A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial.

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.

Establishing Consensus of Best Practice for CEA Use in Treatment of Severe Burns: A US Burn Provider Delphi Study.

The goal of this study was to inform standards of best practice in the use of cultured epidermal autograft (CEA), manufactured in the United States, for treatment of patients with severe burns. The study was designed using the modified Delphi technique, a method for structuring group communication among experts to promote the development of consensus-based recommendations. Known areas of variability related to the stages of CEA treatment were identified by literature review prior to the study and were confirmed through qualitative interview with the experts. The areas included Preoperative Planning/Surgical Planning, Immediate Post-Operative Care, and Rehabilitation and Long-Term Care. A list of 22 questions was developed based on interviews with the experts, and a 3round Delphi technique was used to establish consensus (≥80% agreement). Following 3 rounds (quantitative, qualitative, and virtual roundtable meeting) of the Delphi study, important guidance for use of CEA treatment in severely burned patients gained consensus. Final key recommendations included minimum burn limit for CEA treatment (30%-50% TBSA), ideal biopsy timing (1-2 days), number of grafts (enough to cover; adjust 72 hours before application), use of dermal substrates (recommended) and wide meshed autograft underlay (recommended), optimal CEA drying time per day (open air >6 hours), slings used if CEA placed on extremities (recommended), dressing changes (performed every day, all at once, with all layers removed down to bridal veil), CEA backing removal (10-14 days post placement), heat lamps (can be used to aid the wound in drying, depending on clinical judgement), initial activity restrictions lifted (beginning 10 days after backing removal), compression garments (introduced at approximately 2 months post CEA surgery), lasers (CO2 laser can be introduced between 3 and 6 months post CEA surgery).

A Prospective Multicenter Study of a Weekly Application Regimen of Viable Human Amnion Membrane Allograft in the Management of Nonhealing Diabetic Foot Ulcers.

Background: Diabetic foot ulcers (DFUs) pose a significant clinical challenge for providers and patients, and often precede devastating complications such as infection, hospitalization, and amputation. Therefore, advanced treatment options are needed to facilitate the healing of chronic DFUs and improve outcomes in this high-risk population. Cryopreserved viable human amnion membrane allograft (vHAMA) has shown great promise in the treatment of recalcitrant DFUs as a supplement to standard of care (SOC). Placental grafts are rich in extracellular matrix proteins, growth factors, and cytokines, which can induce angiogenesis and dermal fibroblast proliferation, resulting in accelerated healing. Methods: In this prospective, multicenter single arm trial, 20 patients with nonhealing DFUs received weekly application of vHAMA, in addition to SOC, for up to 12 weeks. The primary study endpoint was proportion of healed wounds at 12 weeks. Secondary endpoints included proportion of wounds healed at 6 weeks, time to heal, and percentage area wound reduction. Subjects were evaluated for ulcer healing and assessed for adverse events at every treatment visit. Results: At study conclusion, 85% of patients receiving vHAMA healed. Ten wounds healed (50%) by 6 weeks, and 17 wounds (85%) healed by 12 weeks. The mean time to heal was 46.6 days (95% CI: 35.1-58.0), and the average number of vHAMAs used was 5.4 (SD: 3.25). The mean PAR was 86.3% (SD: 40.51). Conclusions: Aseptically processed, cryopreserved vHAMA should be considered as a safe and effective option for DFUs refractory to SOC therapy.

A multicenter, randomized controlled clinical trial evaluating the effects of a novel autologous heterogeneous skin construct in the treatment of Wagner one diabetic foot ulcers: Final analysis.

