of wounds that healed (Fisher's exact test, P = 0.30), in wound area reduction (Wilcoxon rank-sum test, P = 0.88) or in linear healing rate (Wilcoxon rank-sum test, P = 0.94). The HRQoL Physical Symptoms and Daily Living scores were significantly higher with the two-layer system (pooled two-sample t-test, P < 0.05). Patients had a strong preference for the two-layer system (72%) than the four-layer system (22%), with 6% having no preference. In conclusion, the two-layer system exhibited significantly less bandage slippage than the four-layer system. While less bandage slippage did not appear to impact wound healing, there was indication that it may have influenced patient preference in favour of the two-layer system and potentially impacted patients' HRQoL.     

Venous leg ulcers: patient concordance with compression therapy and its impact on healing and prevention of recurrence

This study aimed to review available data on the reasons attributed to patient non concordance with compression therapy for the treatment of venous leg ulcers (VLUs), the frequency of non concordance and its effects on clinical outcomes. The biomedical literature was searched for publications on VLUs, compression therapy and concordance over the past 20 years. Physical, aesthetic and cosmetic factors, patient lack of education about VLUs, cost of therapy and issues with treatment by clinicians were all reported to influence concordance with compression therapy. The search identified 10 studies reporting patient concordance with compression stockings or bandages; while non concordance ranged from 2% to 42% of patients in three randomised controlled trials, it was generally higher in real‐world studies, ranging from 9.7% to 80%. Another set of six studies indicated that the healing rate was half and the median time to complete healing was twice as long when patients were not concordant. Further, recurrence rates were 2–20 times greater when patients did not comply with the use of stockings following VLU healing. In conclusion, published biomedical literature has documented that non concordance with compression therapy negatively impacts the outcome of VLUs, highlighting the need to improve patient concordance to maximise therapeutic benefits.     

Safety and performance evaluation of a next‐generation antimicrobial dressing in patients with chronic venous leg ulcers

The objective of this study was to investigate the safety and performance of AQUACEL? Ag+ dressing, a wound dressing containing a combination of anti‐biofilm and antimicrobial agents, in the management of chronic wounds. Patients (n = 42) with venous leg ulcers exhibiting signs of clinical infection were treated for 4 weeks with AQUACEL? Ag+ dressing, followed by management with AQUACEL? wound dressings for 4 weeks. Wound progression, wound size, ulcer pain and clinical evolution of the wound were assessed for up to 8 weeks. Adverse events were recorded throughout the study. AQUACEL? Ag+ dressing had an acceptable safety profile, with only one patient discontinuing from the study, because of a non‐treatment‐related adverse event. After 8 weeks, substantial wound improvements were observed: 5 patients (11·9%) had healed ulcers and 32 patients (76·2%) showed improvement in ulcer condition. The mean ulcer size had reduced by 54·5%. Patients reported less pain as the study progressed. Notable improvements were observed in patients with ulcers that were considered to require treatment with systemic antibiotics or topical antimicrobials at baseline (n = 10), with a mean 70·2% reduction in wound area. These data indicate that AQUACEL? Ag+ dressing has an acceptable safety profile in the management of venous leg ulcers that may be impeded by biofilm.     

Adalimumab treatment leads to reduction of tissue tumor necrosis factor‐alpha correlated with venous leg ulcer improvement: a pilot study

Venous leg ulcers (VLUs) have higher tumor necrosis factor‐α (TNF‐α) levels compared with normal skin. Refractory VLUs of long duration have higher TNF‐α levels compared with VLUs of shorter duration. As up to 75% of VLUs fail to heal with standard care, we sought to evaluate the role of anti‐TNF‐α therapy for patients with refractory VLUs. Evaluable data were obtained in four of five subjects with recalcitrant VLUs treated with 80 mg of subcutaneous adalimumab at week 0 and with 40 mg at week 2 along with compression therapy and were followed‐up for 6 weeks. Wound biopsies taken at weeks 0 and 4 were stained with anti‐TNF‐α antibodies. Average 4‐week percent wound size reduction was 20.5% ± 6.4%. Two patients had wound size reduction more than 25%, and their percent wound size reduction correlated to percent TNF‐α staining score reductions (P = 0.02, R² = 0.999). VLU TNF‐α level decrease 4 weeks post‐adalimumab treatment correlated with wound healing.     

