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Background: Spina bifida cystica (SB) is one of the most common neural tube defects affecting 1 in 2,500 newborns worldwide. Due to the neurological deficits associated with SB, injuries from thermal exposure, trauma, or other etiology may be more severe rendering their treatment a challenge for a traditional approach to burn and wound management. Despite this relatively high disease incidence rate, few studies exist to evaluate wound development or the natural history of wound healing in patients with SB. Case presentation: We present a case of a pediatric patient with a history of SB who sustained a full thickness burn to the right plantar foot in February of 2023. The 8-year-old was riding an all-terrain vehicle when his right foot made contact with the hot tailpipe. The insensate neuropathy associated with the patient’s SB contributed to the extreme severity of thermal contact injury. We report the burn, treatments, the usage of a novel dermal replacement, and outcomes of this case. Conclusion: This case demonstrates successful limb salvage in a pediatric patient with severe plantar foot burns utilizing a novel collagen-elastin dermal matrix for tissue reconstruction. Limb salvage was the preferred treatment option over amputation and a prosthetic considering the patient’s age and need for future prostheses. Given the severity of the burn, the impaired wound healing due to his baseline neuropathy, and his baseline ambulatory status, the optimal outcome in this case was limb salvage, which was successfully achieved.

Background: This prospective study aimed to evaluate the outcomes of the use of dermal templates for lengthy volar soft tissue defects (1.5-4 cm) in the fingers., Methods: The volar soft tissue defects of 15 patients (19 fingers) were treated with Lando dermal template coverage between June 2022 and November 2022. We evaluated sensory recovery, scar formation, and overall appearance of the repair site at an average of 13 months (range, 12-17 months) of follow-up., Results: The defect healed in all cases. We found an average static 2-point discrimination of 7 mm (range 4 to 14 mm). Scar formation was evident in all cases. The repair did not restore the bulkiness of the volar finger, especially in the finger with the bony exposure. Nail deformities and joint contracture were observed in some cases., Conclusion: Dermal template repair does not restore normal sensation and inevitably leads to scar formation when the defect is longer (>1.5 cm). Bulkiness of the volar finger is not restored in most patients, especially when there was bone or tendon exposure in the initial wound site., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model., Methods: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 µg ‧ cm -2 . The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale., Results: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres., Conclusion: The formation of scars with the best elasticity was exhibited by addition 1.0 µg ‧ cm -2 of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Objective: The clinical effects of artificial dermis in treating skin and soft tissue defects accompanied by bone or tendon exposure were assessed., Approach: A retrospective analysis was conducted on the clinical data of 45 cases of skin and soft tissue defects accompanied by bone or tendon exposure admitted to the trauma surgery department of Fujian Provincial Hospital between February 2018 and August 2020. They were divided into the artificial dermis and control groups. The wound was assessed using the Vancouver Scar Scale (mVSS), and the postoperative visual analogue scale (VAS) scores were recorded at 3, 6, 9, and 12 months after surgery. At the 12-month after surgery, skin sensation recovery was evaluated using the criteria of the British Medical Research Council (BMRC)., Results: The cases included 26 males and 19 females, aged 50 to 85 years. All patients were followed up for an average of 13.8 months (range: 12-18 months). Compared with controls, the wound healing time of the observation group was longer (35.8 ± 10.6 vs. 28.5 ± 4.8, P = 0.007), without significant differences for the number of operations and length of hospitalization. The mVSS scores were not different between groups (P group = 0.294), but the scores decreased with time (P time < 0.001), and the group×time interaction was significant (P interaction < 0.001). Similarly, the VAS scores were not different between groups (P group = 0.667), but the scores decreased with time (P time < 0.001); the group×time interaction was not significant (P interaction = 0.274). At the 12-month mark following the operation, in the artificial dermis group, the MCRR score was S3+ in 23 patients, while it ranged from S0 to S3 in two patients; in the control group, S3+ was observed in 17 patients, and S0-S3 in three (P = 0.815)., Conclusion: Artificial dermis treatment is considered a safe and effective alternative therapy for patients with skin and soft tissue defects accompanied by bone or tendon exposure who cannot tolerate or are unwilling to undergo autologous skin flap transplantation. It offers the advantages of minimal donor site trauma, simplicity in operation, and favorable postoperative functional recovery., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Extensive full-thickness soft-tissue defects remain a challenge in reconstructive surgery. NovoSorb® Biodegradable Temporising Matrix (BTM) represents a novel dermal substitute and was evaluated in wounds deriving from different aetiologies and to highlight risk factors for poor take rates., Methods: All patients treated with BTM at our department between March 2020 and October 2022 were included. Differences in univariate and linear regression models identified predictors and risk factors for take rates of BTM and split-thickness skin grafts (STSG)., Results: Three hundred patients (mean age 54.2 ± 20.1 years, 66.3% male, 59.7% burns, 19.7% trauma and 20.6% others) were evaluated. Mean take rates of BTM and STSG after BTM delamination were 82.7 ± 25.2% and 86.0 ± 22.6%, respectively. Multiple regression analyses showed that higher body mass index (BMI, OR 0.43, 95% CI 0.86, -0.01, p = 0.44), prior allograft transplantation (OR 15.12, 95% CI 26.98, -3.31, p = 0.041), longer trauma-to-BTM-application intervals (OR 0.01, 95% CI 0.001, -0.001, p = 0.038), positive wound swabs before BTM (OR 7.15, 95% CI 13.50, -0.80, p = 0.028) and peripheral artery disease (OR 10.80, 95% CI 18.63, -2.96, p = 0.007) were associated with poorer BTM take. Higher BMI (OR 0.40, 95% CI 0.76, -0.08, p = 0.026), increasing BTM graft surface areas (OR 0.58, 95% CI -1.00, -0.17, p = 0.005), prior allograft (OR 12.20, 95% CI -21.99, -2.41, p = 0.015) or autograft transplantations (OR 22.42, 95% CI 38.69, -6.14, p = 0.001), tumour as the aetiology of the wound (OR 37.42, 95% CI 57.41, -17.83, p = 0.001), diabetes (OR 6.64, 95% CI 12.80, -0.48, p = 0.035) and impaired kidney function (OR 5.90, 95% CI 10.94, -0.86, p = 0.021) were associated with poorer STSG take after delamination of BTM, whereas higher BTM take rates were associated with better STSG take (OR 0.40, 95% CI 0.31,0.50, p < 0.001)., Conclusion: Extensive complex wounds of different aetiologies unsuitable for immediate STSG can be successfully reconstructed by means of two-staged BTM application and subsequent skin grafting. Importantly, presence of wound contamination or infection and prior allograft coverage appear to jeopardise good BTM and STSG take., (Copyright © 2024. Published by Elsevier Ltd.)

