Efficacy of a topical concentrated surfactant gel on microbial communities in non‐healing diabetic foot ulcers with chronic biofilm infections: A proof‐of‐concept study

This proof‐of‐concept study sought to determine the effects of standard of care (SOC) and a topically applied concentrated surfactant gel (SG) on the total microbial load, community composition, and community diversity in non‐healing diabetic foot ulcers (DFUs) with chronic biofilm infections. SOC was provided in addition to a topical concentrated SG, applied every 2 days for 6 weeks. Wound swabs were obtained from the base of ulcers at baseline (week 0), week 1, mid‐point (week 3), and end of treatment (week 6). DNA sequencing and real‐time quantitative polymerase chain reaction (qPCR) were employed to determine the total microbial load, community composition, and diversity of patient samples. Tissue specimens were obtained at baseline and scanning electron microscopy and peptide nucleic acid fluorescent in situ hybridisation with confocal laser scanning microscopy were used to confirm the presence of biofilm in all 10 DFUs with suspected chronic biofilm infections. The application of SG resulted in 7 of 10 samples achieving a reduction in mean log10 total microbial load from baseline to end of treatment (0.8 Log10 16S copies, ±0.6), and 3 of 10 samples demonstrated an increase in mean Log10 total microbial load (0.6 log10 16S copies, ±0.8) from baseline to end of treatment. Composition changes in microbial communities were driven by changes to the most dominant bacteria. Corynebacterium sp. and Streptococcus sp. frequently reduced in relative abundance in patient samples from week 0 to week 6 but did not disappear. In contrast, Staphylococcus sp., Finegoldia sp., and Fusobacterium sp., relative abundances frequently increased in patient samples from week 0 to week 6. The application of a concentrated SG resulted in varying shifts to diversity (increase or decrease) between week 0 and week 6 samples at the individual patient level. Any shifts in community diversity were independent to changes in the total microbial loads. SOC and a topical concentrated SG directly affect the microbial loads and community composition of DFUs with chronic biofilm infections.     

Allogeneic keratinocyte for intractable chronic diabetic foot ulcers: A prospective observational study

Chronic diabetic foot ulcers (DFUs) are a common problem in patients with diabetes and are often difficult to treat. The application of newly developed dressing material in patients with chronic DFUs has been reported to be effective. The purpose of this study was to evaluate the usefulness of allogeneic keratinocyte treatment for chronic DFUs. We performed weekly allogeneic keratinocyte treatment for up to 12 weeks in 71 patients with intractable DFUs. We investigated healing rate, wound‐healing velocity, and time to 50% wound size reduction and analysed factors affecting ulcer healing. Fifty‐six patients (78.8%) had complete wound healing. Forty‐six patients (64.7%) showed complete healing within an average of 6.1 weeks, and 10 patients (14.1%) showed partial healing with an average 35.5% reduction vs initial size at the end of follow up. The 10 patients who showed partial healing continued to receive treatment after the 12‐week study period. The mean time to complete wound healing was 7.8 weeks. Fifteen patients (21.1%) experienced treatment failure because of infection, local necrosis, no change in ulcer size, or osteomyelitis during the follow‐up period. No adverse events were observed. Allogeneic keratinocyte treatment is effective for chronic, difficult‐to‐treat DFUs.     

Autologous platelet‐rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective,randomized clinical trial

The purpose of the study is to examine the safety and effectiveness of topical autologous platelet‐rich gel (APG) application on facilitating the healing of diabetic chronic refractory cutaneous ulcers. The study was designed as a prospective, randomized controlled trial between January 1, 2007 and December 31, 2011. Eligible inpatients at the Diabetic Foot Care Center of West China Hospital, Sichuan University (China) were randomly prescribed with a 12‐week standard treatment of ulcers (the control group) or standard treatment plus topical application APG (the APG group). The wound healing grades (primary endpoint), time to complete healing, and healing velocity within 12 weeks were monitored as short‐term effectiveness measurements, while side effects were documented safety endpoints. The rates of survival and recurrence within the follow up were recorded as long‐term effectiveness endpoints. Analysis on total diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers (DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was statistically more effective than standard treatment (p < 0.05 in both total DUs and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%) in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58 (69.0%) and 37/55 (67.3%) in the control group from intent to treat population. The Kaplan‐Meier time‐to‐healing were significantly different between the two groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were identified after topical APG application. The long‐term survival and recurrence rates were comparative between groups (p > 0.05). This study shows that topical APG application plus standard treatment is safe and quite effective on diabetic chronic refractory cutaneous ulcers, compared with standard treatment.     

