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Using a flap in a large wound with a very small area of exposed vital structures may be an excessive intrusion and cause unnecessary donor site morbidity. Dermal matrix (DuraGen) was applied onto critical areas where bone or tendons were exposed and a split skin graft was placed thereon. All patients had satisfactory wound closure without the need for a flap. DuraGen appears to be a safe, single-stage alternative, to a flap for the healing of complex wounds., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

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.)

Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos' dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos' dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals., (© 2024. The Author(s).)

Reconstitution of normal skin anatomy after full-thickness skin loss may be accomplished using a combination of a dermal regeneration template (DRT) and a split thickness skin graft (STSG). However, because of the relatively low rate of cell infiltration and vascularisation of currently available DRTs, reconstruction is almost always performed in a two-step procedure over the course of several weeks, resulting in multiple dressing changes, prolonged immobilisation and increased chance of infection. To mitigate the potential complications of this prolonged process, the collagen-based dermal template DermiSphere™ was developed and tested in a single-step procedure wherein DermiSphere and STSG were implanted simultaneously. When evaluated in a porcine, full thickness, excisional wound model, DermiSphere successfully supported simultaneous split thickness skin graft take and induced functional neodermal tissue deposition. When compared to a market leading product Integra Bilayer Wound Matrix, which was used in a multistep procedure (STSG placed 14 days after product implantation according to the product IFU), DermiSphere induced a similar moderate and transient inflammatory response that produced similar neodermal tissue maturity, thickness and vascularity, despite being implanted in a single surgical procedure leading to wound closure 2 weeks earlier. These data suggest that DermiSphere may be implanted in a single-step procedure with an STSG, which would significantly shorten the time course required for the reconstruction of both dermal and epidermal components of skin after full thickness loss., (© 2023 The Wound Healing Society.)

Wound healing of skin defects is complex. For the treatment of large and deep wounds, it is a good alternative to accept artificial dermis grafting at the first stage surgery, and autologous split-thickness skin grafting 2-3 weeks later at the second stage surgery. In addition, the effectiveness of numerous cytokines such as fibroblast growth factor (FGF) on wounds healing has been widely researched. The traditional view is that direct external application or in vivo injection of exogenous FGFs may not achieve the desired therapeutic effect as the effective concentration cannot be maintained for a long time. Therefore, some researchers have tried to integrate various cytokines into skin substitutes for combined application. However, we believe that considering the current situation, it is still difficult to achieve mass production of these types of artificial dermis. Here, we manufactured a collagen-chondroitin sulfate scaffold material by imitating the marketed artificial dermis materials. Then, we combined it with recombinant human acidic FGF in a single full dose during the first-stage artificial dermis transplantation, which is simple and completely feasible but always controversial in the current clinical work, to explore whether this combinatorial therapy could serve as an efficient way wound healing in the Balb/c-nu mice full-thickness skin defect model., (© 2022 IOP Publishing Ltd.)

Skin is a multilayer organ consisting of several tissues and appendages residing in a complex niche. Adequate and physiologically regulated vascularization is an absolute requirement for skin homeostasis, regeneration, and wound healing. The lack of vascular networks and ischemia results in delayed wound closure. In addition, vascularization is critical for the prolonged function and survival of skin grafts and tissue-engineered skin substitutes. This study highlights the clinical challenges associated with the limited vascularization in the cutaneous wounds. Then, we highlight the novel approaches for the development of vascular networks in the skin autografts, allografts, and artificial substitutes. Also, the future directions to overcome the existing vascularization complications in skin grafting and synthetic skin substitutes are presented. Statement of Significance Delayed closure of large dermal wounds, such as burn injuries, results from the lack of vascular networks and ischemia. The amount of blood supply in the skin graft is the primary factor determining the quality of the transplanted grafts. The current skin grafts and their fabrication methods lack the appropriate features that contribute to the vascularization and integration of the wound bed and graft and adherence to the skin layers. Therefore, the new generation of skin grafts should consider advanced technologies to induce vascularization and overcome current challenges.

CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26 + or CD26 knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26 + fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation., (© 2022. The Author(s).)

Optimal treatment of full-thickness skin injuries requires dermal and epidermal replacement. To spare donor dermis, dermal substitutes can be used ahead of split-thickness skin graft (STSG) application. However, this two-stage procedure requires an additional general anaesthetic, often prolongs hospitalisation, and increases outpatient services. Although a few case series have described successful single-stage reconstructions, with application of both STSG and dermal substitute at the index operation, we have little understanding of how the physical characteristics of dermal substitutes affects the success of a single-stage procedure. Here, we evaluated several dermal substitutes to optimise single-stage skin replacement in a preclinical porcine model. A porcine full-thickness excisional wound model was used to evaluate the following dermal substitutes: autologous dermal graft (ADG; thicknesses 0.15-0.60 mm), Integra (0.4-0.8 mm), Alloderm (0.9-1.6 mm), and chitosan-based hydrogel (0.1-0.2 mm). After excision, each wound was treated with either a dermal substitute followed by STSG or STSG alone (control). Endpoints included graft take at postoperative days (PODs) 7 and 14, wound closure at POD 28, and wound contracture from POD 28-120. Graft take was highest in the STSG alone and hydrogel groups at POD 14 (86.9% ± 19.5% and 81.3% ± 12.3%, respectively; P < .001). There were no differences in graft take at POD 7 or in wound closure at POD 28, though highest rates of wound closure were seen in the STSG alone and hydrogel groups (93.6% ± 9.1% and 99.8% ± 0.5%, respectively). ADG-treated wounds demonstrated the least amount of wound contracture at each time point. Increase dermal substitute thickness was associated with worse percent graft take at PODs 14 and 28 (Spearman ρ of -0.50 and -0.45, respectively; P < .001). In this preclinical single-stage skin reconstruction model, thinner ADG and hydrogel dermal substitutes outperformed thicker dermal substitutes. Both substitute thickness and composition affect treatment success. Further preclinical and clinical studies to optimise this treatment modality are warranted., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Management of post-operative soft-tissue defects on the lower legs is challenging owing to arterial and venous insufficiency, poor skin quality including epidermal and dermal atrophy, insufficient tissue laxity, and increased risk of infection. This paper highlights the management of post-operative soft-tissue defects on the lower extremity that cannot be closed primarily or by reconstruction with a local flap. A systematic review of the literature was performed using the National Library of Medicine (NLM) PubMed online database. Articles were included if they reported the management of post-operative lower extremity soft-tissue defects with secondary intention healing, full-thickness skin graft, split-thickness skin grafts, or skin substitutes. Sixty-three articles were included for analysis. There are several options for managing surgical defects on the lower legs and the method chosen should depend on various factors, including the quality of the skin, vascularity and size of the defect, medical history of the patient, and the experience of the surgeon.