Controlled trial of occlusive dressings in healing chronic venous ulcers

Fifty-six patients with chronic venous ulcers present for a mean of 2.4 years were randomized to either a new occlusive hydrocolloid dressing (Granuflex, Squibb Surgicare) or a porous non-adherent dressing (N A, Johnson and Johnson). In all patients, dressings were applied beneath a standard graduated compression bandage. There was no difference between the two groups, with complete healing in 21 out of 28 (75 per cent) of occlusive dressing patients and 22 out of 28 (78 per cent) with N A dressings by 12 weeks. Careful graduated compression bandaging achieves healing even in the majority of so-called resistant chronic venous ulcers; there was no additional benefit from applying occlusive dressings which tend to be expensive.     

Wound-healing trajectories as outcome measures of venous stasis ulcer treatment

Outcome measures of venous ulcer healing are not uniformly accepted. Stringent criteria of 100% closure fail to provide information of healing over the entire span of repair. Wound-healing trajectories (plot of percentage of wound closure versus time of wound treatment) were constructed for 232 patients treated in eight clinical trials at two independent wound care/research centres. Trajectories were constructed for ulcers that totally healed (100% closure) and those that did not (<100% closure) over a 20-week period. Kaplan-Meier survival plots determined the percentage of patients achieving total healing versus time of treatment. The wound-healing trajectories were almost identical for patients achieving complete ulcer healing, as were the trajectories for patients with less than 100% closure. The trajectories for the ulcers healing completely were significantly different from those with <100% closure. Only 60% of all patients achieved 100% closure by 20 weeks. Using linear regression, it was predicted that it would take 31 weeks for all patients to achieve total healing. Total healing is an inadequate outcome measure for healing of venous stasis ulcers. Clinical trials using this measure would require excessive time periods. As wound-healing trajectories for patients treated at two centres mimic one another, shifting the wound-healing trajectory from one of impaired healing to one of a more ideal healing course may be considered a better outcome measure for determining healing of venous stasis ulcers.     

Efficacy and cost‐effectiveness of octenidine wound gel in the treatment of chronic venous leg ulcers in comparison to modern wound dressings

The aim of this study was to determine the efficacy, safety and cost‐effectiveness of an octenidine‐based wound gel in the treatment of chronic venous leg ulcers. For this purpose, 49 wounds were treated with either modern wound‐phase‐adapted dressings alone (treatment arm 1; n = 17), octenidine wound gel plus modern wound‐phase‐adapted dressings (treatment arm 2; n = 17) or octenidine wound gel alone (treatment arm 3; n = 15). During the study period of 42 days with dressing changes every 3–5 days, wound healing characteristics and treatment costs of different dressings were analysed. Wound size reduction was significantly better (P = 0·028) in both octenidine wound gel treatment arms compared to modern dressings alone with total reductions of 14·6%, 64·1% and 96·2% in treatment arms 1–3. Early wound healing was merely observed under octenidine wound gel treatment (n = 9), whereby lowest treatment costs were generated by octenidine wound gel alone (€20·34/dressing change). As a result, the octenidine wound gel is cost‐effective and well suitable for the treatment of chronic venous leg ulcers, considering both safety and promotion of wound healing.     

A prospective,multicentre, randomised controlled study of human fibroblast‐derived dermal substitute (Dermagraft) in patients with venous leg ulcers

This was an open‐label, prospective, multicentre, randomised controlled study to evaluate the efficacy and safety of human fibroblast‐derived dermal substitute (HFDS) plus four‐layer compression therapy compared with compression therapy alone in the treatment of venous leg ulcers. The primary outcome variable was the proportion of patients with completely healed study ulcers by 12 weeks. The number healed was further summarised by ulcer duration and baseline ulcer size. Sixty‐four (34%) of 186 patients in the HFDS group experienced healing by week 12 compared with 56 (31%) of 180 patients in the control group (P = 0·235). For ulcers ≤ 12 months duration, 49 (52%) of 94 patients in the HFDS group versus 36 (37%) of 97 patients in the control group healed at 12 weeks (P = 0·029). For ulcers ≤ 10 cm², complete healing at week 12 was observed in 55 (47%) of 117 patients in the HFDS group compared with 47 (39%) of 120 patients in the control group (P = 0·223). The most common adverse events (AEs) were wound infection, cellulitis and skin ulcer. The frequency of AEs did not markedly differ between the treatment and control groups.     