Topical administration of a connexin43‐based peptide augments healing of chronic neuropathic diabetic foot ulcers: A multicenter,randomized trial

Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap‐junctional protein connexin43 (Cx43) has roles in dermal wound healing and targeting Cx43 signalling accelerates wound reepithelialization. In a prospective, randomized, multicenter clinical trial we evaluated the efficacy and safety of a peptide mimetic of the C‐terminus of Cx43, alpha connexin carboxy‐terminal (ACT1), in accelerating the healing of chronic diabetic foot ulcers (DFUs) when incorporated into standard of care (SOC) protocols. Adults with DFUs of at least four weeks duration were randomized to receive SOC with or without topical application of ACT1. Primary outcome was mean percent ulcer reepithelialization and safety variables included incidence of treatment related adverse events (AEs) and detection of ACT1 immunogenicity. ACT1 treatment was associated with a significantly greater reduction in mean percent ulcer area from baseline to 12 weeks (72.1% vs. 57.1%; p = 0.03). Analysis of incidence and median time‐to‐complete‐ulcer closure revealed that ACT1 treatment was associated with a greater percentage of participants that reached 100% ulcer reepitheliazation and a reduced median time‐to‐complete‐ulcer closure. No AEs reported were treatment related, and ACT1 was not immunogenic. Treatment protocols that incorporate ACT1 may present a therapeutic strategy that safely augments the reepithelialization of chronic DFUs.     

Microscopy visualisation confirms multi‐species biofilms are ubiquitous in diabetic foot ulcers

Increasing evidence within the literature has identified the presence of biofilms in chronic wounds and proposed that they contribute to delayed wound healing. This research aimed to investigate the presence of biofilm in diabetic foot ulcers (DFUs) using microscopy and molecular approaches and define if these are predominantly mono‐ or multi‐species. Secondary objectives were to correlate wound observations against microscopy results in ascertaining if clinical cues are useful in detecting wound biofilm. DFU tissue specimens were obtained from 65 subjects. Scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridisation (PNA‐FISH) techniques with confocal laser scanning microscopy (CLSM) were used to visualise biofilm structures. Next‐generation DNA sequencing was performed to explore the microbial diversity. Clinical cues that included the presence of slough, excessive exudate, a gel material on the wound bed that reforms quickly following debridement, poor granulation and pyocyanin were correlated to microscopy results. Of the 65 DFU specimens evaluated by microscopy, all were characterised as containing biofilm (100%, P < 0·001). The presence of both mono‐species and multi‐species biofilms within the same tissue sections were detected, even when DNA sequencing analysis of DFU specimens revealed diverse polymicrobial communities. No clinical correlations were identified to aid clinicians in identifying wound biofilm. Microscopy visualisation, when combined with molecular approaches, confirms biofilms are ubiquitous in DFUs and form either mono‐ or multi‐species biofilms. Clinical cues to aid clinicians in detecting wound biofilm are not accurate for use in DFUs. A paradigm shift of managing DFUs needs to consider anti‐biofilm strategies.     

The efficacy of topical royal jelly on healing of diabetic foot ulcers: a double‐blind placebo‐controlled clinical trial

Foot ulcers are major sources of morbidity in individuals with diabetes mellitus. As royal jelly (RJ, a worker honey bee product) contains enzymatic, antibacterial and vasodilative properties, it can potentially help in healing of diabetic foot ulcers (DFUs). This study aimed to evaluate the efficacy of topical RJ on healing of DFUs. Diabetic patients with foot ulcers who were referred to us at Khorshid Hospital, Isfahan, Iran, were managed by offloading, infection control, vascular improvement and debridement (if required). Then, all ulcers were randomly selected to receive either 5% sterile topical RJ or placebo on their total surface area. Patients were followed for 3 months or until complete healing. Twenty‐five patients (6 females and 19 males) and a total of 64 ulcers were included and randomly allocated to case or control group (32 per group). Four ulcers were excluded and 60 ulcers included in the final analysis. Healing parameters including depth, length and width reduction rate, duration of complete healing and incidence of complete healing did not show any significant difference (P = 0·69, 0·95, 0·7, 0·74 and 0·6, respectively) between groups. We did not observe any side effect of topical RJ application. This study could not confirm any significant superiority of 5% topical RJ over placebo for the treatment of DFUs.     