Introduction: In large full-thickness skin defects, donor site morbidity limits the available thickness and surface of skin autografts and therefore only split-thickness skin grafts are possible for reconstruction. Dermal equivalents can be added to these split-thickness grafts to acquire an anatomically better skin reconstruction. Glyaderm is a human derived, acellular dermis and up until now has only been used in a two-staged procedure. This report describes results of a case series using Glyaderm and split-thickness skin grafts in a single-staged procedure., Methods: Glyaderm was introduced in 2017 in Radboudumc (Nijmegen, The Netherlands). Glyaderm and autologous split-skin grafts were simultaneously applied to the wounds. In cases with large wound surfaces or wounds covering highly mobile areas, negative pressure wound therapy was additionally applied. The first ten cases were followed with regular intervals post-operatively, assessing graft take, scar appearance, post-operative wound problems and re-interventions., Results: Patients were aged 3 weeks to 76 years-old. Treated skin surface varied from 1-16% total body surface. Wounds resulted from trauma (n = 4), burns (n = 4) or soft tissue infections (n = 2). Follow-up varied from 4 months to 1.5 years. No complications occurred after surgery. Average take rate was 98%. Two patients had a later re-intervention to further improve the aesthetic appearance of the scarred area., Conclusion: Our first results with the application of Glyaderm in a single-staged procedure provided good healing, graft take and scar appearance. Glyaderm was found a suitable dermal substitute in the treatment of full thickness wounds.

Given that many people suffer from extensive skin damage, wound repair has drawn tremendous attention in research. Among the various assistant dressing materials that promote healing, a porcine acellular dermal matrix (PADM), as a skin substitute, can efficiently accelerate healing by promoting cell migration and proliferation. However, a simple, low-cost preparation process remains a challenge facing PADM development, particularly because of the inferior elasticity. To overcome these drawbacks, a CaCl 2 -ethanol-H 2 O solution (ternary solution) combined with an additional enzyme treatment was used to obtain a transparent, porous, and elastic PADM that retained the major extracellular matrix composition of the dermis. Our results indicated that alterations in the fiber organization and secondary structural changes in the collagen occurred after treatment. Furthermore, the in vivo wound healing and histological analyses clearly revealed an extremely expedited wound repair process following the application of the biocompatible PADM. In conclusion, this study provides new insights into the development of a transparent PADM with a porous structure and good elasticity that can be used as a skin substitute to accelerate the wound healing process. Moreover, this effective technique could potentially be used to extrapolate other decellularized materials in the future.

Objective: Full-thickness burn wounds require immediate coverage, and the primary clinical approaches comprise of skin allografts and autografts. The use of allografts is often temporary due to the antigenicity of allografts. In contrast, the availability of skin autografts may be limited in large burn injuries. In such cases, skin autografts can be expanded through the use of a skin mesher, creating meshed split-thickness skin grafts (MSTSGs). MSTSGs have revolutionized the treatment of large full-thickness burn injuries since the 1960s. However, contractures and poor esthetic outcomes remain a problem. We previously formulated and prepared an in situ forming skin substitute, called MeshFill (MF), which can conform to complex shapes and contours of wounds. The objective of this study was to assess the esthetic and wound healing outcomes in full-thickness wounds treated with a combination of MF and MSTSG in a porcine model. Approach: Either MSTSGs or MSTSG+MF was applied to full-thickness excisional wounds in Yorkshire pigs. Wound healing outcomes were assessed using histology, immunohistochemistry, and wound surface area analysis from day 10 to 60. Clinical evaluation of wounds were utilized to assess esthetic outcomes. Results: The results demonstrated that the combination of MSTSGs and MF improved wound healing and esthetic outcomes. Innovation: Effects of MSTSGs and reconstitutable liquid MF in a full-thickness porcine model were investigated for the first time. Conclusion: MF provides promise as a combination therapeutic regimen to improve wound healing and esthetic outcomes.

