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In contrast to tangential excision, enzymatic debridement with NexoBrid® selectively removes non-viable tissue, allowing some deep dermal burn woundsto still heal conservatively. In thisretrospective study, we investigated the reduction in surgery and associated scarring following enzymatic debridement in definitely deep burns as proven by laser Doppler imaging. One hundred two exclusively laser Dopplerimaging-blue regions of interest where there was no doubt at all about the surgical indication, were selected for analysis in 32 patients treated with NexoBrid®. The total surface area of the 102 exclusively blue regions of interest was 5,086.4cm². NexoBrid® resulted in a substantial reduction in the need for autografts as 1,986.9cm² (39%) healed with conservative treatment. This corresponded with a significant reduction in patients(56.3%) requiring surgery. Exclusively laser Doppler imaging-blue regions of interest treated surgically with split thickness skin grafts required significantly more time to heal compared to conservative treatment (37.8±17.5 vs. 27.0±10.5 days). Avery limited rate of hypertrophic scarring (16.7%) was observed. Thisisthe first paper demonstrating a proven and significant reduction in the extent of autografting as well asin the number of surgical procedures afterselective enzymatic debridement in objectively laser Doppler imaging-defined and therefore proven deep burns. Even after extended conservative treatment with prolonged healing timesfollowing NexoBrid®, hypertrophic scar formation waslimited (5/54 regions of interest, 9.3%). Also in operated patients, the incidence of hypertrophic scarring following a strict regimen of aftercare was low (12/48 regions of interest, 25%). [ABSTRACT FROM AUTHOR]

Introduction: Advancements in resuscitative care and burn surgery have improved survival rates after extensive burn injuries, shifting focus to enhancing the quality of survival. Conventional treatment with split-thickness skin grafts (STSG) presents limitations such as donor-site morbidity, limited availability in extensive burn injuries, and hypertrophic scarring. Tissue engineering aims to address these drawbacks by developing optimal skin substitutes. This systematic review aims to provide an overview of the current applications of cultured cells in burn surgery, encompassing diverse approaches and addressing existing challenges to enhance burn wound management and improve patient outcomes., Methods: Following PRISMA guidelines, a comprehensive search was performed across three databases (PubMed, Embase, Cochrane Library) for articles on cultured cell use in burn treatment. Only clinical studies were included. Articles were screened by two independent reviewers. Quality assessment was performed., Results: The search yielded 167 articles, of which 14 met the eligibility criteria. The selection included 8 randomized controlled trials, 5 prospective cohort trials, and 1 retrospective cohort study. Various tissue-engineered skin substitutes, from cultured epidermal autografts to dermal regeneration templates seeded with cultured cells, showed promising outcomes. Several substitutes exhibited take rates comparable to STSG with improved scar quality., Conclusion: Results are promising, though standardization of cultured skin substitutes and robust clinical trials with larger populations and appropriate comparators are still lacking., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly( ε -caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization ( 1 H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

Objective: Burn injuries pose a heightened risk of infection, which is primarily responsible for increased morbidity and mortality. Factors such as extensive skin damage and compromised immunity exacerbate this vulnerability. Pseudomonas aeruginosa and Staphylococcus aureus are frequently identified in burns, with Gram-negative Pseudomonas aeruginosa often resistant to antibacterial agents. While Flaminal, an alginate-based wound dressing (Flen Health, Belgium), aids wound healing, its antibacterial effects are limited compared with 1% silver sulfadiazine (1% SSD). In contrast, Prontosan Wound Gel X, a betaine and polyhexanide-based hydrogel (B. Braun Medical AG, Switzerland), has been shown to effectively combat various microbes and promotes wound healing., Method: In this study, two research cohorts were retrospectively established (control group: patients receiving standard of care with the alginate-based wound dressing; intervention group: patients receiving the polyhexanide hydrogel wound dressing), comprising patients admitted to a burn centre between 2019 and 2022. Patients were eligible when continuous wound treatment with either of the two wound dressings was performed. Laser Doppler imaging (LDI) scans were conducted. Regions of interest (ROIs) were selected based on LDI scans and divided into healing time categories. Wound swabs were collected and the presence of Pseudomonas aeruginosa and Staphylococcus aureus was documented. Bacterial load was evaluated using a semiquantitative scale. Wound healing was recorded., Results: The control group consisted of 31 patients with 93 ROIs, while the intervention group had 67 ROIs involving 29 patients. Both groups exhibited similar proportions of healing time categories (p>0.05). The polyhexanide hydrogel dressing outperformed the alginate-based dressing in antiseptic efficacy by significantly reducing the incidence of Pseudomonas aeruginosa - and Staphylococcus aureus -positive cultures in patients' wounds. Wound healing time for conservative treatment was comparable between groups., Conclusion: In this study, the polyhexanide hydrogel dressing minimised Pseudomonas aeruginosa and Staphylococcus aureus colonisation in burn wounds, demonstrating strong antibacterial properties, emphasising its potential to minimise infections in burn injuries.

