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.     

A clinical trial of Integra Template for diabetic foot ulcer treatment

Individuals with diabetes mellitus are at an increased risk of developing a diabetic foot ulcer (DFU). This study evaluated the safety and efficacy of Integra Dermal Regeneration Template (IDRT) for the treatment of nonhealing DFUs. The Foot Ulcer New Dermal Replacement Study was a multicenter, randomized, controlled, parallel group clinical trial conducted under an Investigational Device Exemption. Thirty‐two sites enrolled and randomized 307 subjects with at least one DFU. Consented patients were entered into the 14‐day run‐in phase where they were treated with the standard of care (0.9% sodium chloride gel) plus a secondary dressing and an offloading/protective device. Patients with less than 30% reepithelialization of the study ulcer after the run‐in phase were randomized into the treatment phase. The subjects were randomized to the control treatment group (0.9% sodium chloride gel; n = 153) or the active treatment group (IDRT, n = 154). The treatment phase was 16 weeks or until confirmation of complete wound closure (100% reepithelialization of the wound surface), whichever occurred first. Following the treatment phase, all subjects were followed for 12 weeks. Complete DFU closure during the treatment phase was significantly greater with IDRT treatment (51%) than control treatment (32%; p = 0.001) at sixteen weeks. The median time to complete DFU closure was 43 days for IDRT subjects and 78 days for control subjects in wounds that healed. The rate of wound size reduction was 7.2% per week for IDRT subjects vs. 4.8% per week for control subjects (p = 0.012). For the treatment of chronic DFUs, IDRT treatment decreased the time to complete wound closure, increased the rate of wound closure, improved components of quality of life and had less adverse events compared with the standard of care treatment. IDRT could greatly enhance the treatment of nonhealing DFUs.     

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.     

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.     

A prospective,randomized, controlled clinical trial on the efficacy of a single‐use negative pressure wound therapy system,compared to traditional negative pressure wound therapy in the treatment of chronic ulcers of the lower extremities

Multicenter, phase‐4, randomized, comparative‐efficacy study in patients with VLUs or DFUs comparing for noninferiority the percentage change in target ulcer dimensions (area, depth, and volume) a single‐use negative pressure wound therapy (s‐NPWT) system versus traditional NPWT (t‐NPWT) over a 12‐week treatment period or up to confirmed healing. Baseline values were taken at the randomization visit. Randomized by wound type and size, 164 patients with non‐infected DFUs and VLUs were included. The ITT population was composed of 161 patients (101 with VLUs, 60 with DFUs) and 115 patients completed follow‐up (64 in the s‐NPWT group and 51 in the t‐NPWT group) (PP population). The average age for all patients was 61.5 years, 36.6% were women, and treatment groups were statistically similar at baseline. Primary endpoint analyses on wound area reduction demonstrated statistically significant reduction in favor of s‐NPWT (p = 0.003) for the PP population and for the ITT population (p < 0.001). Changes in wound depth (p = 0.018) and volume (p = 0.013) were also better with s‐NPWT. Faster wound closure was observed with s‐NPWT (Cox Proportional Hazards ratio (0.493 (0.273, 0.891); p = 0.019) in the ITT population. Wound closure occurred in 45% of patients in the s‐NPWT group vs. 22.2% of patients in the t‐NPWT group (p = 0.002). Median estimate of the time to wound closure was 77 days for s‐NPWT. No estimate could be provided for t‐NPWT due to the low number of patients achieving wound closure. Device‐related AEs were more frequent in the t‐NPWT group (41 AEs from 29 patients) than in the s‐NPWT group (16 AEs from 12 patients). The s‐NPWT system met noninferiority and achieved statistical superiority vs. t‐NPWT in terms of wound progression toward healing over the treatment period. When NPWT is being considered for the management of challenging VLUs and DFUs, s‐NPWT should be considered a first choice over other types of NPWT.     

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.     