Severe skin burns are widely treated using split-thickness skin autografts. However, the accessibility of the donor site may be limited depending on the size of the injured surface. As an alternative to skin autografts, our laboratory is clinically investigating a model of human self-assembled skin substitute (SASS) with a standard size of 35 cm 2 . For the management of extensive skin wounds, multiple grafts are required to cover the entire wound bed. Even if SASSs could provide an adequate and efficient treatment, in some cases, the long-term follow-up of the skin graft site reveals the appearance of marks at the junction between SASSs. This study aims to produce a large-sized self-assembled skin substitute (L-SASS; 289 cm 2 ) and evaluate its preclinical potential for skin wound coverage. The L-SASSs and SASSs shared similar contraction behavior on an agar surface, thickness, and epidermal differentiation in vitro. After grafting, similar histological results were obtained for skin substitutes produced with both methods. Hence, the self-assembly approach of tissue engineering is a scaffold-free method that allows the production of living skin substitutes in a large format.

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 purpose of this study was to evaluate the therapeutic effects of artificial dermis combined with autologous split-thickness skin grafting (STSG) compared with autologous intermediate-thickness skin grafting (ITSG) alone in severely burned patients. Fifty-six severely burned patients admitted to our hospital from December 2017 to January 2019 were enrolled and evenly grouped according to the random number table method [AD-STSG group: 28 patients, receiving the treatment of artificial dermis (AD) combined with autologous STSG; ITSG group: 28 patients, receiving autologous ITSG treatment alone]. The healing time and Vancouver Scar Scale (VSS) score of the donor area and graft area, survival rate and infection status of the autologous skin, psychological status (determined by Self-rating Anxiety Scale and Self-rating Depression Scale), and the activity of functional parts of all enrolled patients were included in the evaluation. General items of patients in AD-STSG group and ITSG group, including age, sex, and degree of burn, were all comparable. A significantly shortened healing time of donor skin in AD-STSG group was observed when compared with ITSG group (P < .05) while the recipient skin healed in the same tendency between the two groups. In addition, 21 days after the operation, AD-STSG group presented with significantly higher survival rate of graft skin than ITSG group (P < .05) while same infection status was observed in the two groups. Significantly lower VSS scores were found in AD-STSG group than that in ITSG group 3-, 6- and 10-months after operation (P < .05). Statistical difference regarding psychological status of patients from two groups was unobservable before operation while significantly lower Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were found in AD-STSG group than that in ITSG group 3-, 6- and 10-months after operation (P < .05). Also, AD-STSG group presented improved mobility of functional part than that in ITSG group 10-months after operation without statistical difference (P = .051). Artificial dermis combined with autologous split-thickness skin grafting showed better therapeutic outcomes for the treatment of severely burned patients than autologous intermediate-thickness skin grafting in terms of graft healing time, scar formation, psychological recovery, and perhaps in functional reconstruction., (© 2020 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation., (© 2021 S. Karger AG, Basel.)

Objective: Soft tissue defects, especially those involving exposed vital structures, present a reconstructive challenge because poor vascularity of such defects typically makes immediate skin grafting unviable. Where flap procedures are inappropriate or not possible, dermal matrices represent an alternative reconstructive option for defects with denuded vital structures. With dermal matrices becoming increasingly available and technologically advanced, we evaluated an ovine-derived extracellular matrix graft in the reconstruction of complex soft tissue defects involving exposed vital structures., Method: Six cases of soft tissue defects exhibiting denuded vital structures underwent reconstruction using an ovine forestomach matrix graft as a dermal matrix. Grafts were fixed directly into defects for immediate coverage and subsequently temporised defects via granulation tissue formation for later skin graft or secondary closure. Defect granulation and epithelialisation were monitored until closure and the final aesthetic and functional outcomes were evaluated., Results: Complete healing was achieved in all cases, with defect granulation becoming observable within one to two weeks and complete granulation occurring within one to six weeks. Granulation tissue resulting from the graft was suitable for skin grafting, with 100% take of skin grafts after one week and complete re-epithelialisation in two to three weeks in the four cases that received a skin graft. Good cosmetic, functional and patient satisfaction outcomes were achieved in all cases., Conclusion: The present series demonstrates our initial use of an extracellular matrix-based dermal matrix in reconstructing defects with exposed vital structures. While such dermal matrices do not supersede or replace flap procedures, they represent an alternative option on the reconstructive ladder in cases where flap procedures are not appropriate or possible.

Background: Tissue engineering is used to fabricate 3-dimensional (3D) artificial scaffolds to create a microenvironment that mimics human tissue. Bioprinting uses biomaterials, cells, and/or bioink to fabricate prospective scaffolds to mirror the structural, compositional, and functional aspects of the skin. Various bioprinting methods (inkjet-based bioprinting, pressure-assisted bioprinting, and laser-assisted bioprinting) have been used for regenerative wound repair and have been characterized based on biocompatibility, cellular microenvironment, cell proliferation, vitality, and morphology., Objective: This article reviews the basic principles of 3D printing, current 3D skin bioprinting applications and approaches, and future directions for regenerative medical skin constructs., Methods: A comprehensive literature review was conducted using PubMed with keywords "three-dimensional printing," "dermatologic surgery," "bioprinting," "reconstructive surgical procedures," "wound healing," "skin grafts," "skin scaffolds," "tissue reconstruction," and "tissue engineering.", Results: A summary of the different applications and 3-dimensional skin bioprinting techniques is presented. In addition, synthetic, natural, and combination polymers are reviewed. Advantages, disadvantages, indications, and approaches are discussed in depth., Conclusion: Skin grafting is a dynamic technique of dermal reconstruction that can be successful with comprehensive knowledge of skin bioprinting methods.