In contrast to tangential excision, enzymatic debridement with NexoBrid ® selectively removes non-viable tissue, allowing some deep dermal burn wounds to still heal conservatively. In this retrospective study, we investigated the reduction in surgery and associated scarring following enzymatic debridement in definitely deep burns as proven by laser Doppler imaging. One hundred two exclusively laser Doppler imaging-blue regions of interest where there was no doubt at all about the surgical indication, were selected for analysis in 32 patients treated with NexoBrid ® . The total surface area of the 102 exclusively blue regions of interest was 5,086.4cm 2 . NexoBrid ® resulted in a substantial reduction in the need for autografts as 1,986.9cm 2 (39%) healed with conservative treatment. This corresponded with a significant reduction in patients (56.3%) requiring surgery. Exclusively laser Doppler imaging-blue regions of interest treated surgically with split thickness skin grafts required significantly more time to heal compared to conservative treatment (37.8±17.5 vs. 27.0±10.5 days). A very limited rate of hypertrophic scarring (16.7%) was observed. This is the first paper demonstrating a proven and significant reduction in the extent of autografting as well as in the number of surgical procedures after selective enzymatic debridement in objectively laser Doppler imaging-defined and therefore proven deep burns. Even after extended conservative treatment with prolonged healing times following NexoBrid ® , hypertrophic scar formation was limited (5/54 regions of interest, 9.3%). Also in operated patients, the incidence of hypertrophic scarring following a strict regimen of aftercare was low (12/48 regions of interest, 25%)., (© 2023 Euro-Mediterranean Council for Burns and Fire Disasters.)

Non-invasive scar management typically involves pressure therapy, hydration with silicones or moisturizers, and UV protection. Moisture loss from scars can lead to hypertrophic scar formation. Pressure therapy reduces blood flow, fibroblast activity, and transforming growth factor beta 1 (TGF-β1) release. This study examined various moisturizers and liquid silicone gel's impact on microcirculation. 40 volunteers participated in a study where superficial abrasions were created to induce trans epidermal water loss (TEWL). Five moisturizers (TEDRA ® , TEDRA ® NT1, TEDRA ® NT3, Alhydran ® , Lipikar ® ) and BAP Scar Care ® silicone gel were tested. TEWL, hydration, and blood flow were measured up to 4 h post-application. Results showed that silicone had the least impact on occlusion and hydration. Alhydran ® reduced blood flow the most, while Lipikar ® increased it the most. TEDRA ® NT1 had reduced flow compared to TEDRA ® and TEDRA ® NT3. All TEDRA ® products exhibited high hydration, and all but silicone showed good occlusion. Moisturizers influenced skin microcirculation, with some causing decrease, while others increased flow. However, the clinical impact on scarring remains unclear compared to the evident effects of hydration and occlusion. More research is necessary to study moisturizers alone and with pressure therapy on scars, along with potential adverse effects of increased microcirculation on scars.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Burn eschar removal by enzymatic debridement with NexoBrid ® (EDNX) results in a maximum preservation of all viable tissue, which is the main advantage over traditional tangential excision. The authors participated in a marketing authorization holder process to obtain reimbursement from the national health authorities in Belgium., Material and Methods: The reimbursement process consisted of three phases, as specified by the reimbursement regulations required by the Belgian National Institute for Health and Disability Insurance (NIHDI)., Results: Forty-one patients with clinically deep 2nd and 3rd degree burns, treated with EDNX in two Belgian burn centers, were included in the registry for the first phase of the reimbursement process. The total success rate of the EDNX treatment was 95.1% (39/41). Over half of the burn wounds treated with NexoBrid ® (55.2%) did not require any additional surgical debridement or skin grafting. To obtain definitive reimbursement, an extra 16 patients were included. In this population, 51.4% did not require any surgical intervention. The total success rate of the EDNX debridement in this group was 100%. Based on an estimated market share of 12% and around 75 patients in the third year after final reimbursement, a market access consultant calculated that NexoBrid ® will realize yearly savings for the Belgian Healthcare budget of at least €30.000., Conclusion: Based on the results of this Belgian registry study in combination with the yearly healthcare budget savings, the NIHDI granted a final reimbursement for EDNX treatment in adults, endorsed by the Minister of Health on November 5 th , 2019.