A pilot multi‐centre prospective randomised controlled trial of RECELL for the treatment of venous leg ulcers

Venous leg ulcers (VLUs) have a significant impact on approximately 3% of the adult population worldwide, with a mean NHS wound care cost of £7600 per VLU over 12 months. The standard care for VLUs is compression therapy, with a significant number of ulcers failing to heal with this treatment, especially with wound size being a risk factor for non‐healing. This multicentre, prospective, randomised trial evaluated the safety and effectiveness of autologous skin cell suspension (ASCS) combined with compression therapy compared with standard compression alone (Control) for the treatment of VLUs. Incidence of complete wound closure at 14 weeks, donor site closure, pain, Health‐Related Quality of Life (HRQoL), satisfaction, and safety were assessed in 52 patients. At Week 14, VLUs treated with ASCS + compression had a statistically greater decrease in ulcer area compared with the Control (8.94 cm² versus 1.23 cm², P = .0143). This finding was largely driven by ulcers >10 to 80 cm² in size, as these ulcers had a higher mean percentage of reepithelialization at 14 weeks (ASCS + compression: 69.97% and Control: 11.07%, P = .0480). Additionally, subjects treated with ASCS + compression experienced a decrease in pain and an increase in HRQoL compared with the Control. This study indicates that application of ASCS + compression accelerates healing in large venous ulcers.     

A closer examination of atraumatic dressings for optimal healing

The concept that undisturbed wound healing, optimised by dressing choice, improves wound outcomes has become a focal point of consideration when evaluating wound management regimens in recent years. However, little evidence exists related to wound contact layers and the potential detrimental effects of the intimate contact with the wound bed. The aim of this study was to evaluate the effects of atraumatic wound contact dressings on the healing of partial‐thickness wounds in comparison to untreated air‐exposed wounds. Using an in vivo porcine wound model the handling properties of each dressing in terms of adhesion were analysed. Methods of wound characterisation included histological analysis of granulation tissue formation and epithelialisation and this was correlated with various clinical observations. Differences were found between dressings in terms of adherence to the wound bed and surrounding skin, capacity to retain wound exudates and enhancement of healing.     

Randomized clinical trial of three‐layer tubular bandaging system for venous leg ulcers

The safety and efficacy of three‐layer (3L) tubular bandaging as a treatment for venous ulcer healing has not been evaluated despite its use in many clinical settings to treat people with venous leg ulcers. We evaluated the safety and efficacy of 3L tubular bandage compared with short‐stretch compression bandage to heal venous ulcers in a multicenter, open‐label, parallel‐group, randomized controlled trial. We randomized 45 patients with venous leg ulcers of up to 20 cm² area and an ankle brachial pressure index of >0.8 from hospital outpatient wound clinics in Victoria and Queensland, Australia. We measured time to healing and percentage reduction of wound size from baseline to week 12. Secondary outcomes were proportion of ulcers healed, self‐reported compliance of compression bandage, and health‐related quality of life, costs, recurrence rates, and adverse events. A total of 27 ulcers healed, the proportion of healed ulcers was higher for the 3L group (17/23 [74%] vs. 10/22 [46%]) (p = 0.05). Reported bandage tolerance at all treatment visits was 21 (91%) in 3L group vs. 17 (73%) (p = 0.10). There was no difference between the groups in adverse events. Costs were substantially less in 3L group.     

A single‐arm trial indirect comparison investigation: a proof‐of‐concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof‐of‐concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score‐matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi‐layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow‐up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan–Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ² 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non‐healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison.     

Use of customised pressure‐guided elastic bandages to improve efficacy of compression bandaging for venous ulcers

Compression bandaging is a major treatment of chronic venous ulcers. Its efficacy depends on the applied pressure, which is dependent on the skill of the individual applying the bandage. To improve the quality of bandaging by reducing the variability in compression bandage interface pressures, we changed elastic bandages into a customised version by marking them with circular ink stamps, applied when the stretch achieves an interface pressure between 35 and 45 mmHg. Repeated applications by 20 residents of the customised bandage and non‐marked bandage to one smaller and one larger leg were evaluated by measuring the sub‐bandage pressure. The results demonstrated that the target pressure range is more often attained with the customised bandage compared with the non‐marked bandage. The customised bandage improved the efficacy of compression bandaging for venous ulcers, with optimal sub‐bandage pressure.     