Full-thickness wounds are severe cutaneous damages with destroyed self-healing function, which need efficient clinical interventions. Inspired by the hierarchical structure of natural skin, we have for the first time developed a biomimetic tri-layered artificial skin (TLAS) comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing. The TLAS with the thickness of 3-7 mm displays a hierarchical nanostructure consisting of the top homogeneous silica gel film, the middle compact collagen membrane, and the bottom porous collagen scaffold, exquisitely mimicking the epidermis, basement membrane and dermis of natural skin, respectively. The 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide-dehydrothermal (EDC/NHS-DHT) dual-crosslinked collagen composite bilayer, with a crosslinking degree of 79.5 %, displays remarkable biocompatibility, bioactivity, and biosafety with no risk of hemolysis and pyrogen reactions. Notably, the extra collagen membrane layer provides a robust barrier to block the penetration of silica gel into the collagen porous scaffold, leading to the TLAS with enhanced biocompatibility and bioactivity. The full-thickness wound rat model studies have indicated the TLAS significantly facilitates the regeneration of full-thickness defects by accelerating re-epithelization, collagen deposition and migration of skin appendages. The highly biocompatible and bioactive tri-layered artificial skin provides an improved treatment for full-thickness wounds, which has great potential in tissue engineering., 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 © 2024 Elsevier B.V. All rights reserved.)

Skin substitutes are designed to promote wound healing by replacing extracellular matrix. Silk-elastin-like protein is a renewable extracellular matrix-like material that integrated the advantages of silk and elastin-like protein. In this study, electrospun silk-elastin-like protein (SELP) nanofiber membrane covered with bacterial cellulose (BC) was created as a potential skin substitute to mimic gradient structure of epidermis and dermis of skin. The two layers were glued together using adhesive SELP containing 3,4-dihydroxyphenylalanine (DOPA) converted from tyrosine by tyrosinase. Skin topical drugs commonly used in clinical practice can penetrate through the SELP/BC barrier, and the rate of penetration is proportional to drug concentration. BC with dense fibrous structure can act as a barrier to preserve the inner SELP layer and prevent bacterial invasion, with a blocking permeation efficiency over 99% against four species of bacteria. Cell experiments demonstrated that the reticular fibers of SELP could provide an appropriate growth environment for skin cells proliferation and adhesion, which is considered to promote tissue repair and regeneration. The promising results support this strategy to fabricate a silk-elastin-like protein-based biomaterial for skin substitutes in the clinical treatment of full skin injuries and ulcers., 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 © 2023 Elsevier B.V. All rights reserved.)

An optimal tissue-engineered dermal substitute should possess biocompatibility and cell adhesion conduction to facilitate fibroblast and keratinocyte infiltration and proliferation, as well as angiogenesis potential to escalate wound healing. Zinc was doped to bioactive glass-ceramic (Zn-BGC) to promote biocompatibility and angiogenesis properties. Zn-BGC was then incorporated into a collagen (Col) and gelatin (Gel) porous scaffold. The bioactive porous bionanocomposite exhibited biocompatibility along with improved cell attachment and proliferation. Scaffolds including Col-Gel/Zn-BGC with or without mouse embryonic fibroblasts were applied on full-thickness skin wounds on the BALB/c mice to assess their wound healing potential in vivo. The results indicated that the biodegradation rate of the Col-Gel/Zn-BGC nanocomposites was comparable to the rate of skin tissue regeneration in vivo. Macroscopic wound healing results showed that Col-Gel/Zn-BGC loaded with mouse embryonic fibroblast possesses the smallest wound size, indicating the fastest healing process. Histopathological evaluations displayed that the optimal wound regeneration was observed in Col-Gel/Zn-BGC nanocomposites loaded with mouse embryonic fibroblasts indicated by epithelialization and angiogenesis; besides the number of fibroblasts and hair follicles was increased. The bioactive nanocomposite scaffold of Col-Gel containing Zn-BGC nanoparticles loaded with mouse embryonic fibroblasts can be employed as a desirable skin substitute to ameliorate cutaneous wound regeneration., 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 © 2023. Published by Elsevier B.V.)

As a promising treatment for third-degree burns, grafting with bioengineering skin substitutes shows a capability to overcome the deficiency of donor skin. Similar mechanical properties with human skin are required for employed skin substitutes to avoid secondary damage to patients. Given the representativeness of orthotropy in mechanical properties, there is a need for developing orthotropic skin substitutes. This paper presents computational investigation as well as structural design for the fabrication of orthotropic skin substitutes. A finite element method (FEM) based mechanics simulation model for analyzing the stress field in the skin substitute was developed, by which the stress distribution in mimetic structures of the epidermis and dermis can be acquired. Moreover, the equation of Young's modulus was deduced based on the simulation result, which expressed the mechanical property of designed skin substitutes. Furthermore, several structures of skin substitutes were proposed and their calculated Young's modulus ranged from 21.87 kPa to 213.32 kPa, which was similar to the human skin. Ultimately, uniaxial tensile tests were performed for three types of 3D-printed orthotropic skin substitutes, which validates the feasibility to regulate Young's modulus by regulating the structure of fabricated skin substitutes., 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 © 2023 Elsevier Ltd. All rights reserved.)

Aim: Oxygen is required for cell migration into the scaffold and for the survival of the overlying graft in the use of a single-layer scaffold. In the absence of diffusion from the avascular wound base, such as in areas above the bone/tendon, oxygen delivery from the lateral edges of the scaffold is important. This study compared the oxygen permeability of skin scaffolds, currently commercially available in Turkey (Nevelia®, MatriDerm®, and Pelnac®), in the lateral plane., Materials and Methods: To measure oxygen permeability, an interconnected closed system was created. Oxygen permeability was evaluated based on the color change that occurred as a result of the reaction of iron with oxygen. After the dermal matrices placed in the closed system were exposed to oxygen, the color change on the surface of the dermal matrices was measured, and electron microscopic images were recorded to compare deformation before and after the procedure., Results: Two scaffolds did not show deformation after the procedure while Pelnac® had minimal deformation. The oxygen rates on the nitrogen side of the test apparatus were found to be 29%, 34%, and 27% for Nevelia®, MatriDerm®, and Pelnac®, respectively; and the oxygen transmission lengths (length of color change) of these scaffolds in the lateral plane were 1, 2, and 0.5 cm, respectively., Conclusion: Although none of the scaffolds showed significant deformation, and all continued to exhibit their scaffold properties after the procedure, MatriDerm® was determined to be the most suitable scaffold for use in avascular areas, with a 2-cm oxygen transmission length in terms of lateral oxygenation., 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 © 2023 Elsevier Ltd and ISBI. All rights reserved.)