Background: Hypertrophic scarring is a deviate occurrence after wound closure and is a common burn sequela. The mainstay of scar treatment consists of a trifold approach: hydration, UV-protection and the use of pressure garments with or without extra paddings or inlays to provide additional pressure. Pressure therapy has been reported to induce a state of hypoxia and to reduce the expression pattern of transforming growth factor-β1 (TGF-β1), therefore limiting the activity of fibroblasts. However, pressure therapy is said to be largely based on empirical evidence and a lot of controversy concerning the effectiveness still prevails. Many variables influencing its effectivity, such as adherence to treatment, wear time, wash frequency, number of available pressure garment sets and amount of pressure remain only partially understood. This systematic review aims to give a complete and comprehensive overview of the currently available clinical evidence of pressure therapy., Methods: A systematic search for articles concerning the use of pressure therapy in the treatment and prevention of scars was performed in 3 different databases (Pubmed, Embase, and Cochrane library) according to the PRISMA statement. Only case series, case-control studies, cohort studies, and RCTs were included. The qualitative assessment was done by 2 separate reviewers with the appropriate quality assessment tools., Results: The search yielded 1458 articles. After deduplication and removal of ineligible records, 1280 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 17 articles were included. Comparisons between pressure or no pressure, low vs high pressure, short vs long duration and early vs late start of treatment were investigated., Conclusion: There is sufficient evidence that indicates the value of prophylactic and curative use of pressure therapy for scar management. The evidence suggests that pressure therapy is capable of improving scar color, thickness, pain, and scar quality in general. Evidence also recommends commencing pressure therapy prior to 2 months after injury, and using a minimal pressure of 20-25 mmHg. To be effective, treatment duration should be at least 12 months and even preferably up to 18-24 months. These findings were in line with the best evidence statement by Sharp et al. (2016)., Competing Interests: Declarations of interest None, there are no conflicts of interest for the authors., (Copyright © 2023 Elsevier Ltd and ISBI. All rights reserved.)

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment.

Background: Absence of almost the entire reticular dermal layer is inherent to the use of autologous split-thickness skin grafting (STSG) to close full-thickness wounds, often resulting in hypertrophic scars and contractures. Many dermal substitutes have been developed, but unfortunately most have varying results in terms of cosmetic and/or functional improvement as well as patient satisfaction, in addition to high costs. Bilayered skin reconstruction using the human-derived glycerolized acellular dermis (Glyaderm®) has been reported to result in significantly improved scar quality using a two-step procedure. Unlike the necessary two-step procedure for most commercially available dermal substitutes, in this study we aimed to investigate the use of Glyaderm® in a more cost-effective single-stage engrafting. This is a method which, if autografts are available, is preferred by the majority of surgeons given the reduction in costs, hospitalization time and infection rate., Methods: A prospective, randomized, controlled, intra-individual, single-blinded study was performed, investigating the simultaneous application of Glyaderm® and STSG vs. STSG alone in full-thickness burns or comparable deep skin defects. During the acute phase, bacterial load, graft take and time to wound closure were assessed and were the primary outcomes. Aesthetic and functional results (secondary outcomes) were evaluated at 3, 6, 9 and 12 months follow-up using subjective and objective scar measurement tools. Biopsies for histological analysis were taken at 3 and 12 months., Results: A total of 66 patients representing 82 wound comparisons were included. Graft take (>95%), pain management and healing time were comparable in both groups. At 1 year follow-up, the overall Patient and Observer Scar Assessment Scale assessed by the patient was significantly in favour of sites where Glyaderm® was used. Not infrequently, patients attributed this difference to improved skin sensation. Histological analysis showed the presence of a well-formed neodermis, with donor elastin present for up to 12 months., Conclusions: A single-stage bilayered reconstruction with Glyaderm® and STSG results in optimal graft take without loss of Glyaderm® nor the overlaying autografts due to infection. The presence of elastin in the neodermis was demonstrated during long-term follow-up in all but one patient, which is a crucial factor contributing to the significantly improved overall scar quality as evaluated by the blinded patients., Trial Registration: The trial was registered on clinicaltrials.gov and received the following registration code: NCT01033604., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer-based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non- to minimally-invasive alternative to percutaneous injection., (© 2023 Japanese Dermatological Association.)