Background: Management of skin and soft-tissue defects of the fingertips is functionally and aesthetically important, but controversial, especially when bones are exposed. Recent advances in wound healing technology allow the use of cells or biological dermis. The authors studied the clinical efficacy of tissue-engineered dermis grafts and artificial dermis grafts versus immediate reconstructive procedures, such as the reverse digital artery island flap, in treating bone-exposed fingertip defects., Methods: One hundred eighty-two patients with bone-exposed fingertip defects treated with tissue-engineered dermis grafts (n = 71), artificial dermis grafts (n = 23), or reverse digital artery island flaps (n = 88) were included in this retrospective cohort study. Surgical time, duration of hospitalization, total cost, success rate, healing time, sensory recovery, range of motion, scar quality, and patient satisfaction were compared., Results: No tissue-engineered or artificial dermis graft exhibited graft rejection or failure, whereas there was one partial loss and one total loss after reverse digital artery island flap surgery. Tissue-engineered dermis grafts were superior in scar quality, and artificial dermis grafts had shorter surgical times and lower surgical costs; both groups demonstrated superior results in postoperative range of motion and sensory recovery in two-point discrimination tests and shorter hospitalization, compared with the reverse digital artery island flap group. The reverse digital artery island flap had shorter complete closure time and less postoperative tingling sensation. There were no differences in overall patient satisfaction among the groups., Conclusions: Tissue-engineered and artificial dermis grafts may be promising alternatives for fingertip reconstruction. In particular, tissue-engineered dermis grafts may deliver superior functional results, including recovery of sensory discomfort and aesthetic results in terms of scar quality over artificial dermis grafts., Clinical Question/level of Evidence: Therapeutic, III.

To date, skin substitute that can provide permanent wound closure is still autologous tissue-engineered skin using autologous skin cells as seed cells. The development of cultured epithelial autograft has experienced a long and tortuous process. Autologous tissue-engineered composite skin is closer to autologous split-thickness skin graft in terms of structure, function, and efficacy, which has become a research focus in recent years. Based on the actual status of research on tissue-engineered skin application, this paper reviewed the main research progresses and existing problems, and the prospect of research and development and clinical application of autologous tissue-engineered skin as permanent graft in order to provide a reference for the improvement and application of autologous tissue-engineered skin.

Introduction: Acellular dermal matrix (ADM) products are adopted in the management of injuries to soft tissues. ADMs have been increasingly employed for their clinical advantages, and they are acquiring relevance in the future of plastic surgery. The aim of our study is to evaluate the application of ADMs in our patients who could not undergo fast reconstruction., Materials and Methods: We performed a retrospective study on 12 patients who underwent ADM placement for scalp and limb surgical reconstructions at the Humanitas Research Hospital, Rozzano (Milano), Italy. Wounds resulted from 9 tumor resections and 3 chronic ulcers. The ADM substrate used to treat these lesions was PELNAC™ (Gunze, Japan), a double-layered matrix composed of atelocollagen porcine tendon and silicon reinforcement. All patients underwent a second surgical operation to complete the treatment with a full-thickness skin graft to cover the lesion., Results: In this study, 12 patients were treated with PELNAC™: 11 out of 12 patients showed a good attachment over a median time of 21.3 days (range 14-27). After almost 23 days, all patients were ready to undergo a full-thickness skin grafting., Conclusion: This study assesses the benefits of PELNAC™ and proposes this method as an alternative to traditional approaches, especially in situations where the latter techniques cannot be applied., Competing Interests: No conflict of interest exists between the authors., (Copyright © 2020 Andrea Vittorio Emanuele Lisa et al.)

Management of extensive lower extremity soft tissue and skin loss can be a very difficult to achieve by any surgeon. There can be several associated comorbidities that need to be considered and addressed with these patients. The approach is multifactorial and requires commitment from both the surgeon as well as the patient. There are several protocols that have been formulated throughout the literature addressing soft tissue and skin coverage of the limbs. This article provides a review of the literature and describes the evaluation, harvesting, transplantation, and management of skin grafting techniques to the lower extremities., Competing Interests: Disclosure No funding was received for this publication and there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There is an unmet need for skin grafting materials that are readily available for large area wounds, due to complex, lengthy and costly manufacturing processes that are not compatible with this type of wounds. Here we developed an acellular skin graft material based on surface coating of uncrosslinked porous (UCLP) chitosan. UCLP chitosan membranes had mechanical properties in ranges suitable for skin grafting. Polydopamine (PDA) coating improved hydrophilicity and resulted in a significant increase in attachment and metabolic activity of mammalian cells in vitro. PDA coating also decreased the attachment of pseudomonas aeruginosa - a common bacteria infecting skin wounds. Finally, the PDA-coated membranes were implanted in full thickness surgical wounds in a rodent model and resulted in complete would closure in 5 days. The current study suggests that PDA-coated UCLP chitosan membranes could be a simple and effective strategy for the development of grafting materials for large area wounds., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The use of intermediate skin substitutes between debridement and final autografting is routine for many practitioners. Materials such as xenografts and allografts have been promoted to help with wound coverage before autografting. However, there is limited data for their use in relatively small burn wounds (<10% TBSA). In this study, we analyzed the outcomes of 100 consecutive patients who underwent autografting for burns <10% TBSA at our American Burn Association-verified burn unit in the absence of intermediate skin substitute use. We retrospectively analyzed 100 patients who underwent split thickness skin graft autografting for burns <10% TBSA between November 2017 and June 2019. No patients were treated with intermediate skin substitutes. Analysis included basic demographics, comorbidities, TBSA burned, mechanism of burn, time to grafting, if grafting was performed in a single procedure or staged, graft loss (>50% graft failure), and time to complete healing (no further wound care required). Twelve patients (12%) had unpredictable graft beds, and their procedure was staged. These patients underwent surgical debridement and were dressed in antimicrobial dressing for an average of 5 days before autografting. No patients had intermediate skin substitutes between procedures. Eighty-eight patients (88%) were debrided and grafted in a single stage. In the staged group, there was a 0% rate of graft failure compared with 9.1% rate of graft failure in the primarily grafted group (P = .004). There was a similar length of stay and time to complete healing in the staged group and primarily grafted group (P = .496 and P = .571). There was a significantly shorter time from injury to first procedure between the staged group and the primarily grafted group (8.7 days and 13.5 days, P = .014). In the eight instances of graft failure, infection or inadequate debridement was the cause. Seven of these eight cases required further surgical intervention. Intermediate skin substitutes are an unnecessary step in grafting small burns. These add only complexity and cost to patient care. Many patients can be debrided and grafted in a single stage. Debridement alone with delayed grafting is a highly effective surgical method when the wound bed is not suitable for immediate grafting. The use of intermediate skin substitutes in small burns requires further investigation as this study finds low benefit for this product., (© 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.)