We present our results of one-stage resurfacing following syndactyly release with the Pelnac™ artificial dermal substitute. From 2016 to 2020, raw areas after digit release were restored with an artificial dermal substitute in 145 webs from 62 patients (average age, 33.1 months) including 65 simple incomplete web spaces, 29 simple complete web spaces, 20 complex complete web spaces, and 31 complex complicated web spaces. Fourteen patients were syndromic. The average follow-up period was 33.4 months (range, 7-55 months). Postoperative outcomes assessed as according to the Vancouver scar scale (0-14) averaged 1.8 (range, 0-11) and web creep score (0-5) averaged 0.7 (range, 0-4). Patient- and family-provided visual analog scale scores averaged 1.1 (range, 0-10) for appearance. In conclusion, the Pelnac™ artificial dermal substitute is a minimally invasive, simple, and effective option for one-stage resurfacing of defects in syndactyly release., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Patients with deep and extensive wounds need urgent skin coverage to re-establish the cutaneous barrier that prevents life-threatening infections and dehydration. However, the current clinically-available skin substitutes intended for permanent coverage are limited in number, and a trade-off between production time and quality must be made. Here, we report the use of decellularized self-assembled dermal matrices to reduce by half the manufacturing process time of clinical-grade skin substitutes. These decellularized matrices can be stored for over 18 months and recellularized with patients' cells in order to generate skin substitutes that show outstanding histological and mechanical properties in vitro. Once grafted in mice, these substitutes persist over weeks with high graft take, few contraction events, and high stem cell content. These next-generation skin substitutes constitute a substantial advancement in the treatment of major burn patients, combining, for the first time, high functionality, rapid manufacturability and easy handling for surgeons and healthcare practitioners. Future clinical trials will be conducted to assess the advantages of these substitutes over existing treatments. STATEMENT OF SIGNIFICANCE: The number of patients in need for organ transplantation is ever-growing and there is a shortage in tissue and organ donors. In this study, we show for the first time that we can preserve decellularized self-assembled tissues and keep them in storage. Then, in only three weeks we can use them to produce bilayered skin substitutes that have properties very close to those of the native human skin. These findings therefore represent a major step forward in the field of tissue engineering and organ transplantation, paving the way toward a universal off-the-shelf biomaterial for tissue reconstruction and surgery that will be beneficial for many clinicians and patients., 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 © 2023. Published by Elsevier Ltd.)

Dermal exposure to metal(loid)s from contaminated soils can contribute to health risk. Metal(loid) speciation will influence their bioaccessibility in sweat and subsequent permeation across the skin. Therefore, the speciation of the bioaccessible fraction of metal(loid)s in two synthetic sweat formulations (sweat A (pH 6.5) and B (pH 4.7)) was assessed using chemical equilibrium modelling (Visual MINTEQ). Permeation through synthetic skin and the influence of sebum in the permeation of As, Cr, Cu, Ni, Pb, and Zn were also investigated using Franz cells. Following dermal bioaccessibility tests for five Chromated Copper Arsenate (CCA)-contaminated soils and one certified soil (SQC001), mean metal(loid) bioaccessibility (%) was higher in sweat B (2.33-18.8) compared to sweat A (0.12-7.53). Arsenic was almost entirely found as As(V) in both sweats. In sweat A, comparable concentrations of Cr(III) and Cr(VI) were found whereas in sweat B, Cr was primarily present as Cr(III). Copper was primarily found as Cu 2+ . Bioaccessible Cr extracted from nearly all soils permeated through the Strat-M membrane when it was coated with sebum. The Cr permeation coefficient (K p ) ranged between 0.004 and 0.13 cm/h and the Kp for Cu was higher (0.024-0.52 cm/h). As, Ni, Pb, and Zn did not permeate the synthetic skin., 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 © 2023 Elsevier B.V. All rights reserved.)

A three-dimensional (3D) artificial skin model offers diverse platforms for skin transplantation, disease mechanisms, and biomaterial testing for skin tissue. However, implementing physiological complexes such as the neurovascular system with living cells in this stratified structure is extremely difficult. In this study, full-thickness skin models were fabricated from methacrylated silk fibroin (Silk-GMA) and gelatin (Gel-GMA) seeded with keratinocytes, fibroblasts, and vascular endothelial cells representing the epidermis and dermis layers through a digital light processing (DLP) 3D printer. Printability, mechanical properties, and cell viability of the skin hydrogels fabricated with different concentrations of Silk-GMA and Gel-GMA were analyzed to find the optimal concentrations for the 3D printing of the artificial skin model. After the skin model was DLP-3D printed using Gel-GMA 15% + Silk-GMA 5% bioink, cultured, and air-lifted for four weeks, well-proliferated keratinocytes and fibroblasts were observed in histological analysis, and increased expressions of Cytokeratin 13, Phalloidin, and CD31 were noted in immunofluorescence staining. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound-healing capabilities of the skin hydrogel. When the epidermal growth factor (EGF) was applied, enhanced wound healing in the epidermis and dermis layer with the proliferation of keratinocytes and fibroblasts was observed. Also, the semi-quantitative reverse transcription-polymerase chain reaction revealed increased expression of Cytokeratin 13, fibroblast growth factor, and CD31 in the EGF-treated group relative to the control group. The DLP 3D-printed artificial skin model was mechanically stable and biocompatible for more than four weeks, demonstrating the potential for application in skin tissue engineering. STATEMENT OF SIGNIFICANCE: A full-thickness artificial skin model was 3D-printed in this study with a digital light processing technique using silk fibroin and gelatin, which mimics the structural and cellular compositions of the human skin. The 3D-printed skin hydrogel ensured the viability of the cells in the skin layers that proliferated well after air-lifting cultivation, shown in the histological analysis and immunofluorescence stainings. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound healing capabilities of the skin hydrogel, which demonstrated enhanced wound healing in the epidermis and dermis layer with the application of epidermal growth factor on the wound compared to the control. The bioengineered hydrogel expands the applicability of artificial skin models for skin substitutes, wound models, and drug testing., 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 © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Electrochemical immunosensors coupled with reverse iontophoresis (RI) for noninvasive determination of cardiac troponins were developed and validated according to ICH Q2 (R1) guideline. Linearity was in 0.01-10 and 100-500 ng/mL ranges. LODs (ng/mL) were in 6-25 × 10-4, while LOQs (μg/mL) were in 18-7.5 × 10-4 range. Chemometric evaluation was performed on raw data simply by principle component analysis and cluster analysis to discriminate stages of immunosensors. This is the first demonstration of RI determination of cardiac troponins so far. Findings of the current manuscript have great potential to develop point of care diagnostic systems for major cardiac events, where high sensitivity and specificity are required., 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 © 2023 Elsevier B.V. All rights reserved.)