Background: The mainstay of non-invasive scar management, consists of pressure therapy with customized pressure garments often combined with inlays, hydration by means of silicones and/or moisturizers as well as UV protection. It is generally accepted that scar dehydration resulting from impaired barrier function of the stratum corneum and expressed by raised trans epidermal water loss (TEWL) values, can lead to increased fibroblast activity and thereby hypertrophic scar formation. However, we have reached no consensus on exactly what optimal scar hydration is nor on barrier function repair: by means of silicone sheets, liquid silicone gels or moisturizers. Occlusive silicone sheets almost completely prevent TEWL and have been shown to be effective. Nevertheless, many important disadvantages due to excessive occlusion such as difficulties in applying the sheets exceeding 10-12 h, pruritus, irritation, and maceration of the skin are limiting factors for its use. To avoid these complications and to facilitate the application, liquid silicone gels were developed. Despite a reduced occlusion, various studies have shown that the effects are comparable to these of the silicone sheets. However, major limiting factors for general use are the long drying time, the shiny aspect after application, and the high cost especially when used for larger scars. Based on excellent clinical results after using three specific moisturizers for scar treatment in our patients, we wanted to investigate whether these moisturizers induce comparable occlusion and hydration compared to both each other and the widely recognized liquid silicone gels. We wanted to provide a more scientific basis for the kind of moisturizers that can be used as a full-fledged and cost-effective alternative to silicone gel., Methods: A total of 36 healthy volunteers participated in this study. Increased TEWL was created by inducing superficial abrasions by rigorous (20x) skin stripping with Corneofix® adhesive tape in squares of 4 cm². Three moisturizers and a fluid silicone gel were tested: DermaCress, Alhydran, Lipikar and BAP Scar Care silicone gel respectively. TEWL reducing capacities and both absolute (AAH) and cumulative (CAAH) absolute added hydration were assessed using a Tewameter® TM300 and a Corneometer® CM825 at different time points for up to 4 h after application., Results: We found an immediate TEWL increase in all the zones that underwent superficial abrasions by stripping. Controls remained stable over time, relative to the ambient condition. The mean percentage reduction (MPR) in TEWL kept increasing over time with Alhydran and DermaCress, reaching a maximum effect 4 h after application. Silicone gel reached maximal MPR almost immediately after application and only declined thereafter. The silicone gel never reached the minimal MPR of Alhydran or DermaCress. Hydration capacity assessed through CAAH as measured by the Corneometer was significantly less with silicone gel compared to the moisturizers. Compared to silicone gel Lipikar provided similar occlusion and the improvement in hydration was highly significant 4 h after application., Conclusion: Based on the results of both our previous research and this study it is clearly demonstrated that the occlusive and hydrative effect of fluid silicone gel is inferior to the moisturizers used in our center. Lipikar hydrates well but is less suitable for scar treatment due to the lack of occlusion. A well-balanced occlusion and hydration, in this study only provided by Alhydran and DermaCress, suggests that moisturizers can be used as a scar hydration therapy that replaces silicone products, is more cost-effective and has a more patient-friendly application., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: Autologous split thickness skin grafting is the standard-of-care for most deep dermal and full thickness skin defects. Historically, mesh grafting is used to expand skin grafts for smaller defects and other techniques such as Meek micrografting is used to enable expansion for larger skin defects. Yet, Meek micrografting is increasingly used for smaller skin defects as well. Both techniques are frequently used, especially in burn centers, but evidence on which one is preferable for relative smaller skin defects is lacking. Therefore, an intra-patient randomized controlled trial was designed to adequately compare multiple outcomes of the Meek micrografting and mesh grafting techniques., Materials and Methods: A multicenter intra-patient controlled randomized trial is being performed in two burn centers (the Netherlands and Belgium) to compare multiple outcomes of Meek micrografting and mesh grafting burns or skin defects. Study registration number (NL74274.029.20). Adult patients with a (burn) wound and an indication for surgical excision and skin grafting were screened for inclusion. In total 70 patients will be included and the primary outcome is scar quality twelve months post-surgery assessed by the Patient and Observer Scar Assessment Scale. Moreover, graft take, re-epithelialization, infection rate, donor site size and patients' preference are also measured within hospital admission, on 3 months and 12 months post-surgery., Discussion: This is the first randomized trial that is intra-patient controlled, which enables a proper comparison between both skin expansion techniques. The results of this study will contribute to the clarification of