Serial surgical debridement: A retrospective study on clinical outcomes in chronic lower extremity wounds

This investigation was conducted to determine if a correlation exists between wound healing outcomes and serial debridement in chronic venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). We retrospectively analyzed the results from two controlled, prospective, randomized pivotal trials of topical wound treatments on 366 VLUs and 310 DFUs over 12 weeks. Weekly wound surface area changes following debridement and 12-week wound closure rates between centers and patients were evaluated. VLUs had a significantly higher median wound surface area reduction following clinical visits with surgical debridement as compared with clinical visits with no surgical debridement (34%, p =0.019). Centers where patients were debrided more frequently were associated with higher rates of wound closure in both clinical studies ( p =0.007 VLU, p =0.015 DFU). Debridement frequency per patient was not statistically correlated to higher rates of wound closure; however, there was some minor evidence of a positive benefit of serial debridement in DFUs (odds ratio—2.35, p =0.069). Our results suggest that frequent debridement of DFUs and VLUs may increase wound healing rates and rates of closure, though there is not enough evidence to definitively conclude a significant effect. Future clinical research in wound care should focus on the relationship between serial surgical wound debridement and improved wound healing outcomes as demonstrated in this study.     

Complete wound closure following a single topical application of a novel autologous homologous skin construct: first evaluation in an open‐label,single‐arm feasibility study in diabetic foot ulcers

Diabetic foot ulcers (DFUs) are a growing burden on patients and health care systems that often require multiple treatments of both conventional and advanced modalities to achieve complete wound closure. A novel autologous homologous skin construct (AHSC) has been developed to treat cutaneous defects with a single topical application, by leveraging the endogenous repair capabilities of the patient's healthy skin. The AHSC's ability to close DFUs with a single treatment was evaluated in an open‐label, single‐arm feasibility study. Eleven patients with DFUs extending up to tendon, bone, or capsule received a single topical application of AHSC. Closure was documented weekly with high‐resolution digital photography and wound planimetry. All 11 DFUs demonstrated successful graft take. Ten DFUs closed within 8 weeks. The median time‐to‐complete closure was 25 days. The mean percent area reduction for all 11 wounds at 4 weeks was 83%. There were no adverse events related to the AHSC treatment site. This pilot study demonstrated AHSC may be a viable single application topical intervention for DFUs and warrants investigation in larger, controlled studies.     

A pilot study evaluating non‐contact low‐frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers

Non‐contact low‐frequency ultrasound (NCLF‐US) devices have been increasingly used for the treatment of chronic non‐healing wounds. The appropriate dose for NCLF‐US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non‐healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non‐healing DFUs for 5 weeks receiving standard of care and/or NCLF‐US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF‐US thrice per week (Group 1), NCLF‐US once per week (Group 2) and the control (Group 3) that received no NCLF‐US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of pro‐inflammatory cytokines (IL‐6, IL‐8, IL‐1β, TNF‐α and GM‐CSF), matrix metalloproteinase‐9 (MMP‐9), vascular endothelial growth factor (VEGF) and macrophages in response to NCLF‐US consistent with wound reduction, when compared with control group subjects. This proof‐of‐concept pilot study demonstrates that NCLF‐US is effective in treating neuropathic diabetic foot ulcers through, at least in part, inhibiting pro‐inflammatory cytokines in chronic wound and improving tissue regeneration. Therapeutic application of NFLU, thrice (3) per week, renders the best wound area reduction.     

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.     

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.     