A novel autologous heterogeneous skin construct (AHSC) was previously shown to be effective versus standard of care (SOC) treatment in facilitating complete wound healing of Wagner 1 diabetic foot ulcers in an interim analysis of 50 patients previously published. We now report the final analysis of 100 patients (50 per group), which further supports the interim analysis findings. Forty-five subjects in the AHSC treatment group received only one application of the autologous heterogeneous skin construct, and five received two applications. For the primary endpoint at 12 weeks, there were significantly more diabetic wounds closed in the AHSC treatment group (35/50, 70%) than in the SOC control group (17/50, 34%) (p = 0.00032). A significant difference in percentage area reduction between groups was also demonstrated over 8 weeks (p = 0.009). Forty-nine subjects experienced 148 adverse events: 66 occurred in 21 subjects (42%) in the AHSC treatment group versus 82 in 28 SOC control group subjects (56.0%). Eight subjects were withdrawn due to serious adverse events. Autologous heterogeneous skin construct was shown to be an effective adjunctive therapy for healing Wagner 1 diabetic foot ulcers.

Surgical Management for Hair Restoration: A Review of Contemporary Techniques.

BACKGROUND: Hair loss can cause psychological distress for patients, regardless of the etiology or extent of the defect. Many conservative and pharmacological approaches are successful in management, but refractory or severe cases often mandate surgical treatment. Surgical techniques have been refined over the course of a century, and we aim to review the most contemporary strategies. METHODS: A review of the literature was performed using the databases PubMed, Web of Science, and Embase, in May 2020. Articles were included if they discussed techniques used within the past 10 years, in search of more contemporary strategies and the most widely used approaches. RESULTS: The use of local flaps, scalp reduction surgery, and hair transplantation techniques are all used for various indications. Modern hair transplantation can be further divided into follicular unit excision and follicular unit transplantation, each with its own advantages. Local flaps are most often used for post-traumatic and reconstructive indication, while hair transplantation can be used for smaller cosmetic lesions or in combination with a variety of other reconstructive techniques. CONCLUSION: Hair loss continues to be a challenging pathology for both patients and physicians, regardless of etiology. When conservative treatment is inadequate, there exist multiple surgical techniques that can feasibly restore hair, though the exact degree of success may vary between patients. The proper technique is dependent upon etiology, patient specific factors, as well as surgeon experience and comfort. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs).

There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

Minimizing bias in a diabetic foot ulcer clinical evaluation: analysis of the HIFLO Trial.

INTRODUCTION: Publications aimed at improving the quality of evidence in wound care clinical research have stressed the importance of minimizing study bias. In particular, lack of a universal definition of healing in wound studies leads to detection bias, resulting in noncomparable healing rates. OBJECTIVE: This report analyzes the steps taken to reduce the main sources of bias in a particular RCT (the HIFLO Trial) that evaluated healing in DFUs using microvascular tissue. MATERIALS AND METHODS: To address "definition of healing"-induced detection bias, 3 blinded adjudicators independently assessed each DFU using a rigorous 4-part definition of healing. Adjudicator responses were analyzed to assess reproducibility. Predefined criteria were also included to avoid bias owing to selection, performance, attrition, and reporting. RESULTS: Rigor and comparability across sites were ensured through investigator training, consistent SOC, data monitoring, and independent statistical and ITT-only analysis. The level of agreement among adjudicators was greater than or equal to 90% for each of the 4-part healing criteria. CONCLUSIONS: High-level agreement by blinded adjudicators confirmed that DFUs in the HIFLO Trial were consistently assessed for healing without bias, validating the most rigorous assessment criteria to date. The findings reported herein may prove beneficial for others seeking to minimize bias in wound studies.

A single arm prospective feasibility study evaluating wound closure with a unique wearable device that provides intermittent plantar compression and offloading in the treatment of non-healing diabetic foot ulcers.

The incidence and economic burden of diabetic foot ulcers continues to rise throughout the world. In this prospective study, a unique device designed to offload the wound, enhance circulation and monitor patient compliance was evaluated for safety and efficacy. The device provides offloading and intermittent plantar compression to improve the pedal flow of oxygenated blood and support wound healing while recording patient use. Ten patients with non-healing diabetic foot ulcers UTgrade 1A/Wagner grade 1 were treated weekly for up to 12 weeks. The primary endpoint was complete wound closure at 12 weeks, and secondary endpoints included healing time, percent area reduction and changes in pain using the visual analogue pain scale. Eight out of ten wounds healed within 12 weeks(80%), and the mean healing time was 41 days(95% CI:24.3-58.3). The percent area reduction was 75(SD:53.9). The baseline visual analogue pain scale was 4.5(2.9) as compared with 3.3(3.4) at end of study. No device-related or serious adverse events were reported. This unique intermediate plantar compression and offloading device may be considered as an alternative for safe and effective for treatment of non-healing diabetic foot ulcers. During treatment, wound healing was significantly accelerated, and pain was improved. Larger randomised controlled trials are underway to validate these early findings.