the indications of both techniques and ample attention is paid for the patients' opinion on the surgical treatment options., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rijpma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In recent years, it has become clear that the burn eschar in deep burns can be selectively removed using the enzymatically debriding agent NexoBrid® (EDNX). In deep partial-thickness burns, such selective debridement preserves all non-injured dermis, which is sometimes sufficient for spontaneous re-epithelization. Nevertheless, it can be extremely challenging to determine exactly what and when to operate after an EDNX procedure. In this manuscript, we sought to investigate the clinical aspect of the enzymatically debrided wound bed of laser Doppler imaging (LDI)-confirmed deep dermal and full-thickness burns after NexoBrid® application. This to evaluate the residual wound healing capacity and implement specific indications for surgical therapy after enzymatic debridement., Material and Methods: Mainly LDI-blue areas, determined between 48 h and 5d after burn and afterwards treated with EDNX were selected. Six practical and three expert EDNX users evaluated the high-quality digital images of the wound beds immediately post NexoBrid® removal and after a 2 h wet-to-dry (WTD) dressing period., Results: One hundred and two mainly LDI-blue areas in 32 patients were analyzed. Regarding the early decision-making, there were no significant differences in the wound bed evaluations, wound healing assessment and treatment decision of all 9 EDNX users post EDNX removal versus post WTD. Moreover, there was a good to excellent consensus between the practical and expert EDNX users in the individual wound bed evaluations. Even in the evaluation of a newly developed wound bed color code, with 7 different colors/patterns to choose from, the consensus was 80%. There was also an 84% consensus on the decision whether or not to operate. All mainly LDI-blue areas with incomplete enzymatic debridement, determined during clinical investigation by expert EDNX users, required surgery. Additionally, the expert investigators demonstrated that the following wound bed characteristics were independent predictors of the need for surgical treatment: visible fat lobules (p = 0.028), translucent fat lobules (p < 0.001), dermal step-off in the wound bed (p < 0.001), visible blood vessels (p < 0.001) and coagulated blood vessels (p = 0.023). Also, higher color code ranges on our own developed wound bed classification were significantly related to a surgical intervention (p = 0.006). When including the LDI flux values, the perfusion units were significantly different (p < 0.001) between the exclusively LDI-blue areas treated conservatively (mean 145.7) and the areas ultimately treated with autografts (mean 119.5)., Conclusion: To the best of our knowledge, this study is the first to address the clinical wound bed evaluation of LDI-confirmed deep burns after NexoBrid® application. Based on our results, it is recommended to evaluate the wound bed twice: immediately after removing NexoBrid® to assess the viability of the wound bed and after the WTD period to reach a more complete decision. During these evaluations, wound bed characteristics such as incomplete debridement, visible and/or translucent fat lobules, visible and/or coagulated blood vessels and a dermal step-off in the wound bed combined with a higher range (4-5) in the newly developed wound bed color code should lead to an early and reliable decision for skin grafting. For burn centers using LDI, mean flux values below 119.5PU - in addition to the above-mentioned wound bed evaluation - are a clear indicator for surgical therapy., Competing Interests: Declaration of interest Dr. Yaron Shoham is a freelance consultant for MediWound Ltd. There are no conflicts of interest for the other authors., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Hypertrophic scarring (HTS) is frequently observed after deep dermal and full-thickness skin defects. Local drug delivery in HTS has been shown more effective compared to other (minimally) invasive treatments. Disadvantages being operator-dependency and non-uniform drug distribution. Moreover, injections are painful and difficult when confronted with extensive scars or HTS in children. Corticoid-embedded dissolving microneedles (CEDMN) were developed that provide painless skin penetration and direct dermal drug delivery. Hyaluronic acid-based DMN and CEDMN patches were utilized. Structural analysis was performed via nuclear magnetic resonance (NMR) spectroscopy while gel permeation chromatography (GPC) was applied to determine chain length (molar mass) and dispersity of hyaluronic acid. Mechanical properties were evaluated by compression testing. Five burn victims with HTS were included. For each individual, three comparable scars were chosen. One control scar was left untreated. Two scars were treated with either 600 or 800 µm CEDMN patches. Patients were treated monthly for 4 months. Treatment with 800 µm CEDMN was initiated after 8 weeks. Assessor-blinded POSAS was registered. Hydration, evaporation, color and elasticity were recorded. The physico-chemical characterization suggests that the mechanical properties enable skin penetration and adequate drug delivery. Patients experienced the therapy as painless. According to the POSAS, all scars improved over time. However, the