Adaptive compression therapy for venous leg ulcers: a clinically effective,patient‐centred approach

A prospective, randomised, 12‐week study was performed to evaluate the efficacy and tolerability of two compression methods for venous leg ulcers (VLUs); a new adaptive compression therapy (ACT) system, combining intermittent and sustained pneumatic compression (n = 38) and a conventional four‐layer bandage system (n = 52). Primary outcomes were ulcer healing and safety. Secondary outcomes were comfort, compliance, ulcer pain, patient‐perceived product performance and quality of life. Ulcer healing rate was similar (31·6% versus 42·3%, respectively, P = 0·30) between the treatments. Adverse events and patient‐rated comfort were also similar. Average daily usage for the dual system was 10·5 and 1·8 hours in the sustained and intermittent modes, respectively, representing its use during 71% of waking hours. Predicted final ulcer pain was also similar (P = 0·68). Performance was subjectively better for adaptive compression and significantly higher for exudate management (P = 0·04), skin protection (P < 0·001), removal ease (P = 0·0007), bathing (P < 0·0001) and sleep comfort (P = 0·0405). The adjusted final quality‐of‐life score was 0·1025 higher for adaptive compression (P = 0·0375). Subjects with healed ulcers attained higher final scores than unhealed subjects (P = 0·0004). This study provides evidence that ACT is comparably efficacious to successfully heal VLUs compared with four‐layer bandage management but is better accepted and achieves higher patient‐reported quality‐of‐life scores in these challenging patients.     

The effect of a new wound dressing on wound healing: Biochemical and histopathological evaluation

Electrospinning process has gained importance in the production of wound dressings in recent years. The wound dressings prepared by electrospinning method provide many advantages over conventional wound dressings. The aim of this study was to assess the histological, biochemical, and immunohistochemical evaluation of collagen/doxycycline loaded nanofiber wound dressing in both acute and chronic wound healing. Full-thickness wound model was created on rats and rats were divided in two main groups: normoglycemic (acute) and hyperglycemic (chronic) groups. Each group was divided into three sub groups: not treated (control) group, treated with nanofiber wound dressing group and treated with commercial product group. Wound closure rates were measured. Oxidative events were investigated by biochemical analyses. In addition to histological studies, matrix metalloproteinase, tissue inhibitor of metalloproteinase, vascular endothelial growth factor, basic-fibroblast growth factor, and von Willebrand factor levels were investigated with immunohistochemical studies. According to the biochemical analyses, it was concluded that the nanofiber wound dressing helps to increase antioxidant capacity and decrease lipid peroxidation. Immunohistochemical studies showed that nanofiber wound dressing enhanced angiogenesis and shortened the inflammatory phase. It was concluded that an effective and safe prototype nanofiber wound dressing, which has similar wound healing effect to the commercial product, has been developed to be used in acute or chronic wound treatment.     

OASIS wound matrix versus Hyaloskin in the treatment of difficult-to-heal wounds of mixed arterial/venous aetiology

Mixed arterial/venous (A/V) ulcers are difficult to treat and slow to heal likely as a result of deficiencies in molecular and cellular elements in the wound bed. Recently, biomaterials have been developed that replace extracellular matrix (ECM) molecules and growth factors critical to the normal healing process. In this study, the effects of OASIS and Hyaloskin were evaluated to compare the effectiveness of these two ECM-based products in their ability to achieve complete wound healing of mixed A/V ulcers. After 16 weeks of treatment, patients in each group were evaluated on four criteria: complete wound healing, time to dressing change, pain and comfort. Complete wound closure was achieved in 82.6% of OASIS-treated ulcers compared with 46.2% of Hyaloskin-treated ulcers (P < 0.001). Statistically significant differences favouring the OASIS treatment group were also reported for time to dressing change (P < 0.05), pain (P < 0.05) and patient comfort (P < 0.01). Overall, OASIS was superior to Hyaloskin for the treatment of patients with mixed A/V ulcers, a population in which standard treatment options largely consist of moist wound dressings and compression therapy is typically not an option. OASIS is a useful and well-tolerated treatment for mixed A/V ulcers that has the potential to improve quality of life and reduce costs associated with standard of care.