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers.

BACKGROUND: This randomized controlled trial evaluated the safety and effectiveness of weekly and biweekly applications of dehydrated human amnion and chorion allograft (dHACA) plus standard of care compared to standard of care alone on chronic venous leg ulcers. METHODS: This open-label randomized controlled trial included patients with chronic venous leg ulcers at eight wound care centers across the United States. The primary endpoint was the proportion of healed ulcers at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40 percent closure at 4 weeks and the incidence of adverse events. RESULTS: Among 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more venous leg ulcers healed in the two dHACA-treated groups (75 percent) than in the standard-of-care group (30 percent) ( p = 0.001) even after adjustment for wound area ( p = 0.002), with an odds ratio of 8.7 (95 percent CI, 2.2 to 33.6). There were no significant differences in the proportion of wounds with percentage area reduction greater than or equal to 40 percent at 4 weeks among all groups. The adverse event rate was 63.5 percent. Among the 38 adverse events, none were graft or procedure related, and all were resolved with appropriate treatment. CONCLUSIONS: dHACA and standard of care, either applied weekly or biweekly, significantly healed more venous leg ulcers than standard of care alone, suggesting that the use of aseptically processed dHACA is advantageous and a safe and effective treatment option in the healing of chronic venous leg ulcers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Cost-effectiveness of dehydrated human amnion/chorion membrane allografts in lower extremity diabetic ulcer treatment.

OBJECTIVE: To evaluate the cost-effectiveness and budget impact of using standard care (no advanced treatment, NAT) compared with an advanced treatment (AT), dehydrated human amnion/chorion membrane (DHACM), when following parameters for use (FPFU) in treating lower extremity diabetic ulcers (LEDUs). METHOD: We analysed a retrospective cohort of Medicare patients (2015-2019) to generate four propensity-matched cohorts of LEDU episodes. Outcomes for DHACM and NAT, such as amputations, and healthcare utilisation were tracked from claims codes, analysed and used to build a hybrid economic model, combining a one-year decision tree and a four-year Markov model. The budget impact was evaluated in the difference in per member per month spending following completion of the decision tree. Likewise, the cost-effectiveness was analysed before and after the Markov model at a willingness to pay (WTP) threshold of $100,000 per quality adjusted life year (QALY). The analysis was conducted from the healthcare sector perspective. RESULTS: There were 10,900,127 patients with a diagnosis of diabetes, of whom 1,213,614 had an LEDU. Propensity-matched Group 1 was generated from the 19,910 episodes that received AT. Only 9.2% of episodes were FPFU and DHACM was identified as the most widely used AT product among Medicare episodes. Propensity-matched Group 4 was limited by the 590 episodes that used DHACM FPFU. Episodes treated with DHACM FPFU had statistically fewer amputations and healthcare utilisation. In year one, DHACM FPFU provided an additional 0.013 QALYs, while saving $3,670 per patient. At a WTP of $100,000 per QALY, the five-year net monetary benefit was $5003. CONCLUSION: The findings of this study showed that DHACM FPFU reduced costs and improved clinical benefits compared with NAT for LEDU Medicare patients. DHACM FPFU provided better clinical outcomes than NAT by reducing major amputations, ED visits, inpatient admissions and readmissions. These clinical gains were achieved at a lower cost, in years 1-5, and were likely to be cost-effective at any WTP threshold. Adoption of best practices identified in this retrospective analysis is expected to generate clinically significant decreases in amputations and hospital utilisation while saving money.

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.