The role of surgical debridement in healing of diabetic foot ulcers

A critical question in the treatment of chronic wounds is whether and when debridement is needed. The three most common chronic wounds are the diabetic foot ulcer (DFU), the venous leg ulcer, and the pressure or decubitus ulcer. Surgical debridement, aimed at removing necrotic, devitalized wound bed and wound edge tissue that inhibits healing, is a longstanding standard of care for the treatment of chronic, nonhealing wounds. Debridement encourages healing by converting a chronic nonhealing wound environment into a more responsive acute healing environment. While the rationale for debridement seems logical, the evidence to support its use in enhancing healing is scarce. Currently, there is more evidence in the literature for debridement for DFUs than for venous ulcers and pressure ulcers; however, the studies on which clinicians have based their rationale for debridement in DFUs possess methodologic flaws, small sample sizes, and bias. Thus, further studies are needed to develop clinical evidence for its inclusion in treatment protocols for chronic wounds. Here, the authors review the scientific evidence for debridement of DFUs, the rationale for debridement of DFUs, and the insufficient data supporting debridement for venous ulcers and pressure ulcers.     

Use of 16S rRNA sequencing and quantitative PCR to correlate venous leg ulcer bacterial bioburden dynamics with wound expansion,antibiotic therapy,and healing

Clinical diagnosis of infection in chronic wounds is currently limited to subjective clinical signs and culture‐based methods that underestimate the complexity of wound microbial bioburden as revealed by DNA‐based microbial identification methods. Here, we use 16S rRNA next generation sequencing and quantitative polymerase chain reaction to characterize weekly changes in bacterial load, community structure, and diversity associated with a chronic venous leg ulcer over the 15‐week course of treatment and healing. Our DNA‐based methods and detailed sampling scheme reveal that the bacterial bioburden of the wound is unexpectedly dynamic, including changes in the bacterial load and community structure that correlate with wound expansion, antibiotic therapy, and healing. We demonstrate that these multidimensional changes in bacterial bioburden can be summarized using swabs taken prior to debridement, and therefore, can be more easily collected serially than debridement or biopsy samples. Overall, this case illustrates the importance of detailed clinical indicators and longitudinal sampling to determine the pathogenic significance of chronic wound microbial dynamics and guide best use of antimicrobials for improvement of healing outcomes.     

A multicentre prospective randomised controlled comparative parallel study of dehydrated human umbilical cord (EpiCord) allograft for the treatment of diabetic foot ulcers

The aim of this study was to determine the safety and effectiveness of dehydrated human umbilical cord allograft (EpiCord) compared with alginate wound dressings for the treatment of chronic, non‐healing diabetic foot ulcers (DFU). A multicentre, randomised, controlled, clinical trial was conducted at 11 centres in the United States. Individuals with a confirmed diagnosis of Type 1 or Type 2 diabetes presenting with a 1 to 15 cm² ulcer located below the ankle that had been persisting for at least 30 days were eligible for the 14‐day study run‐in phase. After 14 days of weekly debridement, moist wound therapy, and off‐loading, those with ≤30% wound area reduction post‐debridement (n = 155) were randomised in a 2:1 ratio to receive a weekly application of EpiCord (n = 101) or standardised therapy with alginate wound dressing, non‐adherent silicone dressing, absorbent non‐adhesive hydropolymer secondary dressing, and gauze bandage roll (n = 54). All wounds continued to have appropriate off‐loading during the treatment phase of the study. Study visits were conducted for 12 weeks. At each weekly visit, the DFU was cleaned and debrided as necessary, with the wound photographed pre‐ and post‐debridement and measured before the application of treatment group‐specific dressings. A follow‐up visit was performed at week 16. The primary study end point was the percentage of complete closure of the study ulcer within 12 weeks, as assessed by Silhouette camera. Data for randomised subjects meeting study inclusion criteria were included in an intent‐to‐treat (ITT) analysis. Additional analysis was conducted on a group of subjects (n = 134) who completed the study per protocol (PP) (EpiCord, n = 86, alginate, n = 48) and for those subjects receiving adequate debridement (EpiCord, n = 67, alginate, n = 40). ITT analysis showed that DFUs treated with EpiCord were more likely to heal within 12 weeks than those receiving alginate dressings, 71 of 101 (70%) vs 26 of 54 (48%) for EpiCord and alginate dressings, respectively, P = 0.0089. Healing rates at 12 weeks for subjects treated PP were 70 of 86 (81%) for EpiCord‐treated and 26 of 48 (54%) for alginate‐treated DFUs, P = 0.0013. For those DFUs that received adequate debridement (n = 107, ITT population), 64 of 67 (96%) of the EpiCord‐treated ulcers healed completely within 12 weeks, compared with 26 of 40 (65%) of adequately debrided alginate‐treated ulcers, P < 0.0001. Seventy‐five subjects experienced at least one adverse event, with a total of 160 adverse events recorded. There were no adverse events related to either EpiCord or alginate dressings. These results demonstrate the safety and efficacy of EpiCord as a treatment for non‐healing DFUs.     