Thrombin peptide Chrysalin® stimulates healing of diabetic foot ulcers in a placebo-controlled phase I/II study

Thrombin and thrombin peptides play a role in initiating tissue repair. The potential safety and efficacy of TP508 (Chrysalin) treatment of diabetic foot ulcers was evaluated in a 60-subject, prospective, randomized, double-blind, placebo-controlled phase I/II clinical trial. Chrysalin in saline or saline alone was applied topically, twice weekly, to diabetic ulcers with standardized care and offloading. A dose-dependent effect was seen in the per-protocol population where 1 and 10 mug Chrysalin treatment resulted in 45 and 72% more subjects with complete healing than placebo treatment. Chrysalin treatment of foot ulcers more than doubled the incidence of complete healing (p<0.05), increased mean closure rate approximately 80% (p<0.05), and decreased the median time to 100% closure by approximately 40% (p<0.05). Chrysalin treatment of heel ulcers within this population resulted in mean closure rates 165% higher than placebos (p<0.02) and complete healing in 86% (6/7) of ulcers compared with 0% (0/5) of placebo ulcers (p<0.03). Local wound reactions and adverse events (AEs) were equal between groups with no reported drug-related changes in laboratory tests or serious AEs. These results indicate the potential safety and efficacy of Chrysalin for treatment of diabetic foot ulcers.     

A randomized clinical trial of a human acellular dermal matrix demonstrated superior healing rates for chronic diabetic foot ulcers over conventional care and an active acellular dermal matrix comparator

This study compared the efficacy and safety of a human acellular dermal matrix (ADM), D‐ADM, with a conventional care arm and an active comparator human ADM arm, GJ‐ADM, for the treatment of chronic diabetic foot ulcers. The study design was a prospective, randomized controlled trial that enrolled 168 diabetic foot ulcer subjects in 13 centers across 9 states. Subjects in the ADM arms received one application but could receive one additional application of ADM if deemed necessary. Screen failures and early withdrawals left 53 subjects in the D‐ADM arm, 56 in the conventional care arm, and 23 in the GJ‐ADM arm (2:2:1 ratio). Subjects were followed through 24 weeks with major endpoints at Weeks 12, 16, and 24. Single application D‐ADM subjects showed significantly greater wound closure rates than conventional care at all three endpoints while all applications D‐ADM displayed a significantly higher healing rate than conventional care at Week 16 and Week 24. GJ‐ADM did not show a significantly greater healing rate over conventional care at any of these time points. A blinded, third party adjudicator analyzed healing at Week 12 and expressed “strong” agreement (κ = 0.837). Closed ulcers in the single application D‐ADM arm remained healed at a significantly greater rate than the conventional care arm at 4 weeks posttermination (100% vs. 86.7%; p = 0.0435). There was no significant difference between GJ‐ADM and conventional care for healed wounds remaining closed. Single application D‐ADM demonstrated significantly greater average percent wound area reduction than conventional care for Weeks 2–24 while single application GJ‐ADM showed significantly greater wound area reduction over conventional care for Weeks 4–6, 9, and 11–12. D‐ADM demonstrated significantly greater wound healing, larger wound area reduction, and a better capability of keeping healed wounds closed than conventional care in the treatment of chronic DFUs.     

Use of an aseptically processed,dehydrated human amnion and chorion membrane improves likelihood and rate of healing in chronic diabetic foot ulcers: A prospective,randomised, multi‐centre clinical trial in 80 patients

Amnion and chorion allografts have shown great promise in healing diabetic foot ulcers (DFUs). Results from an interim analysis of 40 patients have demonstrated the accelerated healing ability of a novel aseptically processed, dehydrated human amnion and chorion allograft (dHACA). The goal of this study was to report on the full trial results of 80 patients where dHACA was compared with standard of care (SOC) in achieving wound closure in non‐healing DFUs. After a 2‐week screening period, during which patients with DFUs were unsuccessfully treated with SOC, patients were randomised to either SOC alone or SOC with dHACA applied weekly for up to 12 weeks. At 12 weeks, 85% (34/40) of the dHACA‐treated DFUs healed, compared with 33% (13/40) treated with SOC alone. Mean time to heal within 12 weeks was significantly faster for the dHACA‐ treated group compared with SOC, 37 days vs 67 days in the SOC group (P = .000006). Mean number of grafts used per healed wound during the same time period was 4.0, and mean cost of the tissue to heal a DFU was $1771. The authors concluded that aseptically processed dHACA heals DFUs significantly faster than SOC at 12 weeks.     

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.     