We aimed to evaluate the results of dermal substitute implantation after early excision in the acute phase of major burn cases within the scope of efforts to reduce contractions and scar formation in functional anatomic areas (face, neck, axilla, elbow, popliteal). Twelve patients with major burn who were treated in the burn center between September 2017 and September 2018 were included in the study. In these patients, Nevelia® dermal substitute was implanted into 24 functional areas with deep partial or full-thickness burns after surgical debridement of the wound. Autologous split-thickness skin graft was applied to these areas after 14 to 21 days. The patients were followed for 4 to 14 months (mean 6 months). Postoperative scar formation was assessed by the Vancouver Scar Scale at the end of the follow-up period. A simple qualitative staging system was used for aesthetic and functional evaluation. The time from burn injury to dermal substitute implantation was 3 to 21 days. Skin graft take was complete in 22 of 24 regions and partial in one of them, while graft loss developed in one region. In the implantation sites, the Vancouver Scar Scale ranged from 1 to 7. The aesthetic and functional evaluation showed excellent/good results in 21 of 24 anatomic regions, moderate results in 2 regions, and poor results in 1 region. The use of dermal substitute in deep burns of functional/mobile anatomic areas at the acute phase after early excision and subsequent skin autografting has opened a new alternative area in the burn surgery arena to prevent contractures and functional limitations., (© 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.)

The limited amount of donor sites and loss of dermis are major challenges in the therapy of extensively burned patients. Here, we present a complex treatment approach of an eight-year-old boy with full-thickness burns on 90% of the total body surface area, using simple and efficient techniques of tissue engineering. To obtain sufficient skin for grafting we repeatedly harvested the same anatomical areas. Acceleration of donor site healing was achieved by treatment with a suspension of noncultured autologous skin cells (NASC) and acellular porcine dermis (Xe-Derma (XD), Czech Republic). Moreover, such wound management allowed up to six reharvestings, compared with one-to-three procedures following routine treatment. Bilayer Integra template (Integra LifeSciences Corp., US) was used as the dermal substitute in over 60% of full-thickness burns. Following successful vascularisation of the neodermis in 3-4 weeks, the templates were covered with meshed split-thickness skin grafts (STSG), or Meek autografts, and facilitated by NASC/XD. We may conclude that such a 'sandwich' technique approach, combining four biological covers (Integra, STSG, NASC and XD), significantly contributed to the successful skin repair of the patient.

Purpose: This study aims to assess the efficacy and safety of Pelnac dermal regeneration template assisted by vacuum sealing drainage (VSD) and a split-thickness skin graft to cover the large skin and soft-tissue defects at foot and ankle. Methods: This study began from March 2013, up to February 2017. A total of 16 patients met the inclusion and exclusion criteria and were included. For every patient, 2 separate operations were performed, the first being thorough debridement of necrotic tissues immediate coverage of VSD at continuous negative pressure suction, and the second being the autologous split-thickness skin graft. At each follow-up, relevant data were documented. Results: The average follow-up was 16.5 months (range, 12 to 42 months). No infections, hematoma, or seroma were observed. 13 out of 16 patients had a complete skin graft "take" (100%). Patients' satisfaction of esthetic appearance was 76.5 ± 5.2/100. The VSS value was 2.2 ± 2.1, representing a good result. Regarding the sensory recovery, the response "normal or near normal" could be obtained in 14/16 patients. Mean AROM for extension/flexion of the ankle was 48.5 ± 4.8° (range 35-62°), and 93.7% (15/16) of patient could obtain a satisfying functional result. Conclusions: Our report indicated Pelnac provided an effective method for management of complex wounds with underlying bone or tendons exposed.

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.)

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.)