Skin substitutes are designed dressings intended to promote wound closure. In previous in vitro and in vivo studies on small animal, an acellular skin patch made of collagen hydrogel with dermal fibroblast conditioned medium (Col-DFCM), a collagen sponge scaffold with freshly harvested skin cells (OTC), and a platelet-rich-plasma gel with freshly harvested skin cells (PRP) have been developed and tested for immediate treatment of full-thickness wound. However, to determine the safety and efficacy of these skin patches for clinical applications, further study in a large animal model is needed. The aim of this study is to evaluate the potential of Col-DFCM, OTC and PRP in treating full-thickness wound in an ovine model via histological analysis and immunohistochemistry staining were performed, with the untreated (NT) group serving as the control. Gross examination was conducted on day 7, 14 and 21 to determine the wound closure rate. The findings of percentage of wound size reduction showed that the wound healed fastest in the presence of Col-DFCM (91.34 ± 23.35%) followed by OTC (84.49 ± 23.13%), PRP (77.73 ± 20.9%) and NT group (73.94 ± 23.71%). Histological evaluation with Hematoxylin & Eosin (H & E) and Masson's trichrome staining was used to study the structure of the wound area. The results showed that OTC treated wound was more mature as indicated by the presence of a thinner epidermis followed by the Col-DFCM, PRP and NT group. Immunohistochemistry analysis also confirmed the integrity and maturity of the regenerated skin, with positive expression of cytokeratin 10 (CK10) and involucrin in the epidermal layer. In conclusion, Col-DFCM, OTC and PRP treatments promote healing of full-thickness wound and have the potential to be used clinically for rapid treatment of full-thickness wound., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: For extensive burns, autologous donor skin may be insufficient for early debridement and grafting in a single stage. A novel, synthetic polyurethane dermal template (NovoSorb® Biodegradable Temporising Matrix, BTM) was developed to address this need. The aim of this study was to evaluate use of BTM for primary dermal repair after deep burn injury., Methods: A multicentre, prospective, clinical study was conducted from September 2015 to May 2018. The primary endpoint was % split skin graft take over applied BTM at 7-10 days after grafting. Secondary endpoints included % BTM take, incidence of infection and adverse events, and scar quality to 12 months after BTM application., Results: Thirty patients were treated with BTM and delayed split skin grafting. The % graft take had a mean of 81.9% and % BTM take had a mean of 88.6%, demonstrating effective integration of BTM. When managed appropriately, it was possible for BTM to integrate successfully despite findings suggestive of infection. Scar quality improved over time., Discussion: These results provide additional clinical evidence on the safety and performance of BTM as an effective dermal substitute in the treatment of patients with deep burn injuries., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cold Atmospheric Plasma (CAP) is an emerging physical approach displaying encouraging antitumor and wound healing effects both in vitro and in vivo. In this study, we assessed the potential of direct CAP to remodel skin collagens using an original tissue-engineered human dermal substitute model rich in endogenous extracellular matrix (ECM) covered with 600 µl of culture medium and treated with CAP for 30 and 120 s. Our results indicated that Reactive Oxygen and Nitrogen Species (RONS) such as H 2 O 2 , NO 3 - and NO 2 - were produced in the medium during treatment. It appeared that in the CAP-treated dermal substitutes 1) cell viability was not altered, 2) pro-collagen I secretion was not modified over 48 h of culture after treatment, 3) global activity of matrix metalloproteinases MMPs was not modulated over 48 h after treatment, and 4) no change in hydroxyproline content was observed over 5 days after treatment. In order to confirm the efficiency of our device, we showed that the plasma-activated culture medium induced cell apoptosis and growth delay using a 3D human tumor spheroid model. In conclusion, no effect of direct CAP treatment was monitored on dermal ECM production and degradation, indicating that CAP does not stimulate collagen remodeling at the tissue scale., 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 © 2021 Elsevier B.V. All rights reserved.)