A prospective,non comparative,multicenter study to investigate the effect of cadexomer iodine on bioburden load and other wound characteristics in diabetic foot ulcers

Few studies regarding wound treatment with topical antimicrobials evaluate change in the bacterial bioburden of the wound with treatment. This study sought out to determine the in vivo effect of cadexomer iodine antibacterial dressing on diabetic foot ulcers (DFUs) that were infected or achieved a critical level of colonisation, looking specifically at wound progression in relation to bioburden. Fifteen patients corresponding to 16 total DFUs met criteria of displaying clinical signs of infection or critical colonisation and were suitable for a topical antibacterial dressing. They underwent weekly treatment for 6 weeks. Cultures were taken at week 0, 3 and 6 as appropriate. At week 6 median log₁₀ bacterial count reduction of 1.0 was observed from baseline (p = 0·025). At week 3‐ a median log₁₀ bacterial count reduction of 0.3 was observed from baseline (p = 0·049). Over the study period there was a 53.6% median reduction of the wound surface area. There were no patients that completely healed their ulcer over the 6 week study period. There was a statistically significant median reduction in the bacterial load over the 6 week period (p = 0·025) as well as 3 weeks (p = 0·049). This was accompanied by a median reduction of 53.6% in ulcer surface area and 50% in ulcer depth from baseline to final.     

Differentiating diabetic foot ulcers that are unlikely to heal by 12 weeks following achieving 50% percent area reduction at 4 weeks

This retrospective analysis included intent-to-treat control patient data from two published, randomised, diabetic foot ulcer (DFU) trials in an effort to differentiate ulcers that are unlikely to heal by 12 weeks despite early healing progress [≥50% percent area reduction (PAR) at 4 weeks]. Predicted and actual wound area trajectories in DFUs that achieved early healing progress were analysed from weeks 5 to 12 and compared for ulcers that did and did not heal at 12 weeks. In 120 patients who achieved ≥50% PAR by week 4, 62 (52%) failed to heal by 12 weeks. Deviations from the predicted healing course were evident by 6 weeks for non healing ulcers. A 2-week delay in healing significantly lowered healing rates (P = 0·001). For DFUs with ≥50% PAR at 4 weeks, those achieving ≥90% versus <90% PAR at 8 weeks had a 2·7-fold higher healing rate at 12 weeks (P = 0·001). A PAR of <90% at 8 weeks provided a negative predictive value for DFU healing at 12 weeks of 82%. For ulcers that fail to progress or worsen from weeks 4 to 6, and those that fail to achieve 90% PAR at 8 weeks, reevaluation of the wound and its treatment is recommended.     

Early healing rates and wound area measurements are reliable predictors of later complete wound closure

This study was undertaken to determine if healing rates are reliable early predictors of ultimate complete wound closure in venous leg ulcers and diabetic foot wounds. We conducted a retrospective analysis of 306 venous leg ulcers and 241 diabetic foot ulcers enrolled in two large controlled, prospective, randomized pivotal trials to compare topical wound treatments, to determine whether certain early markers of healing could be correlated with later total wound closure. Two-sided tests at 95% confidence demonstrated that wound margin advance, initial healing rate, percent wound surface area reduction, and wound healing trajectories (all p <0.001) were powerful predictors of complete wound healing at 12 weeks. Wounds with poor healing progress by these criteria at 4 weeks were highly likely to remain unhealed after 8 additional weeks of treatment. Analysis of the diabetic foot ulcers and venous leg ulcers subgroups separately demonstrated consistent statistical test results with high significance; similarly, the results remained valid independent of the topical treatment used. The early prediction of eventual wound healing or nonhealing using early healing rates may enable more efficient triage of patients to advanced healing technologies. We believe that these surrogate markers are robust predictors of healing regardless of wound etiology and that they merit wider use in clinical trials and routine patient care.     