Multi-centre prospective randomised controlled clinical trial to evaluate a bioactive split thickness skin allograft vs standard of care in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) pose a significant risk for infection and limb loss. Advanced wound therapies including human skin allografts have shown promise in resolving these challenging wounds. The primary objective of this randomised, prospective study was to compare the response of 100 subjects with non-healing DFUs of which 50 were treated with a cryopreserved bioactive split thickness skin allograft (BSA) (TheraSkin; Misonix,Inc., Farmingdale, NY) compared with 50 subjects treated with standard of care (SOC, collagen alginate dressing) at 12 weeks. Both groups received standardised care that included glucose monitoring, weekly debridement's as appropriate, and an offloading device. The primary endpoint was proportion of full-thickness wounds healed at 12 weeks, with secondary endpoints including differences in percent area reduction (PAR) at 12 weeks, changes in Semmes-Weinstein monofilament score, VAS pain, and w-QoL. The result illustrated in the intent-to-treat analysis at 12 weeks showed that 76% (38/50) of the BSA-treated DFUs healed compared with 36% (18/50) treated with SOC alone (adjusted P = .00056). Mean PAR at 12 weeks was 77.8% in the BSA group compared with 49.6% in the SOC group (adjusted P = .0019). In conclusion, adding BSA to SOC appeared to significantly improve wound healing with a lower incidence of adverse events related to treatment compared with SOC alone.

Improved healing of chronic diabetic foot wounds in a prospective randomised controlled multi-centre clinical trial with a microvascular tissue allograft.

This study assesses the impact of a processed microvascular tissue (PMVT) allograft on wound closure and healing in a prospective, single-blinded, multi-centre, randomised controlled clinical trial of 100 subjects with Wagner Grade 1 and 2 chronic neuropathic diabetic foot ulcerations. In addition to standard wound care, including standardised offloading, the treatment arm received PMVT while the control arm received a collagen alginate dressing. The primary endpoint was complete wound closure at 12 weeks. Secondary endpoints assessed on all subjects were percent wound area reduction, time to healing, and local neuropathy. Novel exploratory sub-studies were conducted for wound area perfusion and changes in regional neuropathy. Weekly application of PMVT resulted in increased complete wound closure at 12 weeks (74% vs 38%; P = .0003), greater percent wound area reduction from weeks four through 12 (76% vs 24%; P = .009), decreased time to healing (54 days vs 64 days; P = .009), and improved local neuropathy (118% vs 11%; P = .028) compared with the control arm. Enhanced perfusion and improved regional neuropathy were demonstrated in the sub-studies. In conclusion, this study demonstrated increased complete healing with PMVT and supports its use in treating non-healing DFUs. The observed benefit of PMVT on the exploratory regional neuropathy and perfusion endpoints warrants further study.

A multicentre, randomised controlled clinical trial evaluating the effects of a novel autologous, heterogeneous skin construct in the treatment of Wagner one diabetic foot ulcers: Interim analysis.

We desired to carefully evaluate a novel autologous heterogeneous skin construct in a prospective randomised clinical trial comparing this to a standard-of-care treatment in diabetic foot ulcers (DFUs). This study reports the interim analysis after the first half of the subjects have been analysed. Fifty patients (25 per group) with Wagner 1 ulcers were enrolled at 13 wound centres in the United States. Twenty-three subjects underwent the autologous heterogeneous skin construct harvest and application procedure once; two subjects required two applications due to loss of the first application. The primary endpoint was the proportion of wounds closed at 12 weeks. There were significantly more wounds closed in the treatment group (18/25; 72%) vs controls (8/25; 32%) at 12 weeks. The treatment group achieved significantly greater percent area reduction compared to the control group at every prespecified timepoint of 4, 6, 8, and 12 weeks. Thirty-eight adverse events occurred in 11 subjects (44%) in the treatment group vs 48 in 14 controls (56%), 6 of which required study removal. In the treatment group, there were no serious adverse events related to the index ulcer. Two adverse events (index ulcer cellulitis and bleeding) were possibly related to the autologous heterogeneous skin construct. Data from this planned interim analysis support that application of autologous heterogeneous skin construct may be potentially effective therapy for DFUs and provide supportive data to complete the planned study.