As an organ in direct contact with the external environment, the skin is the first line of defense against external stimuli, so it is the most vulnerable to damage. In addition, there is an increasing demand for artificial skin in the fields of drug testing, disease research and cosmetic testing. Traditional skin tissue engineering has made encouraging progress after years of development. However, due to the complexity of the skin structures, there is still a big gap between existing artificial skin and natural skin in terms of function. Three-dimensional (3D) bioprinting is an advanced biological manufacturing method. It accurately deposits bioinks into pre-designed three-dimensional shapes to create complex biological tissues. This technology aims to print artificial tissues and organs with biological activities and complete physiological functions, thereby alleviating the problem of tissues and organs in short supply. Here, based on the introduction to skin structure and function, we systematically elaborate and analyze skin manufacturing methods, 3D bioprinting biomaterials and strategies, etc. Finally, the challenges and perspectives in 3D bioprinting skin field are summarized., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Scalp wounds pose reconstructive challenges due to the lack of skin elasticity, potential for compromised adjacent tissue, and desire for the restoration of esthetic contour. Bilayer Wound Matrix (BWM) has been successfully employed as a treatment modality for complex, full-thickness wounds of the scalp. We aimed to highlight risk factors for BWM success and failure in complex wounds of the scalp., Methods: A retrospective case-control study was performed from 2012 to 2019 of adult subjects who presented to plastic or dermatological surgery with complex scalp defects with or without exposed calvarium, who underwent staged reconstruction with BWM and split-thickness skin grafting or secondary intention. Success was defined as complete wound re-epithelialization within 90-day follow-up without additional operative procedures for wound coverage. Demographics, comorbidities, treatment history, wound characteristics, and clinical course were analyzed and correlated with reconstructive outcomes., Results: In total, 127 subjects were identified for inclusion, with mean age 74.6 ± 12.2 years, defect area 80.2 ± 89.4 cm 2 , and wound age 10.0 ± 65.4 days. Successful wound reconstruction occurred in 107 (84%) subjects. Postoperative wound infections were an independent predictor of BWM failure at 90 days (Odds Ratio: 6.4, 95% Confidence Interval: 1.5 - 26.7, and p<0.012). Additionally, subjects who underwent preoperative radiation were more likely to suffer from reconstructive failure (p<0.040) as well as those who require postoperative inpatient admission (p<0.034)., Conclusion: BWM represents a reliable and efficacious modality in the treatment of complex scalp wounds. Patient comorbidities may not heavily influence the success of BWM to establish adequate wound coverage; however, preoperative radiation and postoperative wound infection may often lead to reconstructive failure., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Biofabrication of skin tissue equivalents using 3D bioprinting technology has gained much attention in recent times due to the simplicity, the versatility of the technology and its ability in bioengineering biomimetic tissue histology. The key component being the bioink, several groups are actively working on the development of various bioink formulations for optimal skin tissue construction., Methods: Here, we present alginate (ALG), gelatin (GEL) and diethylaminoethyl cellulose (DCEL) based bioink formulation and its application in bioprinting and biofabrication of skin tissue equivalents. Briefly, DEAE cellulose powder was dispersed in alginate solution with constant stirring at 60 °C to obtain a uniform distribution of cellulose fibers; this was then mixed with GEL solution to prepare the bioink. The formulation was systematically characterized for its morphological, physical, chemical, rheological, biodegradation and biocompatibility properties. The printability, shape fidelity and cell-laden printing were assessed using the CellInk bioprinter., Results: The bioink proved to be a good printable, non-cytotoxic and stable hydrogel formulation. The primary human fibroblast and keratinocyte-loaded 3D bioprinted constructs showed excellent cell viability, collagen synthesis, skin-specific marker and biomimetic tissue histology., Conclusion: The results demonstrated the successful formulation of ALG-GEL-DCEL bioink and its application in the development of human skin tissue equivalents with distinct epidermal-dermal histological features., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Severe injuries to skin including hypodermis require full-thickness skin replacement. Here, we bioengineered a tri-layered human skin substitute (TLSS) containing the epidermis, dermis, and hypodermis. The hypodermal layer was generated by differentiation of human adipose stem cells (ASC) in a collagen type I hydrogel and combined with a prevascularized dermis consisting of human dermal microvascular endothelial cells and fibroblasts, which arranged into a dense vascular network. Subsequently, keratinocytes were seeded on top to generate the epidermal layer of the TLSS. The differentiation of ASC into adipocytes was confirmed in vitro on the mRNA level by the presence of adiponectin, as well as by the expression of perilipin and FABP-4 proteins. Moreover, functional characteristics of the hypodermis in vitro and in vivo were evaluated by Oil Red O, BODIPY, and AdipoRed stainings visualizing intracellular lipid droplets. Further, we demonstrated that both undifferentiated ASC and mature adipocytes present in the hypodermis influenced the keratinocyte maturation and homeostasis in the skin substitutes after transplantation. In particular, an enhanced secretion of TGF-β1 by these cells affected the epidermal morphogenesis as assessed by the expression of key proteins involved in the epidermal differentiation including cytokeratin 1, 10, 19 and cornified envelope formation such as involucrin. Here, we propose a novel functional hypodermal-dermo-epidermal tri-layered skin substitute containing blood capillaries that efficiently promote regeneration of skin defects. STATEMENT OF SIGNIFICANCE: The main objective of this study was to develop and assess the usefulness of a tri-layered human prevascularized skin substitute (TLSS) containing an epidermis, dermis, and hypodermis. The bioengineered hypodermis was generated from human adipose mesenchymal stem cells (ASC) and combined with a prevascularized dermis and epidermis. The TLSS represents an exceptional model for studying the role of cell-cell and cell-matrix interactions in vitro and in vivo. In particular, we observed that enhanced secretion of TGF-β1 in the hypodermis exerted a profound impact on fibroblast and keratinocyte differentiation, as well as epidermal barrier formation and homeostasis. Therefore, improved understanding of the cell-cell interactions in such a physiological skin model is essential to gain insights into different aspects of wound healing., 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 © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human plasma-derived bilayered skin substitutes have been successfully used by our group in different skin tissue engineering applications. However, several issues associated with their poor mechanical properties were observed, and they often resulted in rapid contraction and degradation. In this sense, hydrogels composed of plasma-derived fibrin and thiolated-hyaluronic acid (HA-SH, 0.05-0.2% w/v) crosslinked with poly(ethylene glycol) diacrylate (PEGDA, 2:1, 6:1, 10:1 and 14:1 mol of thiol to moles of acrylate) were developed to reduce the shrinking rates and enhance the mechanical properties of the plasma-derived matrices. Plasma/HA-SH-PEGDA hydrogels showed a decrease in the contraction behaviour ranging from 5% to 25% and an increase in Young's modulus. Furthermore, the results showed that a minimal amount of the added HA-SH was able to escape the plasma/HA-SH-PEGDA hydrogels after incubation in PBS. The results showed that the increase in rigidity of the matrices as well as the absence of adhesion cellular moieties in the second network of HA-SH/PEGDA, resulted in a decrease in contraction in the presence of the encapsulated primary human fibroblasts (hFBs), which may have been related to an overall decrease in proliferation of hFBs found for all hydrogels after 7 days with respect to the plasma control. The metabolic activity of hFB returned to the control levels at 14 days except for the 2:1 PEGDA crosslinking ratio. The metabolic activity of primary human keratinocytes (hKCs) seeded on the hydrogels showed a decrease when high amounts of HA-SH and PEGDA crosslinker were incorporated. Organotypic skins formed in vitro after 21 days with plasma/HA-SH-PEGDA hydrogels with an HA content of 0.05% w/v and a 2:1 crosslinking ratio were up to three times thicker than the plasma controls, evidencing a reduction in contraction, while they also showed better and more homogeneous keratin 10 (K10) expression in the supra-basal layer of the epidermis. Furthermore, filaggrin expression showed the formation of an enhanced stratum corneum for the constructs containing HA. These promising results indicate the potential of using these biomimetic hydrogels as in vitro skin models for pharmaceutical products and cosmetics and future work will elucidate their potential functionality for clinical treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acellular Dermal Matrix (ADM) is mainly made with human or porcine skins and has the risk of zoonotic virus transmission. The fish skin-derived ADM could overcome the shortcoming. Fish skin acellular matrix has been used as wound dressing, but there is few systematic studies on tilapia-skin acellular dermal matrix (TS-ADM). In the present study, a novel TS-ADM was made by an alkaline decellularization process and γ-irradiation. The physical properties, biocompatibility, pre-clinical safety and wound healing activity of TS-ADM were systematically evaluated for its value as a functionally bioactive wound dressing. Histopathological analysis (hematoxylin and eosin staining, 4,6-diamidino-2-phenylindole (DAPI) staining) and DNA quantification both proved that the nuclear components of tilapia skin were removed sufficiently in TS-ADM. Compared to the commercial porcine acellular dermal matrix (DC-ADM), TS-ADM has distinctive features in morphology, thermal stability, degradability and water vapor transmission. TS-ADM was more readily degradable than DC-ADM in vitro and in vivo. In both rat and mini-pig skin wound healing experiments, TS-ADM was shown to significantly promote granulation growth, collagen deposition, angiogenesis and re-epithelialization, which may be attributed to the high expression of transforming growth factor-beta 1 (TGF-β1), alpha-smooth muscle actin (α-SMA) and CD31. Herein, the novel TS-ADM, used as a low-cost bioactive dressing, could form a microenvironment conducive to wound healing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to investigate and develop range of motion (ROM) and mobilisation guidelines in adult patients where a newly developed synthetic dermal substitute was applied in our adult burn centre., Method: A retrospective case note audit was conducted on the first 20 acute burn injured patients who had a synthetic dermal substitute applied. Data collected included days to commencement of ROM, days to clearance for mobilisation, and joint ROM achieved after dermal substitute application (prior to delamination) and after split skin grafting (SSG) for the elbow, knee and shoulder joints. Scar assessments were completed at 12 months after injury using two scar assessment scales., Results: Clearance to mobilise occurred at mean 10.4 and 4.9 days after dermal substitute and after skin graft application to lower limbs respectively. ROM commenced at a mean of 9.9 (upper limbs) and 12.7 (lower limbs) days after dermal substitute application. Following skin grafting, ROM commenced at a mean of 6.6 and 6.5 days for upper limbs and lower limbs respectively. Prior to dermal substitute delamination mean flexion at the knee (86.3°), elbow (114.0°) and shoulder (143.4°) was achieved. Mean ROM continued to improve after grafting with knee (133.2°), elbow (126.1°) and shoulder (151.0°) flexion approaching normal ROM in most cases. Mean extension of the elbow (-4.6°) was maintained close to normal levels after skin grafting. There were no recorded instances of knee extension contracture. Patient and Observer Scar Assessment Scale and Matching Assessment of Photographs of Scars scores indicated good cosmetic outcomes with relatively low levels of itch and minimal pain reported at 12 months after injury., Conclusion: A steep learning curve was encountered in providing therapy treatment for patients managed with this relatively new synthetic dermal substitute. Trends indicated that as experience with this new dermal substitute grew, patients progressed toward active therapy earlier. A guideline for therapy treatment has been developed but will continue to be evaluated and adjusted when required., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