Objective: To explore the clinical effect of bi-layered artificial dermis combined with autologous skin graft in the repair of wounds with exposed bone and/or tendon. Methods: The medical records of 25 patients (aged 3 to 79 years, including 21 males and 4 females) with bone and/or tendon exposed wounds caused by various reasons, admitted to Nanfang Hospital of Southern Medical University from May 2014 to December 2018 were analyzed retrospectively. Of the 25 patients, 7 patients had exposed bone only, 13 patients had exposed tendon only, and 5 patients had exposure of both bone and tendon. The total wound area was 78.0 (53.4, 103.2) cm(2). The widths of bone exposure and tendon exposure were 3.2 (3.0, 3.6) cm and 2.0 (1.7, 2.4) cm, respectively. All wounds were implanted with bi-layered artificial dermis in the first stage after thorough wound debridement. After 2 to 3 weeks of vascularization of artificial dermis, autologous thin-to-medium-thickness skins or split-thickness skins were grafted to repair the wounds in the second stage. The vascularization of artificial dermis and its time, whether or not producing hematoma, the skin graft survival rate on day 7 post autologous skin grafting, whether or not repeating skin grafting, and the time of complete wound healing were observed and recorded. The patients were further followed up and observed for 3 or more months after discharge. Results: The vascularization of artificial dermis was achieved in 24 patients after the first transplantation with vascularization time being 11-21 (16±4) days. No hematoma was observed in the transplanted artificial dermis. Failed vascularization of grafted artificial dermis was observed in one patient who was later treated with negative pressure drainage and skin grafting alone, and was discharged with wound healing. The skin graft survival rate on day 7 post autologous skin grafting was 92.2%-100.0% ( (99.3±1.3)%), with the remaining wound areas recovered later by themselves or healed by dressing changes without repeated skin grafting. The complete wound healing time was 7-19 (11.9±2.8) days after autologous skin grafting. The patients were followed up for 3 to 60 months after discharge. Except for the pigmentation in skin graft area, the skin grafts survived well, being soft in texture and with no repeated ulceration, obvious hypertrophic scar, or contracture deformity. Conclusions: Artificial dermis combined with autologous skin grafting can effectively repair wounds with bone and/or tendon exposure, providing a repair strategy for this type of wounds.

Autologous split-thickness skin grafting is still an important procedure for the repair of skin defect. However, there are some obvious limitations, such as new injury to skin donor sites and insufficient skin source, etc. It is an ideal goal to develop tissue-engineered skin to realize permanent replacement of skin defect. After decades of development, a variety of tissue-engineered skins have been put into the market for applications, but it is still a long way to achieve regenerative repair of skin defect. In this article, we summarize the status of various tissue-engineered skins, and then make a preliminary discussion on the opportunities and challenges on development of tissue-engineered skin.

Background: Little is known about the efficacy of newer skin substitute scaffolds to reconstruct complex lower extremity wounds. The investigators present a multihospital experience of reconstructive surgeons utilizing collagen-GAG bilayer wound matrix in lower extremity soft-tissue reconstruction with the goals to (1) characterize a suitable patient population, (2) categorize failures to optimize patient selection, and (3) determine wound factors affecting success., Methods: Subjects underwent collagen-GAG-based lower extremity wound reconstruction from May of 2010 to June of 2017. The primary outcome variable was 180-day graft success, defined as eventual split-thickness skin grafting after bilayer wound matrix application; failure was defined as inadequate wound bed for split-thickness skin grafting, requirement for vascularized tissue transfer, or eventual amputation. Eligible subjects had at least one lower extremity wound and were at least 18 years old. Exclusion criteria included third-degree burn wounds or failure to follow up for at least 60 days postoperatively. Predictor variables included demographics, medical comorbidities, perioperative characteristics, postoperative complications, and cost-related data for each hospitalization., Results: There were 147 subjects with 191 wounds. Mean patient age was 60.1 years (range, 21.0 to 95.6 years), and mean body mass index was 30.5 kg/m (range, 14.4 to 64.7 kg/m). Average wound size was 73.1 ± 137.7 cm, with 49.0 percent of subjects receiving adjunct postoperative negative-pressure wound therapy. Seventy percent of wounds were successfully healed at 180 days. Most were localized between the knee and ankle (50.8 percent) or foot (46.1 percent). Tendon exposure (p < 0.05), bone exposure (p < 0.01), and bone excision (p < 0.04) were associated with reconstructive failure., Conclusions: The authors present the largest reported multihospital, multidisciplinary experience with collagen-GAG wound matrix for lower extremity reconstruction. Tendon and/or bone exposure and socioeconomic factors were associated with failure., Clinical Question/level of Evidence: Risk, III.

Despite the abundance of skin substitutes in the worldwide market, major hurdles in developing more complex tissues include the addition of skin appendages and vascular networks as the most important structure. The aim of this research was a clinical feasibility study of a novel prevascularized skin grafts containing the dermal and epidermal layer using the adipose stromal vascular fraction (SVF)-derived endothelial cell population for vascular network regeneration. Herein, we characterized hydrogel with emphasis on biological compatibility and cell proliferation, migration, and vitality. The therapeutic potential of the prevascularized hydrogel transplanted on five human subjects as an intervention group with diabetic wounds was compared with nonvascularized skin grafts as the control on five patients. Wound planimetric and biometric analysis was performed using a Mann-Whitney nonparametric t-test (p ≤ .05). The fibrin-collagen hydrogel was suitable for skin organotypic cell culture. There was a significant (p ≤ .05) increased in skin thickness and density in the vascular beds of the hypodermis measured with skin scanner compared with that in the control group. No significant macroscopic differences were observed between the intervention and control groups (p ≤ .05). In summary, we report for the first time the use of autologous dermal-epidermal skin grafts with intrinsic vascular plexus in a clinical feasibility study. The preliminary data showed that SVF-based full-thickness skin grafts are safe and accelerate the wound healing process. The next stage of the study is a full-scale randomized clinical trial for the treatment of patients with chronic wounds., (© 2019 John Wiley & Sons, Ltd.)