scars that were treated with CEDMN patches improved faster and with increased increment. The 800 µm CEDMN ensured the fastest POSAS-decrease. Hyaluronic acid-based CEDMN patches are valuable alternatives to intracicatrical injections, as they offer a painless and effective method for administering corticosteroids in HTS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The closure of extensive burn wounds with widely expanded autologous split-thickness skin grafts (STSG) is associated with undesirable scar formation and contraction, due to the lack of dermis. Various materials for dermal replacement have been developed, either of xenogeneic, allogeneic or synthetic origin and are placed in the wound underneath a thin STSG in order to improve scar quality. In this study, a porcine wound model was used to compare several commercially available acellular dermal substitutes with an acellular dermal substitute prepared from glycerol preserved human skin: Glyaderm Ⓡ ., Methods: Antigenic components of the allografts were removed by incubation in the 0.06 M NaOH solution. In the first experiments, the dermal substitutes were applied to full thickness wounds and covered simultaneously with STSG. Controls were covered with STSG only. The wound healing response was analyzed for 8 weeks, both macroscopically and histologically. The Mann-Whitney U test was used for statistical analysis. In the second series of experiments, Glyaderm Ⓡ was applied in a two-stage procedure in comparison to Integra. The STSG was placed on the dermal substitutes one week later., Results: In the first series, the inflammatory response and myofibroblast influx in Glyaderm Ⓡ were limited, indicating possible beneficial outcomes on final wound healing results. The survival of the STSG on the acellular dermis was lower compared to the control wounds. Second series: the take of the STSG was the same as in the controls, but additionally wound contraction was reduced. The application of Glyaderm Ⓡ was non-inferior to Integra., Conclusion: Glyaderm Ⓡ can be successfully used for the reduction of wound contraction when applied in a two-stage procedure., (© 2022 The Author(s).)

Introduction: Autologous split thickness skin grafting is the standard-of-care for the majority of deep dermal and full thickness burns: Meshed grafting is most commonly used. Patients with extensive burn injuries have limited donor site availability. Meek micrografting is a well-known technique to enable larger expansions. A review was conducted on the outcomes of the Meek micrograft technique., Method: A database search in PubMed, Web of Science, Google Scholar and the Cochrane Library was conducted from the first Meek micrografting report in 1958 until 2021, including terms 'burns', 'micrografting' and/or 'Meek'. Original papers reporting outcomes of Meek micrografting were included., Results: 1529 papers were identified and eventually 15 articles were included, the majority classified as poor quality according to Chambers criteria. 310 patients with 56% mean TBSA were described. Weighted averages were calculated for 'graft take' 82 ± 7%, 'time to wound closure' 53 ± 20 days and 'length of hospital stay' 61 ± 31 days. Scar quality was minimally described and often poorly assessed. Limited data were available on outcomes 'donor site size', 'number of operations', 'cost effectiveness' and 'bacterial load/wound infection rate'., Conclusion: Overall poor study quality and the specific lack of data on scar quality, made it impossible to draw conclusions on the outcomes of Meek micrografting. A randomized controlled trial is required to further investigate the performance of the Meek micrograft technique., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Introduction: Early surgical debridement of the deep second and third-degree burns is still the standard of care (SOC) to prepare the wound bed for skin grafting. However, this technique has some drawbacks that explain the growing interest in enzymatic debridement as an alternative. In this article, we provide a historic overview as well as the current state-of-the-art and future prospective of this type of non-surgical debridement., Materials and Methods: A narrative review of the available literature was conducted using a systematic search., Results: A total of 32 articles were included. The only enzyme mixture still used nowadays for burn eschar removal is bromelain-based. There is increasing evidence that this type of enzymatic debridement is a powerful tool to selectively remove the eschar in deep burns, thereby reducing the need for autologous skin grafting compared to surgical SOC. Moreover, off-label use of enzymatic debridement with NexoBrid ® (facial, pediatric, and >15%TBSA burns) has proven to be effective and safe., Conclusion: There is increasing evidence that bedside administered NexoBrid ® , preferably under regional anesthesia, is a powerful tool for selective burn eschar removal. However, the clinical wound bed evaluation post-NexoBrid ® procedure in relation to the optimal treatment decision-conservative treatment vs. surgery-is not yet completely elucidated. More high-quality prospective clinical trials are necessary to compare enzymatic debridement of objectively confirmed deep burns with the current standard treatment and assess the effectiveness of the eschar removal, the need for surgery, the healing time of such wounds, and the long-term scar quality.