The reconstructed skin micronucleus (RSMN) assay was developed in 2006, as an in vitro alternative for genotoxicity evaluation of dermally applied chemicals or products. In the years since, significant progress has been made in the optimization of the assay, including publication of a standard protocol and extensive validation. However, the diverse morphology of skin cells makes cell preparation and scoring of micronuclei (MN) tedious and subjective, thus requiring a high level of technical expertise for evaluation. This ultimately has a negative impact on throughput and the assay would benefit by the development of an automated method which could reduce scoring subjectivity while also improving the robustness of the assay by increasing the number of cells that can be scored. Imaging flow cytometry (IFC) with the ImageStream ®X Mk II can capture high-resolution transmission and fluorescent imagery of cells in suspension. This proof-of-principle study describes protocol modifications that enable such automated measurement in 3D skin cells following exposure to mitomycin C and colchicine. IFC was then used for automated image capture and the Amnis® Artificial Intelligence (AAI) software permitted identification of binucleated (BN) cells with 91% precision. On average, three times as many BN cells from control samples were evaluated using IFC compared to the standard manual analysis. When IFC MNBN cells were visually scored from within the BN cell images, their frequency compared well with manual slide scoring, showing that IFC technology can be applied to the RSMN assay. This method enables faster time to result than microscope-based scoring and the initial studies presented here demonstrate its capability for the detection of statistically significant increases in MNBN frequencies. This work therefore demonstrates the feasibility of combining IFC and AAI to automate scoring for the RSMN assay and to improve its throughput and statistical robustness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Artificial dermal skin substitutes (ADSS) in combination with split-thickness skin grafts (STSG) are a valuable option for reconstruction of skin- and soft tissue-defects. However, successful incorporation of ADSS can be limited by various factors. We investigated the anticipated benefits of negative pressure wound therapy (NPWT) as an adjunct to support integration of ADSS, in a retrospective, comparative cohort study., Patients and Methods: We performed a retrospective, non-blinded, non-randomized comparative study including 86 patients with various soft-tissue defects, managed by application of either ADSS with or without NPWT based on the surgeon's preference. Outcome measurements comprised ADSS and skin graft take rates and analysis of treatment duration and time to wound healing. Additionally, patients were analyzed for the occurrence of hematoma, seroma, wound infection, and lack of substitute or skin graft adhesion., Results: Demographic data and individual risk factors did not differ with statistical significance between both groups. The combination of ADSS with NPWT led to significantly improved rates of ADSS integration (89 vs. 70.1%; p = 0.035) and skin graft take (91 vs. 76%; p = 0.049) compared to standard wound dressings without NPWT. In addition, while differences in the incidence of seroma were neglectable, NPWT application led to significantly reduced rates of infection of ADSS (2.2 vs. 7.3%; p = 0.043). Moreover, STSG could be performed on average 4 days earlier with the application of NPWT (p = 0.031)., Conclusions: The addition of NPWT to ADSS is a helpful adjunct that reduces time of incorporation and vascularization and improves clinical success rates., Competing Interests: Conflict of interest statement CH has consulted for Integra Lifesciences, Saint Priest, France, and KCI – 3 M, Wiesbaden, Germany. SF and DK received funding from Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany, for an independent research project. For the remaining authors, none were declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The inability of two-dimensional cell culture systems to adequately map the structure and function of complex organs like skin necessitates the development of three-dimensional (3D) skin models. A diverse range of 3D skin equivalents have been developed over the last few decades for studying complex properties of skin as well as for drug discovery and clinical applications for skin regeneration in chronic wounds, such as diabetic foot ulcers, where the normal mechanism of wound healing is compromised. These 3D skin substitutes also serve as a suitable alternative to animal models in industrial applications and fundamental research. With the emergence of tissue engineering, new scaffolds and matrices have been integrated into 3D cell culture systems, along with gene therapy approaches, to increase the efficacy of transplanted cells in skin regeneration. This review summarizes recent approaches to the development of skin equivalents as well as different models for studying skin diseases and properties and current therapeutic applications of skin substitutes., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The aim of this work was to develop new method for the production of chitosan/agarose (CHN/A) film that could serve as a potential artificial skin substitute for regenerative medicine applications. Within this new production method, the concentrations of biomaterial components (chitosan in CH 3 COOH and agarose in NaOH) were optimized to provide neutralization of the resultant mixture up to pH approx. 6.0 without uncontrolled precipitation (gelation) of chitosan constituent. Produced thin film was subjected to comprehensive evaluation of its biomedical potential by determination of mechanical, physicochemical, and biological properties. It was demonstrated that the developed CHN/A film reveals slightly acidic pH of 5.98 known to support skin regeneration, high exudate absorption capacity, and is prone to biodegradation in simulated enzymatic wound environment. Performed tensile test proved high elastic deformations of the film (Young's modulus = 0.02 MPa, elongation at break = 23%) in a wet state, which would allow suitable stretching after application at the wound site. Moreover, novel biomaterial is non-toxic and supports fibroblast growth on its surface. Based on the obtained results it may be concluded that the produced CHN/A film possesses all necessary features of the artificial skin substitute., 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 © 2020 Elsevier B.V. All rights reserved.)

Pelnac Gplus Ⓡ , Integra Ⓡ , and Terudermis Ⓡ are approved artificial dermis products in Japan. Previously, we proved that Pelnac Gplus Ⓡ was able to sustain basic fibroblast growth factor (bFGF) and accelerated wound healing by releasing impregnated bFGF. In this study, we impregnated Pelnac Gplus Ⓡ , Integra Ⓡ , and Terudermis Ⓡ with bFGF and compared the binding activity and wound-healing process. We applied bFGF to each material and compared the bFGF concentrations in the surrounding area after 24-h incubation. For the in vivo study, dermal substitutes were impregnated with bFGF and implanted into full-thickness wounds of BKS.Cg-+Leprdb/+Leprdb/Jcl mice. Wounds were evaluated at days 7, 14, and 21 after implantation. The in vitro study showed that bFGF is strongly bound to Integra Ⓡ , followed by Pelnac Gplus Ⓡ and Terudermis Ⓡ . The in vivo study showed that fibroblasts and capillaries had infiltrated into the Pelnac Gplus Ⓡ but not the Integra Ⓡ or Terudermis Ⓡ . Furthermore, long epithelium and wide granulation tissue were formed in the Pelnac Gplus Ⓡ with bFGF group. The Terudermis Ⓡ with bFGF group had more capillaries than other groups, but only at the base of the wound. The combination of Pelnac Gplus Ⓡ with bFGF may be a novel approach for treating full-thickness skin defects or chronic skin ulcers., Competing Interests: Conflict of interest This research was supported partially by the research promotion grant of Kansai Medical University and partially funded by grants for research received from Gunze Ltd. The funder had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aplasia cutis congenita is defined as the absence of all layers of the skin. The condition involves mainly the scalp but it can affect any area of skin on the body. A clear therapeutic strategy is not available. Here, we describe the 6-year clinical outcome of a patient with aplasia cutis congenita of both knees following treatment with an artificial dermis and a thin skin graft., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Biodegradable polyesters have been widely used as rigid biomedical apparatus because of high mechanical properties but few flexible implants. Herein, we report a flexible poly(lactide-co-glycolide) (PLGA) scaffold using a rapid in situ formation system based on phase separation by solvent exchange deposition modeling (SEDM), which was different from traditional 3D printing of fused deposition modeling (FDM). The FDM printed product was rigidity, its Young's modulus was approximate 2.6 times higher than that of SEDM printed sample. In addition, the thickness of the solidified ink would not shrink during the SEDM printing process, its surface had nano-/micro pores in favor of protein immobilization and cell adhesion. Then a flexible bilayered scaffold with nano-/microstructure was constructed combing SEDM with electrospinning technology for skin substitute, wherein the SEDM printed sample acted as a sub-layer for cell and tissue ingrowth, the densely packed electrospun nanofibers served as an upper-layer improving the sub-layer's tensile strength by 57.07% and preventing from bacteria as physical barrier. Ultimately, the bilayered scaffold immobilized epidermal growth factor (EGF) by a bioorthogonal approach was successfully applied to facilitate full-thickness wound healing of rats., 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 © 2020. Published by Elsevier B.V.)