Background: Various surgical techniques exist for lower extremity reconstruction, but limited high-quality data exist to inform treatment strategies. Using multi-institutional data and rigorous matching, the authors evaluated the effectiveness and cost of three common surgical reconstructive modalities., Methods: All adult subjects with lower extremity wounds who received bilayer wound matrix, local tissue rearrangement, or free flap reconstruction were retrospectively reviewed (from 2010 to 2017). Cohorts' comorbidities and wound characteristics were balanced. Graft success at 180 days was the primary outcome; readmissions, reoperations, and costs were secondary outcomes., Results: Five hundred one subjects (166 matrix, 190 rearrangement, and 145 free flap patients) were evaluated. Matched subjects (n = 312; 104/group) were analyzed. Reconstruction success at 180 days for matrix, local tissue rearrangement, and free flaps was 69.2 percent, 91.3 percent, and 93.3 percent (p < 0.001), and total costs per subject were $34,877, $35,220, and $53,492 (p < 0.001), respectively. Median length of stay was at least 2 days longer for free flaps (p < 0.0001). Readmissions and reoperations were greater for free flaps. Local tissue rearrangement, if achievable, provided success at low cost. Free flaps were effective with large, traumatic wounds but at higher costs and longer length of stay. Matrices successfully treated older, obese patients without exposed bone., Conclusions: Lower extremity reconstruction can be performed effectively using multiple modalities with varying degrees of success and costs. Local tissue rearrangement and free flaps demonstrate success rates greater than 90 percent. Bilayer wound matrix-based reconstruction effectively treats a distinct patient population., Clinical Question/level of Evidence: Therapeutic, III.

Aim: To evaluate dermal regeneration scaffolds custom-fabricated from fibril-forming oligomeric collagen where the total content and spatial gradient of collagen fibrils was specified. Materials & methods: Microstructural and mechanical features were verified by electron microscopy and tensile testing. The ability of dermal scaffolds to induce regeneration of rat full-thickness skin wounds was determined and compared with no fill control, autograft skin and a commercial collagen dressing. Results: Increasing fibril content of oligomer scaffolds inhibited wound contraction and decreased myofibroblast marker expression. Cellular and vascular infiltration of scaffolds over the 14-day period varied with the graded density and orientation of fibrils. Conclusion: Fibril content, spatial gradient and orientation are important collagen scaffold design considerations for promoting vascularization and dermal regeneration while reducing wound contraction.

Dermal substitutes coupled with split thickness skin graft are the primary method of treating most severe full-thickness burns particularly when there is a lack of healthy donor skin. Although dermal replacements optimize functional and aesthetic outcomes in patients, the risk of infection and the amount of time required to process most dermal substitutes delay treatment potentially compromising graft take and the overall healing process. The purpose of this case series is to describe the treatment course of patients with severe burn injuries using a novel synthetic Biodegradable Temporizing Matrix (NovoSorb BTM) in conjunction with RECELL Autologous Cell Harvesting Device, a new methodology allowing for a timely point-of-care preparation of an autologous skin cell suspension in combination with a 3:1 split-thickness skin graft. To the best of our knowledge, this is the first reported case series to describe the treatment algorithm and clinical outcomes of deep full-thickness burns utilizing BTM in conjunction with RECELL ASCS., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Burn Association.)

An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations. Eight sheep fetuses of four time-mated ewes underwent fetoscopic skin biopsy at 65 days of gestation. Fibroblasts and keratinocytes isolated from the biopsy were used to create fetal dermo-epidermal skin substitutes. These were transplanted on the fetuses by open fetal surgery at 90 days of gestation on skin defects (excisional wounds) created during the same procedure. Pregnancy was allowed to continue until euthanasia at 120 days of gestation. The graft area was analyzed macroscopically and microscopically. The transplanted fetal dermo-epidermal skin substitutes was well discernable in situ in three of the four fetuses available for analysis. Histology confirmed healed grafts with a close to natural histological skin architecture four weeks after in utero transplantation. This experimental study generates evidence that laboratory grown autologous fetal skin analogues can successfully be transplanted in utero. These results have clinical implications as an analogous procedure might be applied in human fetuses undergoing prenatal repair to facilitate primary skin closure. Finally, this study may also fertilize the field of fetal tissue engineering in general, particularly when more interventional, minimally invasive, and open fetal surgical procedures become available., (© 2019 John Wiley & Sons, Ltd.)

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.)

A new model of tissue-engineered artificial autologous human skin developed in Andalusia is currently being transplanted into patients suffering from large burns within the Andalusian Public Healthcare System. This product is considered an advanced therapy medicinal product (ATMP) in Europe, and its clinical use implies meeting transplant and medicinal product legal requirements, being the Guidelines of Good Manufacturing Practice for ATMPs of particular importance. The preclinical research and clinical translation of the product have represented a technical, regulatory, and organizational challenge, which has taken 10 years since the first preclinical experiments were designed. Twelve patients with large burns, including 3 pediatric patients, have hitherto received artificial autologous skin grafts with an overall survival rate of 75% and positive clinical, homeostatic, and histologic results. Achieving such a milestone within our Healthcare System was possible through a multidisciplinary approach and the joint efforts of multiple publicly funded institutions and units under the coordination of the Andalusian Initiative for Advanced Therapies. In this article, we present the organizational model set up to facilitate collaboration and logistics among the professionals involved, totaling more than 80 people. The similarities between the tissue-engineered artificial autologous human skin transplant and other organ and tissue transplants, in terms of logistic requirements, reveal how regional and hospital transplant coordination have played a crucial role., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Artificial dermis is a kind of tissue engineering dermal substitute and is used to repair dermal defects caused by a variety of reasons. This article describes the characteristics and the mechanism of repair and reconstruction of bilayer artificial dermis. Based on domestic experience of clinical applications and relative literature of bilayer artificial dermis, more than 50 domestic experts in related field reached a consensus on indications, contraindications, operation procedures in clinical application, cautions, and treatment and prevention of complications of bilayer artificial dermis, providing reference for clinical application.