Use of a purified reconstituted bilayer matrix in the management of chronic diabetic foot ulcers improves patient outcomes vs standard of care: Results of a prospective randomised controlled multi‐centre clinical trial

Diabetic foot infections continue to be a major challenge for health care delivery systems. Following encouraging results from a pilot study using a novel purified reconstituted bilayer matrix (PRBM) to treat chronic diabetic foot ulcers (DFUs), we designed a prospective, multi‐centre randomised trial comparing outcomes of PRBM at 12 weeks compared with a standard of care (SOC) using a collagen alginate dressing. The primary endpoint was percentage of wounds closed after 12 weeks. Secondary outcomes included assessments of complications, healing time, quality of life, and cost to closure. Forty patients were included in an intent‐to‐treat (ITT) and per‐protocol (PP) analysis, with 39 completing the study protocol (n = 19 PRBM, n = 20 SOC). Wounds treated with PRBM were significantly more likely to close than wounds treated with SOC (ITT: 85% vs 30%, P = .0004, PP: 94% vs 30% P = .00008), healed significantly faster (mean 37 days vs 67 days for SOC, P = .002), and achieved a mean wound area reduction within 12 weeks of 96% vs 8.9% for SOC. No adverse events (AEs) directly related to PRBM treatment were reported. Mean PRBM cost of healing was $1731. Use of PRBM was safe and effective for treatment of chronic DFUs.     

High‐dose folic acid and its effect on early stage diabetic foot ulcer wound healing

High‐dose folic acid (HDFA; vitamin B9)—5 mg, given daily, has not been evaluated as a treatment to improve early stage‐diabetic foot ulcer (ES‐DFU) wound healing. However, HDFA has been demonstrated to correct: (a) endothelial dysfunction and decreased nitric oxide (NO) bioavailability, associated with type‐2 diabetes mellitus (T2DM); and (b) hyperhomocysteinemia (HHcy) that may promote impaired DFU‐wound healing. Measures of wound area (cm²) reduction (wound closure; WC), over a 4‐week period (4 W‐WC), greater than 50% of the wound area, have been reported as a robust indicator of the potential for DFU‐wound healing. By using this model, we examined the effectiveness of a wound treatment in promoting progressive healing and complete wound closure for the chronic, nonhealing DFU‐wound. To investigate this possible relationship between HDFA and ES‐DFU wound healing, a retrospective cohort study of medical records, between November 2018 and April 2019, was performed for Veterans with T2DM and ES‐DFUs following treatment with HDFA. During the study period 29 (n = 29) Veterans with ES‐DFU wounds who received HDFA treatment were identified. Medical record reviews of this retrospective cohort of ES‐DFU Veterans receiving HDFA report 90% (26/29) experiencing complete DFU‐wound closure during the study period. Of the 29 Veterans with ES‐DFUs receiving HDFA, the medical records of nine (30%), with healed wounds, provided documentation suitable for 4 W‐WC, pre‐ and post‐HDFA treatment study comparisons. This study documents significant (P < .05) improvements comparing 4 W‐WC values for standard treatment for Veterans with poorly progressing, worsening or stagnating ES‐DFU‐wounds to those for the same subjects following HDFA treatment. These observations suggest that chronic ES‐DFUs treated with HDFA may experience significantly improved wound closure and complete healing (re‐epithelialization) when compared with standard treatments without HDFA. With validation from RCTs, HDFA may be established as an effective treatment to promote wound healing and closure for nonhealing ES‐DFUs.     

Effect of noncontact normothermic wound therapy on the healing of neuropathic (diabetic) foot ulcers: An interim analysis of 20 patients

This is the interim analysis of a prospective, randomized, controlled study comparing diabetic foot ulcer healing in patients being treated with either noncontact normothermic wound therapy (Warm-UP; Augustine Medical Inc. Eden Prairie, MN) applied for 1 hour 3 times daily until healing or 12 weeks, or standard care (saline-moistened gauze applied once a day). Surgical debridement and adequate foot off-loading was provided to both groups. Evaluations were performed weekly and consisted of acetate tracings, wound assessment, and serial photography. Twenty patients have completed the trial and both treatment groups were distributed evenly (N = 10). Ulcers treated with noncontact normothermic wound therapy had a greater mean percent wound closure than control-treated ulcers at each evaluation point (weeks 1-12). After 12 weeks, 70% of the wounds treated with noncontact normothermic wound therapy were healed compared with 40% for the control group. In this subset of patients there have been no adverse events associated with noncontact normothermic wound therapy.     

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.     