A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are at risk for detrimental complications even with current, standard of care (SOC) treatments. The primary objective of this randomised controlled trial was to compare a unique resorbable glass microfiber matrix (Mirragen; Advanced Wound Matrix [BBGFM]; ETS Wound Care, Rolla, Missouri) compared with a standard of care group (SOC, collagen alginate dressing) at 12 weeks. Both groups received standard diabetic foot care including glucose monitoring, weekly debridements when needed and an offloading device. The primary endpoint was proportion of full-thickness, non-infected, non-ischaemic wounds healed at 12 weeks, with secondary endpoints including percent area reduction (PAR) and changes in Semmes-Weinstein monofilament testing. The result illustrated in the intent-to-treat analysis at 12 weeks showed that 70% (14/20) of the BBGFM-treated DFUs healed compared with 25% (5/20) treated with SOC alone (adjusted P = .006). Mean PAR at 12 weeks was 79% in the BBGFM group compared with 37% in the SOC group (adjusted P = .027). Mean change in neuropathic score between baseline and up to 12 weeks of treatment was 2.0 in the BBGFM group compared with -0.6 in the SOC group where positive improvement in scores are better (adjusted P = .008). The mean number of BBGFM applications was 6.0. In conclusion, adding BBGFM to SOC significantly improved wound healing with no adverse events related to treatment compared with SOC alone.

Evaluating an urban pediatric hospital's scald burn prevention program.

BACKGROUND: Over 450,000 individuals are hospitalized with burns annually and roughly 35% are scald burns. Children younger than 5 years of age are at the greatest risk of scald burn injury. Caregiver burn prevention programs have been found to reduce the prevalence of injuries in young children; however, low-income and underserved populations seldomly have access to these programs. The impact of scald burn prevention programs in underserved populations remains unexplored. The objective of the current study was to evaluate the efficacy of a scald burn prevention program at a Level One Pediatric Trauma Center in a low-income, underserved community. METHODS: Our hospital developed a one-hour scald burn prevention program for caregivers with children 5 years of age or younger. The program educated caregivers on ways to prevent scald burns and create safeguards in their home. Caregivers completed a pre-post survey to measure their ability to identify hot or cold objects, as well as respond to items about their perceptions of the program's utility, their willingness to share it with others, and the likelihood that they would use the information in the future. Data was analyzed using a paired t-test. RESULTS: Two-hundred and sixty-nine (N = 269) caregivers participated in the program. Before the program, caregivers could identify potentially hot objects 83.17% of the time, and after the program, they were able to identify these items 92.31% of the time: t (268) = 12.46, p < .001, d = 1.07. Additionally, 95% of caregivers indicated that the program was helpful, 99% stated that they were likely to share this information with others, and 100% indicated that they would use the information from the program. CONCLUSIONS: Education is a critical component to prevent scald burns. Results indicate that a hospital-led scald burn prevention program can positively impact a caregiver's ability to identify possible scald-burn risks. Providing education to caregivers who typically do not receive this information could lower the prevalence of scald burns not only institutionally, but in communities that are disproportionately impacted by this mechanism of injury.

Observed impact of skin substitutes in lower extremity diabetic ulcers: lessons from the Medicare Database (2015-2018).

OBJECTIVE: To evaluate large propensity-matched cohorts to assess outcomes in patients receiving advanced treatment (AT) with skin substitutes for lower extremity diabetic ulcers (LEDUs) versus no AT (NAT) for the management of LEDUs. METHOD: The Medicare Limited Dataset (1 October 2015 through 2 October 2018) were used to retrospectively analyse people receiving care for a LEDU treated with AT or NAT (propensity-matched Group 1). Analysis included major and minor amputations, emergency department (ED) visits and hospital readmissions. In addition, AT following parameters for use (FPFU) was compared with AT not FPFU (propensity-matched Group 2). A paired t-test was used for comparisons of the two groups. For comparisons of three groups, the Kruskal-Wallis test was used. A Bonferroni correction was performed when multiple comparisons were calculated. RESULTS: There were 9,738,760 patients with a diagnosis of diabetes, of whom 909,813 had a LEDU. In propensity-matched Group 1 (12,676 episodes per cohort), AT patients had statistically fewer minor amputations (p=0.0367), major amputations (p<0.0001), ED visits (p<0.0001), and readmissions (p<0.0001) compared with NAT patients. In propensity-matched Group 2 (1131 episodes per cohort), AT FPFU patients had fewer minor amputations (p=0.002) than those in the AT not FPFU group. CONCLUSION: AT for the management of LEDUs was associated with significant reductions in major and minor amputation, ED use, and hospital readmission compared with LEDUs managed with NAT. Clinics should implement AT in accordance with the highlighted parameters for use to improve outcomes and reduce costs.