Background: Silicone products, either as a sheet or in fluid form, are universally considered as the first line therapy in the prevention and treatment of hypertrophic scars and keloids. However, the study results have been questioned by different authors and there has never been a large systematic synopsis published on the efficacy of fluid silicone gels. This systematic review aims to elucidate the available evidence of the results obtained by fluid silicone gels and present a complete and comprehensive overview of the available literature as well as a meta-analysis of the pooled data., Methods: A systematic search for articles concerning the use of silicone gel in the treatment and prevention of scars was performed on 3 different databases (Pubmed, Embase and Cochrane library) according to the PRISMA statement. Only RCT's were included. Qualitative assessment was done by 2 separate reviewers using the Cochrane risk of bias (RoB 2) assessment tool. Revman 5.4.1 software was used for meta-analysis., Results: The search yielded 507 articles. Two articles were identified through other sources. After deduplication and removal of ineligible records, 340 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 18 articles were included. A meta-analysis comparing fluid silicone gel to no treatment or placebo gels was conducted., Conclusion: Studies on the effects of liquid silicone gels on hypertrophic scars are numerous and this systematic review shows that the use of liquid silicone gels is associated with both a prophylactic and a curative effect on scars. However, a considerable amount of the available 'high evidence' trials are at a high risk for bias and it is uncertain whether or not the effects of silicone gels are comparable to silicone sheets and if the additional components present in many silicone gels are partially responsible for their scar improving capacity., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a low-AGE ( n = 20) or regular diabetic ( n = 20) diet group. A three-day meal questionnaire was used to estimate average quantity of dAGEs. AGE accumulation was measured using skin autofluorescence and urine spectroscopy. sRAGE (soluble receptor AGE) was quantified using ELISA. After 8 weeks, the mean consumption of dAGEs was considerably reduced, both in the low-AGE diet ( p = 0.004) and the control ( p = 0.019) group. The expected urinary emission peak at 490 nm was shifted to 520 nm in some spectra. dAGEs did not correspond with urine AGE output. An AGE-limited diet for two months did not affect AGE content in skin and urine, or sRAGE concentration in the blood. The role of glycemia is likely to be greater than the impact of dAGE consumption. The unique observation of a fluorescence pattern at 520 nm warrants further examination, since it might point to genetic differences in AGE regulation, which could have clinical consequences, as AGE content depends on its formation and elimination.

Introduction: Laser Doppler imaging is universally considered the most evidence-based method for objective burn depth assessment by accurately predicting burn wound healing potential. This study has analyzed how exactly laser Doppler imaging measurements can be useful in the early therapeutic decision making for patients with clinically indeterminate depth burns., Material and Methods: An extensive survey, by questionnaire and in-depth interviews, was conducted among 51 burn centers worldwide to gain insight on the practical use of laser Doppler imaging., Results: Twenty-seven (53%) of the 51 burn centers contacted almost completely answered the 32 questions. Fifty-two percent of these centers (14/27) had at least 10 years of laser Doppler imaging experience. laser Doppler imaging was considered to be mainly or almost completely accurate by 89%. In case of discrepancy between clinical assessment and LDI, 41% relied more on clinical diagnosis, 25% delayed decision to operate, while 16% re-scanned the next day. The centers most experienced with laser Doppler imaging (13%) relied on it more. Final decisions for treatment were based on the combination of laser Doppler imaging and clinical assessment by 74%. Seventy percent of the centers almost never operated burns with laser Doppler imaging-red and would almost always operate burns with LDI-blue. Treatment decisions for intermediate laser Doppler imaging colors (pink, yellow and green) varied, with 76% basing decisions on other factors: % Total Body Surface Area (TBSA), general health, age, location of the burn, potential for colonization/infection, patient preference, compliance with aftercare, logistics, and socio-economic factors., Conclusion: Laser Doppler imaging reduces the number of clinical indeterminate depth burns. For these intermediate depth burns on laser Doppler imaging, treatment decisions are based on a combination of interpretation ('man') and laser Doppler imaging measurements ('machine'). Thorough knowledge of confounding factors and validated laser