Two-step autologous grafting using HYAFF scaffolds in treating difficult diabetic foot ulcers: results of a multicenter, randomized controlled clinical trial with long-term follow-up

This study evaluated the efficacy and tolerability of an autologous tissue-engineered graft--a 2-step HYAFF autograft--in the treatment of diabetic foot ulcers compared with standard care. In all, 180 patients with dorsal or plantar diabetic foot ulcers (unhealed for ≥1 month) were randomized to receive Hyalograft-3D autograft first and then Laserskin autograft after 2 weeks (n = 90; treatment group) or nonadherent paraffin gauze (n = 90; control group). Efficacy and adverse events were assessed weekly for 12 weeks, at 20 weeks, and at 18 months. The primary efficacy outcome was complete ulcer healing at 12 weeks. Wound debridement, adequate pressure relief, and infection control were provided to both groups. At 12 weeks, complete ulcer healing was similar in both groups (24% of treated vs 21% controls). A 50% reduction in ulcer area was achieved significantly faster in the treatment group (mean 40 vs 50 days; P = .018). Weekly percentage ulcer reduction was consistently higher in the treatment group. At 20 weeks, ulcer healing was achieved in 50% of the treated group as compared with 43% of controls. Dorsal ulcers had a 2.17-fold better chance of wound healing per unit time following autograft treatment (P = .047). In a subgroup with hard-to-heal ulcers, there was a 3.65-fold better chance of wound healing following autograft treatment of dorsal ulcers (P = .035). Adverse events were similar in both groups. The study results demonstrated the potential of this bioengineered substitutes to manage hard-to-heal dorsal foot ulcers.     

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.     

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.     

An aseptically processed,acellular, reticular,allogenic human dermis improves healing in diabetic foot ulcers: A prospective,randomised, controlled,multicentre follow‐up trial

Aseptically processed human reticular acellular dermal matrix (HR‐ADM) has been previously shown to improve wound closure in 40 diabetic patients with non‐healing foot ulcers. The study was extended to 40 additional patients (80 in total) to validate and extend the original findings. The entire cohort of 80 patients underwent appropriate offloading and standard of care (SOC) during a 2‐week screening period and, after meeting eligibility criteria, were randomised to receive weekly applications of HR‐ADM plus SOC or SOC alone for up to 12 weeks. The primary outcome was the proportion of wounds closed at 6 weeks. Sixty‐eight percent (27/40) in the HR‐ADM group were completely healed at 6 weeks compared with 15% (6/40) in the SOC group. The proportions of wounds healed at 12 weeks were 80% (34/40) and 30% (12/40), respectively. The mean time to heal within 12 weeks was 38 days for the HR‐ADM group and 72 days for the SOC group. There was no incidence of increased adverse or serious adverse events between groups or any graft‐related adverse events. The mean and median HR‐ADM product costs at 12 weeks were $1200 and $680, respectively. HR‐ADM is clinically superior to SOC, is cost effective relative to other comparable treatment modalities, and is an efficacious treatment for chronic non‐healing diabetic foot ulcers.     

Failure rates of artificial dermis products in treatment of diabetic foot ulcer: A systematic review and network meta‐analysis

Diabetic foot ulcer (DFU) is a frequent complication in diabetic patients, occurring in up to 25% of those affected. Among the treatments available to clinicians, the use of bioengineered skin substitutes is an attractive alternative. Artificial dermis functions as a matrix, covering the wound and supporting healing and reconstruction of the lost tissue. This study was aimed at reviewing the use of five regeneration matrices (namely, Integra, Nevelia, Matriderm, Pelnac, and Renoskin) as reported by clinical trials. We searched Medline, Embase, ISI Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases for relevant studies. Risk of failure rates was analysed by relative risk ratio method and complete ulcer healing was studied using network meta‐analysis. Thirteen studies (12 randomized clinical trials and one cohort study) were eligible for analysis. The network meta‐analysis based on a single study for Matriderm and 12 studies for other products showed that Matriderm was statistically inferior in achieving complete ulcer healing, as compared to all other products combined. In the second phase analysis, which was limited to three studies using artificial dermis products, there was a 57% reduction in the risk of reepithelialization failure for DFU patients who used Matriderm or Pelnac, compared to those who used Pelnac with basic fibroblast growth factor spray or skin grafting. The data showed an overall low failure rate suggesting that these bioengineered skin products provide a suitable support and microenvironment for healing of DFUs with low ulcer recurrence rates. This systematic review with meta‐analysis highlights the pressing need for more studies investigating the safety, efficacy and failure rates of regeneration matrices in the treatment of 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.