Purpose: After harvesting a radial forearm flap (RFF) an optimal aesthetic and functional restitution of the donor site is required. In order to cover the secondary defect of the donor site, several solutions are currently available, but there is still no real evidence of the most reliable option. A retrospective study was conducted in order to evaluate a new technique of forearm coverage with artificial dermis: the association of full thickness skin graft (FTSG) with Matriderm®., Methods: Our study included all RFF performed during a 34-month period. Forty-three forearm secondary defects after harvesting a RFF (16 men, 27 female) were included. Forearm donor site was covered using three techniques: a simple FTSG, split thickness skin graft (STSG) with Matriderm® or FTSG with Matriderm®. Clinical evaluations based on residual functionality, skin quality and aesthetic result were assessed using respectively the Disabilities of the Arm, Shoulder and Hand (DASH) score, the Vancouver Scar Scale (VSS) score and a blind panel questionnaire., Results: FTSG with Matriderm® showed an improved DASH (10.6/100) and VSS score (5.5/13) if compared to the other techniques, mean surgeon satisfaction score was 3/5, mean patient satisfaction score was 3/5 in the FTSG with Matriderm® group., Conclusion: The results of this study revealed that the new association of FTSG with Matriderm® improves the DASH score and the aesthetic outcomes resulting to be a reliable solution in treating full thickness forearm skin defects after RFF harvesting., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: In a previous study, our group demonstrated that cultured autologous fibroblast-seeded artificial dermis was superior to artificial dermis for covering defects after surgical excision of basal cell carcinoma (BCC) in terms of scar quality. However, utilizing cultured cells for clinical purposes requires Food and Drug Administration-approved facilities and techniques and a lengthy culture period. The purpose of this retrospective study was to compare the effects of tissue-engineered dermis containing stromal vascular fraction (SVF) cells with artificial dermis on scar quality after surgical excision of BCC on the nose., Methods: Between April 2010 and February 2018, patients who were treated with tissue-engineered or artificial dermis grafts and those with a follow-up period of greater than a year were included in this study. The Patient and Observer Scar Assessment Scales (POSAS) were compared between two groups according to the location of the graft, which was classified based on nasal subunits: the upper two-thirds zone; the lower one-third zone, except for the ala; and the alar zone., Results: A tissue-engineered dermis composed of SVF cells and an artificial dermis were applied to 30 and 47 patients, respectively. In upper two-thirds and lower one-third zones, except for the ala, no statistically significant differences were found in any parameters. In the alar zone, statistically significant differences were detected in 10 of 21 POSAS parameters., Conclusion: To cover nasal defects, the tissue-engineered dermis graft may be superior to the artificial dermis graft regarding scar quality at the ala. However, there were no significant differences in other zones., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to disclose., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: Thermal burns are the most common type of skin injuries. Clinically, the deteriorating thermal wounds have been successfully treated with skin cell sheets, suspensions or bioengineered skin substitutes. After thermal injury, oxidative microenvironment prevalent in the burnt tissue due to imbalance between production of free radicals and antioxidants defense aiding to destruction of cellular or tissue components. However, depleted antioxidant content particularly vitamin E after heat injury challenges efficient regenerative and healing capacity of transplanted cells. Thus, aim of current study was to pretreat human epidermal keratinocytes with vitamin E in order to enhance their survival rate and therapeutic ability under oxidative microenvironment induced by in vitro heat stress., Main Methods: Keratinocytes were treated with 100 μM vitamin E at 37 °C for 24 h followed by thermal stress at 51 °C for 10 min. Cell viability and cytotoxicity assays, gene expression analysis and paracrine release analysis were performed., Key Findings: Vitamin E preconditioning resulted in significantly improved cell morphology, enhanced viability and reduced lactate dehydrogenase release. Furthermore, Vitamin E preconditioned cells exposed to thermal stress showed significant down-regulated expression of BAX and up-regulated expression of PCNA, BCL-XL, vascular endothelial growth factor (VEGF), involucrin, transglutaminase 1 (TGM1) and filaggrin (FLG) escorted by increased paracrine release of VEGF, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)., Significance: Results of the current study suggest that clinical transplantation of vitamin E preconditioned keratinocytes alone or in combination with dermal fibroblasts in skin substitutes for the treatment of thermally injured skin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Urethrocutaneous fistula UCF is the most common complication following surgical repair of hypospadias. Currently, the surgical technique mostly used to prevent recurrence employs preputial dartos or testicular tunica vaginalis flaps as a urethral covering. However, autologous tissues are limited in patients with multiple surgeries, and the use of biomaterials as a urethral coverage may represent a good alternative., Objective: The goal of the present study is to assess the results and complications of recurrent UCF correction using a dermal bovine regeneration sheet as a urethral covering., Materials and Method: From May 2016 to January 2019, all patients with recurrent UCF of the authors center were repaired using this technique. The inclusion criteria were patients who had undergone one or more unsuccessful UCF repair surgeries and the absence of preputial tissue. The informed consent has been signed by all the patients. Patients were examined in outpatient consultations where their urinary stream was evaluated and a physical examination of the penis was conducted., Results: A total of 12 patients and 13 UCFs were included in the study. The median follow-up was 18 months, (range: 4-26), and only two patients (15%) developed a recurrence of UCF. No complications were observed in the remaining patients (85%) during their evolution. No patient developed a fibrosis increase or loss of elasticity of the tissues in contact with the dermal matrix., Conclusion: The use of an Integra® sheet as a urethral covering during urethral fistula surgery appears to be a safe, effective, and easily reproducible option. However, prospective studies with larger numbers of patients should be performed to corroborate these results., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Skin substitutes for deep wound healing require meticulous designing and fabrication to ensure proper structural and functional regeneration of the tissue. Range of physical and mechanical properties conducive for regeneration of different layers of skin is a prerequisite of an ideal scaffold. However, single or bilayer substitutes, lacking this feature, fail to heal full thickness wound. Complete scar free regeneration of skin is still a big challenge. This