Functional Properties of a Purified Reconstituted Bilayer Matrix Design Support Natural Wound Healing Activities.

Biomaterial engineering has produced numerous matrices for use in tissue repair, utilizing various materials and processing methods, which can impact the ability of the products to encourage wound healing. Recently, we observed favorable clinical outcomes, using a novel purified reconstituted bilayer matrix (PRBM; Geistlich Derma-Gide) to treat chronic diabetic foot ulcers. METHODS: Evaluations of the structural and functional characteristics of PRBM in vitro were performed to assess how this biomaterial may affect the favorable clinical results observed by influencing the wound environment and key physiologic mechanisms necessary for the healing process. Investigations included scanning electron microscopy, cell culture analyses, gene expression assays, matrix metalloproteinase activity assessment, and pH measurement. RESULTS: Cross-sectional scanning electron microscopy demonstrated a distinct bilayer structure with porous and compact layers. The PRBM structure allowed cell types involved in wound healing to bind and proliferate. Expression analysis of growth factor-responsive genes demonstrated binding and preservation of bioactive growth factors TGF-ß1, bFGF, and VEGF by PRBM. Boyden chamber migration assays revealed increased cellular migration compared with controls. In the presence of PRBM, the activity of MMP-1, MMP-2, and MMP-9 was significantly lower compared with control samples. pH of the PRBM in solution was slightly acidic. CONCLUSIONS: Based on in vitro evaluations, it appears that the PRBM processing without deleterious chemical crosslinking results in a suitable ECM possessing characteristics to aid natural wound healing, including cell attachment, migration, proliferation, differentiation, and angiogenesis. These in vitro data support the promising healing rate observed clinically when chronic DFUs are treated with PRBM.

Open-label Venous Leg Ulcer Pilot Study Using a Novel Autolologous Homologous Skin Construct.

Venous leg ulcers (VLUs) are often refractory to compression therapy, and their prevalence is increasing. An autologous homologous skin construct (AHSC) that uses the endogenous regenerative capacity of healthy skin has been developed to treat cutaneous defects, with a single application. The ability of AHSC to close VLUs with a single treatment was evaluated in an open-label, single-arm feasibility study to test the hypothesis that AHSC treatment will result in wound closure by providing healthy autologous tissue to the wound bed. METHODS: Ten VLUs were treated with a single application of AHSC. A 1.5 cm2 full-thickness skin harvest from the proximal calf was collected and sent to a Food and Drug Administration-registered facility, where it was processed into AHSC and returned to the provider within 48 hours. AHSC was spread evenly across the wound and dressed with silicone. The primary endpoint was wound closure rate at 12 weeks. Wound closure was followed with 3-dimensional planimetry, and closure was confirmed by a panel of plastic surgeons. Additional endpoints followed for 12 weeks included graft take, harvest site closure, adverse event rate, complications, and patient-reported pain. RESULTS: All 10 VLUs demonstrated successful graft take as evidenced by graft persisting in wound and harvest site closure. Eight VLUs exhibited complete closure within 12 weeks. One VLU that failed to heal with a prior split thickness skin graft closed within 13.5 weeks with AHSC. The mean time of closure was 34 days (95% confidence interval, 14-53). Pain improved by closure confirmation visit. There was 1 serious adverse event unrelated to the product or procedure. CONCLUSION: This pilot study demonstrated that AHSC may be a viable single-application topical intervention for VLUs and warrants further investigation in larger, controlled studies.