Doppler imaging color code, consideration of surrounding laser Doppler imaging colors, the use of mean flux values, and not directly burn related factors are essential. Burn centers with most laser Doppler imaging experience considered laser Doppler imaging an indispensable diagnostic tool., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: Laser Doppler imaging (LDI) is still not an ubiquitous part of burn care worldwide despite reported accuracy rates of more than 95%, which is significantly higher than clinical assessment alone (50-75%). The aims of Part I of this survey study are: to identify the most important barriers for the use of LDI and to provide useful recommendations for efficient implementation in routine burn care. The actual interpretation and use of LDI measurements is discussed in the Enigma Part II article., Material and Methods: 1. Informative interviews with 15 representatives of burn centers without LDI. 2. A survey among 51 burn centers with LDI by means of an extensive questionnaire. 3. In-depth interviews with 21 of the participating centers., Results: 1. All 15 centers without LDI indicated that cost of purchase in combination with maintenance of the LDI device, as well as personnel costs were the reason for not buying, while 12 (80%) also rated the current scientific evidence as insufficient. 2. Twenty-seven burn centers with an LDI (53%) participated and filled in almost the entire questionnaire. In 5 centers, cost delayed the purchase of LDI. The hospital/department paid for the LDI device in 62% of the burn centers and in 88% also for maintenance and salaries. The LDI operators were mainly surgeons (47%) or nurses (42%). In more than half of the burn centers (52%), between 2 and 5 people were trained and certified to use an LDI. In 50% of burn centers, the interpretation of the LDI scan was done by the same person doing the actual measurements. Eighty-nine percent of the burn centers considered the accuracy of the LDI scan as mainly to almost completely accurate. In case of real discrepancy between clinical diagnosis and LDI, in 48% of the burn centers (13/27) the surgeon still relied more on the clinical diagnosis despite reporting this high or almost complete accuracy rate of the LDI., Conclusions: Barriers for the routine implementation of LDI were: 1. cost of purchasing and using an LDI combined with health care systems that inadequately reimburse non-surgical management; 2. lack of awareness of or ongoing skepticism towards the scientific evidence supporting LDI use; and 3. organizational constraints combined with logistical limitations. Our recommendations for wider use of LDI technology include: 1. a cost-effective reimbursement of LDI use combined with a more appropriate valuation of expert conservative management compared to surgical therapy; 2. increased use of LDI for every mixed depth burn and; 3. specialized LDI teams to improve burn procedural flexibility and to enable embedding LDI use in the burn care routine. Implementing these measures would promote the highest standards for LDI measurements and interpretation resulting in optimal care with mutual benefits for the hospital, for burn care teams and, most importantly, for the patients., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Early clinical assessment of burn depth and associated healing potential (HP) remains extremely challenging, even for experienced surgeons. Inaccurate diagnosis often leads to prolonged healing times and unnecessary surgical procedures, resulting in incremental costs, and unfavorable outcomes. Laser Doppler imaging (LDI) is currently the most objective and accurate diagnostic tool to measure blood flow and its associated HP, the main predictor for a patient's long-term functional and aesthetic outcome. A systematic review was performed on non-invasive, laser-based methods for burn depth assessment using skin microcirculation measurements to determine time to healing: Laser Doppler flowmetry (LDF), LDI and laser speckle contrast imaging (LSCI). Important drawbacks of single point LDF measurements are direct contact with numerous small points on the wound bed and the need to carry out serial measurements over several days. LDI is a fast, "non-contact," single measurement tool allowing to scan large burned areas with a 96% accuracy. LDI reduces the number of surgeries, improves the functional and aesthetic outcome and is cost-effective. There is only limited evidence for the use of LSCI in burn depth assessment. LSCI still needs technical improvements and scientific validation, before it can be approved for reliable burn assessment. LDI has proven to be invaluable in determining the optimal treatment of a burn patient. For unclear reasons, LDI is still not routinely used in burn centers worldwide. Additional research is required to identify potential "barriers" for universal implementation of this evidence-based burn depth assessment tool., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)