study reports fabrication of a trilayer scaffold, from biodegradable polymers that can provide the right ambience for simultaneous regeneration of all the three layers of skin. The scaffold was developed through optimization of different fabrication techniques, namely, casting, electrospinning and lyophilisation, for obtaining a tailored trilayer structure. It has mechanical strength similar to skin layers, can maintain a porosity-gradient and provides microenvironments suitable for simultaneous regeneration of epidermis, dermis and hypodermis. A co-culture model, of keratinocytes and dermal fibroblasts, confirms the efficiency of the scaffold in supporting proliferation and differentiation of different types of cells, into organized tissue. The scaffold showed improved and expedited wound healing in-vivo. Taken together, these compelling evidences successfully established the engineered trilayer scaffold as a promising template for skin tissue regeneration in case of deep wound., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Animal studies indicate treating burn injuries with running water (first aid) for 20 min up to 3 h after burn reduces healing time and scarring. We have previously demonstrated the benefits of first aid in minor burn injuries with respect to a reduction in wound depth, faster healing, and decreased skin grafting utilisation. The purpose of this cohort study was to assess the effect of first aid on clinical outcomes in large body surface area burn injuries (≥20%)., Methods: Data was prospectively collected for patients with ≥20% TBSA burns from 2004- 2018. Multivariate regression analysis was used to determine the association of adequate first aid with 8 outcomes - mortality, total length of stay, total body surface area (TBSA), percentage/proportion of TBSA that was full thickness [PFTI], TBSA grafted, number of re-grafting sessions, intensive care admission, and intensive care length of stay. Adequate first aid was defined as the application of 20 min of cool, running tap water up to 3 h following the burn injury., Findings: 390 patients were identified. Adequate first aid was received in 35.6% (139) of patients. There was a trend towards a reduction in mortality (OR 0.37; 95% CI 0.12-1.13; P = 0.08). Patients who received adequate first aid had a statistically significant 9.8% reduction in TBSA (95% CI -13.6% to -6.1%; P < 0.0001) as well as a 12% lower PTFI compared to patients who received inadequate first aid (95% CI -19% to -4%; P < 0.01). Whilst there was no significant effect of adequate first aid on the TBSA grafted (P = 0.37), adequate first aid was associated with a significantly less number of re-grafting sessions (95% CI --0.29 to -0.08; P < 0.001)., Interpretation: Adequate first aid with 20 min of running water is associated with improved outcomes in large burn injuries. Significant benefits are seen in a reduction in TBSA, proportion of the burn wound that is full thickness, as well as decreased re-grafting. This has significant patient and health system benefits and adds to the body of evidence supporting 20 min of cooling in burns care., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Objective: This open-label, controlled, randomized study assessed the safety, tolerability, and efficacy of StrataGraft tissue compared to autograft in the treatment of deep partial-thickness (DPT) burns., Methods: Thirty subjects with DPT thermal burns (3%-43% total body surface area) were treated with StrataGraft tissue as follows: cohort 1, ≤220 cm 2 refrigerated tissue; cohort 2, ≤440 cm 2 refrigerated tissue; and cohort 3, ≤440 cm 2 cryopreserved tissue. On each subject, two comparable areas of DPT burn were randomized to receive StrataGraft tissue or autograft. Coprimary end points were the percent area of the StrataGraft tissue treatment site undergoing salvage autografting by Day 28 and wound closure of treatment sites by 3 months., Results: By Day 28, no StrataGraft tissue treatment sites underwent autografting. By 3 months, 93% and 100% of the StrataGraft tissue and autograft treatment sites achieved complete wound closure, respectively. No significant differences in observer total and overall opinion POSAS scores between StrataGraft tissue and autograft treatment sites were observed at any timepoint. The most common adverse event was pruritus (17%)., Conclusions: StrataGraft tissue treatment of DPT thermal burns reduced the need for autograft, resulted in wound closure and treatment-site cosmesis comparable to that of autograft, and was well tolerated., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dermal exposure to metals has previously received less attention than oral/inhalation exposure. Nonetheless, human health risk is significant for certain contaminants and exposure scenarios. The present study aims to (1) characterize two certified reference soils (SQC001, BGS 102); and (2) assess Cr, Ni, Pb, and Zn dermal bioaccessibility via in vitro assays using three synthetic sweat formulations (EN 1811, pH 6.5 (Sweat A), NIHS 96-10, pH 4.7 (Sweat B), and a more complex pH 5.5 formulation containing amino acids (Sweat C)) and two sebum formulations. Metals bioaccessibility in sweat followed Sweat B > Sweat C > Sweat A, attributed to sweat B lower pH. Dermal bioaccessibility in both sebum formulations was lower than 1% for Ni and Pb and below 9% for Cr and Zn, possibly due to low affinity of metals for non-polar lipids. It must be noted that bioaccessible Zn in BGS 102 was higher when extracted with synthetic sebum compared to any of the synthetic sweat formulations. Metal bioaccessibility in sweat was considerably higher for SQC001 (up to 76.6% for Zn using Sweat B) than for BGS 102 (ranging between 0.02 and 1.3% for all elements and all sweat formulations), attributed to higher pH, higher organic carbon, and higher cation exchange capacity of reference soil BGS 102. Sebum formulations spiked with metals generally entailed low metal recovery (except for Zn), which may explain overall low bioaccessibility values for sebum. Sebum and sweat formulation, and soil properties seem to control in vitro dermal bioaccessibility of metals., (Copyright © 2019. Published by Elsevier B.V.)

The gold standard treatment for severe burn injuries is autologous skin grafting and the use of commercial dermal substitutes. However, resulting skin tissue following treatment usually displays abnormal morphology and functionality including scarring, skin contracture due to the poor elasticity and strength of existing dermal substitutes. In this study, we have developed a triple-polymer scaffold made of collagen-elastin-polycaprolactone (CEP) composite, aiming to enhance the mechanical properties of the scaffold while retaining its biological properties in promoting cell attachment, proliferation and tissue regeneration. The inclusion of elastin was revealed to decrease the stiffness of the scaffold, while also decreasing hysteresis and increasing elasticity. In mice, electrospun collagen-elastin-PCL scaffolds promoted keratinocyte and fibroblast proliferation, tissue integration and accelerated early-stage angiogenesis. Only a mild inflammatory response was observed in the first 2 weeks post-subcutaneous implantation. Our data indicates that the electrospun collagen-elastin-PCL scaffolds could potentially serve as a skin substitute to promote skin cell growth and tissue regeneration after severe burn injury., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)