Management of third-degree facial burns remains one of the most difficult challenges in burn care. Patients with deep facial burns usually require gradual escharectomy, tangential excision of the wound, and resurfacing with full-thickness skin grafts or dermal substitutes associated with split-thickness skin grafts to provide better and superior cosmetic results. Immobilization of skin grafts and dermal substitutes by reducing shearing forces and hematoma formation underneath is paramount to improve success rates. Due to the irregular shape of the face, the proper immobilization of grafts with traditional methods is often difficult, especially over concave portions of the face. Herein, we report the original use of a custom three-dimensional printing facemask for securing dermal substitutes and skin grafts to difficult sites on the face., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The authors report their experience with the use of Integra ® dermal substitute, in combination with a thin skin graft, following an orbital exenteration. The clinical case described relates to a 42-year-old gentleman with an ulcerative retractile lesion of the right lower eyelid. Histopathological examination diagnosed a moderately differentiated epidermoid carcinoma infiltrating the orbit. Total exenteration was necessary as well as secondary radiation therapy and chemotherapy. Rehabilitation of the exenterated socket was performed by inserting an Integra ® patch, followed by an additional thin skin graft one month later. The authors review the various available techniques for exenterations, their indications and the various possible secondary rehabilitations. Despite being less utilized, the dermal substitute technique, which is relatively new, seems to offer quicker and easier rehabilitation compared to traditional techniques. A comparative study would be necessary to define superiority among the different techniques of exenteration, with respect to the speed of rehabilitation and resistance to radiation therapy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the clinical effects of artificial dermis combined with vacuum sealing drainage (VSD) and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn. Methods: A total of 8 patients with scar hyperplasia and contracture deformity on joint after healing of extensive burn were admitted to our hospital from August 2015 to August 2017. There were 5 females and 3 males aged 8 to 45 years with an average of 23 years. In the first stage operation, scar tissue on contracture site was removed, and the wound was covered by artificial dermis followed by continued VSD treatment. On 10-14 d after the first stage operation, the artificial dermis tissue formed, and the second stage autologous split-thickness skin grafting and continued VSD treatment were performed. Routine anti-scar therapy was carried out after healing of wounds. Time of wound healing after the second stage operation was recorded. Colour and texture of the split-thickness skin graft, scar formation condition of the donor site, and action condition of the operation site during follow-up were observed. Results: The wounds of 8 patients were healed in 10-14 d after the second stage operation. During follow-up of 6-24 months, the split-thickness skin graft was with smooth surface and good elasticity, and the function of joint recovered well. The donor site in head healed well with no scar. Only pigmentation was left in the donor site of thigh, and scar was not obvious. The patients and their family members were satisfied. Conclusions: After application of artificial dermis combined with VSD and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn, the skin grafting area and donor site were with unobvious scar hyperplasia, and the joint function in the operation area was good.

Cultured epithelial autografts (CEAs) represent a life-saving surgical technique for full-thickness skin burns covering more than 60% total body surface area. However, CEAs present numerous drawbacks leading to heavy cosmetic and functional sequelae. In our previous study, we showed that human plasma-based fibrin matrices (hPBM) could improve the reparative potential of CEAs. Therefore, in the present work, we sought to investigate the role of hPBM compared with fibrin from purified fibrinogen (FPF) or plastic support on epidermal substitute formation and engraftment. The use of hPBM for epidermal substitute culture improved keratinocyte migration, proliferation, and epidermal substitute organization to a better extent than FPF in vitro. Both fibrin matrices favored greater dermal-epidermal junction protein deposition and prevented their degradation. Keratinocyte differentiation was also decreased using both fibrin matrices. Basement membrane protein deposition was mainly influenced by matrix whereas growth factors released from fibrin especially by hPBM were shown to enhance in vitro keratinocyte migration, proliferation, and epidermal substitute organization. Ultimately, epidermal substitutes grown on hPBM displayed better engraftment rates than those cultured on FPF or on plastic support in a NOD-SCID model of acute wound with the formation of a functional dermal-epidermal junction. Together, these results show the positive impact of fibrin matrices and their released growth factor on epidermal substitute phenotype and grafting efficiency. Fibrin matrices, and especially hPBM, may therefore be of interest to favor the treatment of full-thickness burn patients., (© 2019 John Wiley & Sons, Ltd.)

Background: Allograft skin (AS) transplantation has been considered to be the gold standard for replacing tissue damage, following burns. However, increasingly new biosynthetic skin substitutes are being developed as alternatives. The objective of this systematic review is to compare AS with other skin substitutes, which have been used in the treatment of burns., Methods: Randomized clinical trial (RCT) and nonrandomized clinical trial (NRCT) studies comparing AS to any other skin substitute in the treatment of burns were extracted from PubMed/Medline, Scopus, EMBASE, and Web of Science. For the risk of bias analysis, the Cochrane bias risk handbook was used for RCT studies and ROBINS-1 was used for NRCT studies. Outcomes such as healing, self-grafting, scar appearance, and mortality were evaluated., Results: Twelve RCT and six NRCT were selected, with most of the methodologies presenting a high risk of bias. Based on the outcomes of the studies, it was not possible to detect any advantages for using AS, as opposed to other skin substitutes. In the meta-analysis, only two outcomes could be evaluated: healing and graft take percentage; however, no significant differences were observed between the groups., Conclusion: Because of the poor quality of the primary studies, it was not possible to identify differences in the results that compared the use of AS with other substitutes in the treatment of patients with burns. These results support the fact that surgeons primarily base the choice of skin substitute on clinical experience and cost, at least when treating burns., (Copyright © 2019 Elsevier Ltd. All rights reserved.)