A prospective,randomised, controlled,multicentre clinical trial examining healing rates,safety and cost to closure of an acellular reticular allogenic human dermis versus standard of care in the treatment of chronic diabetic foot ulcers

Acellular dermal matrices can successfully heal wounds. This study's goal was to compare clinical outcomes of a novel, open‐structure human reticular acellular dermis matrix (HR‐ADM) to facilitate wound closure in non‐healing diabetic foot ulcers (DFUs) versus DFUs treated with standard of care (SOC). Following a 2‐week screening period in which DFUs were treated with offloading and moist wound care, patients were randomised to either SOC alone or HR‐ADM plus SOC applied weekly for up to 12 weeks. At 6 weeks, the primary outcome time, 65% of the HR‐ADM‐treated DFUs healed (13/20) compared with 5% (1/20) of DFUs that received SOC alone. At 12 weeks, the proportions of DFUs healed were 80% and 20%, respectively. Mean time to heal within 12 weeks was 40 days for the HR‐ADM group compared with 77 days for the SOC group. There was no incidence of increased adverse or serious adverse events between groups or any adverse events related to the graft. Mean and median graft costs to closure per healed wound in the HR‐ADM group were $1475 and $963, respectively. Weekly application of HR‐ADM is an effective intervention for promoting closure of non‐healing DFUs.     

Topical oxygen therapy results in complete wound healing in diabetic foot ulcers

Diabetic foot ulcers (DFUs) are a significant problem in an aging population. Fifteen percent of diabetics develop a DFU over their lifetime, which can lead to potential amputation. The 5‐year survival rate after amputation is 31%, which is greater than the lifetime risk of mortality from cancer. Topical oxygen is a promising technique for the adjunctive therapy of chronic wounds including DFUs, but few controlled studies exist to support its clinical adoption. The aim of this study was to compare a portable topical oxygen delivery system in patients with nonhealing DFUs to standard best practice. Twenty patients were randomized into a topical oxygen group (n = 10), and a nonplacebo control group with regular dressings and standard care (n = 10), and attended the diabetic foot clinic once weekly for 8 weeks. Ulcer surface area over time was analyzed using standardized digital imaging software. DFUs were present without healing for a mean duration of 76 weeks prior to the study. They found a significant difference in healing rate between patients receiving topical oxygen and those receiving standard care. Topical oxygen, therefore, represents a potentially exciting new technology to shorten healing time in patients with nonhealing DFUs. More prospective randomized and powered studies are needed to determine the benefits of topical oxygen, but our current results are very promising.     

Anti-biofilm efficacy of a lactoferrin/xylitol wound hydrogel used in combination with silver wound dressings

With an epidemic increase in obesity combined with an ageing population, chronic wounds such as diabetic foot ulcers, pressure ulcers and venous leg ulcers are an increasing clinical concern. Recent studies have shown that bacterial biofilms are a major contributor to wound bioburden and interfere with the normal wound healing process; therefore, rational design of wound therapies should include analysis of anti‐biofilm characteristics. Studies using the combined treatment of bacterial biofilms with the innate immune molecule lactoferrin and the rare sugar‐alcohol xylitol have demonstrated an antimicrobial capacity against a clinical wound isolate. Studies presented here used a colony‐drip‐flow reactor biofilm model to assess the anti‐biofilm efficacy of a lactoferrin/xylitol hydrogel used in combination with commercially available silver‐based wound dressings. Log reductions in biofilm viability are compared with a commercially available wound hydrogel used in combination with the silver‐based wound dressings. For both a single species biofilm and a dual species biofilm, the lactoferrin/xylitol hydrogel in combination with the silver wound dressing Acticoat? had a statistically significant reduction in biofilm viability relative to the commercially available wound hydrogel. This study also demonstrated a statistical interaction between the lactoferrin/xylitol hydrogel and the silver wound dressing.