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Animals such as chameleons possess a natural ability to adjust their skin color as a preventive measure to deter any potential threat and to self-heal damaged skin tissues. Inspired by this, we present here a copolymer film possessing biomimetic properties that simultaneously integrates electrochromic triphenylamine and self-healing Diels-Alder groups. The flexible and stretchable copolymer film acts like natural chameleon skin, which exhibits significant color variation and also possesses excellent self-healing properties. These remarkable features make it a promising material for overcoming the crack-generation issue inherited by conventional biomimetic chameleon skin. Moreover, a flexible and wearable skin device based on the copolymer film with silver fabric as a electrode has also been fabricated. The electrochromic and self-healing properties were verified for the copolymer film, and it has been elucidated that the intelligent biomimetic "chameleon skin" was a new step toward the development of highly advanced biomimetic materials and devices.

Split-thickness skin autografts (AGs) are the standard surgical treatment for severe burn injuries. However, the treatment of patients with substantial skin loss is limited by the availability of donor sites for skin harvesting. As an alternative to skin autografts, our research group developed autologous self-assembled skin substitutes (SASSs), allowing the replacement of both dermis and epidermis in a single surgical procedure. The aim of the study was to assess the clinical outcome of the SASSs as a permanent coverage for full-thickness burn wounds. Patients were recruited through the Health Canada's Special Access Program. SASSs were grafted on debrided full-thickness wounds according to similar protocols used for AGs. The graft-take and the persistence of the SASS epithelium over time were evaluated. 14 patients received surgical care with SASSs. The mean percentage of the SASS graft-take was 98 % (standard deviation = 5) at 5 to 7 d after surgery. SASS integrity persisted over time (average follow-up time: 3.2 years), without noticeable deficiency in epidermal regeneration. Assessment of scar quality (skin elasticity, erythema, thickness) was performed on a subset of patients. Non-homogeneous pigmentation was noticed in several patients. These results indicated that the SASS allowed the successful coverage of full-thickness burns given its high graft-take, aesthetic outcome equivalent to autografting and the promotion of long-term tissue regeneration. When skin donor sites are in short supply, SASSs could be a valuable alternative to treat patients with full-thickness burns covering more than 50 % of their total body surface area.

The skin is a “smart”, multifunctional organ that is protective, self-healing and capable of sensing and many forms of artificial skins have been developed with properties and functionalities approximating those of natural skin. Starting from specific commercial products for the treatment of burns, progress in two fields of research has since allowed these remarkable materials to be viable skin replacements for a wide range of dermatological conditions. This review maps out the development of bioengineered skin replacements and synthetic skin substitutes, including electronic skins. The specific behaviors of these skins are highlighted, and the performances of both types of artificial skins are evaluated against this. Moving beyond mere replication, highly advanced artificial skin materials are also identified as potential augmented skins that can be used as flexible electronics for health-care monitoring and other applications.

Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats. Twenty-four Wistar rats were randomly distributed into 4 groups (n = 6): (i) control-untreated; (ii) aPDT-treated with curcumin-mediated aPDT (blue light); (iii) artificial skin-treated with artificial skin alcohol-based; and (iv) aPDT plus artificial skin-treated with aPDT associated with artificial skin alcohol-based. For the in vivo model, a full-thickness biopsy with 0.80 cm was performed in order to inoculate the microorganism Staphylococcus aureus (ATCC 25923). The aPDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm

The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de novo in the epidermis or is performed with externally derived lipids. Hence, in vitro developed human skin equivalents (HSEs) are developed with culture medium that is supplemented with free fatty acids (FFAs). Nevertheless, the lipid barrier formation in HSEs remains altered compared to native human skin (NHS). The aim of this study is to decipher the role of medium supplemented saturated FFA palmitic acid (PA) on morphogenesis and lipid barrier formation in HSEs. Therefore, HSEs were developed with 100% (25 &mu, M), 10%, or 1% PA. In HSEs supplemented with reduced PA level, the early differentiation was delayed and epidermal activation was increased. Nevertheless, a similar SC lipid composition in all HSEs was detected. Additionally, the lipid organization was comparable for lamellar and lateral organization, irrespective of PA concentration. As compared to NHS, the level of monounsaturated lipids was increased and the FFA to ceramide ratio was drastically reduced in HSEs. This study describes the crucial role of PA in epidermal morphogenesis and elucidates the role of PA in lipid barrier formation of HSEs.

As a temporary skin substitute, the dressings can protect the wound, stop bleeding, prevent infection and contribute to wound healing. According to the characteristics of the materials, wound dressings can be classified into traditional wound dressings, interactive dressings, bioactive dressings, tissue engineering dressings and smart dressings, etc. Different dressings have different characteristics, and some products have been widely used in clinic. Recently nanomaterials and three-dimensional bio-printing technology have significantly improved the performance of wound dressings. Future dressings will be developed from single function to multi-function composite, and integrated into an intelligent one. This paper reviews the current research progress and future development prospects of wound dressings.敷料作为暂时性皮肤替代物可起到保护创面、止血、防止感染、促进创面愈合等重要作用。创面敷料根据材料特性可分为传统敷料、相互作用型敷料、生物活性敷料、组织工程敷料和智能敷料等。不同敷料各具特点，部分产品已被临床广泛应用。近年来纳米材料和三维打印技术的应用使创面敷料的功能显著提升，敷料的作用也由单一功能向多功能复合及智能化方向发展。本文对创面敷料的现状与发展趋势进行了综述。.

Continuous contraction of 3D skin equivalents in construction and use restricts their applications in clinical and pharmaceutical practices. So far, no effective method has been developed to inhibit such contraction. Hence, low cytotoxic cross-linkers, 1-ethyl-3-3-dimethylaminopropylcarbodiimide hydrochloride (EDC) and genipin, are investigated to reduce the contraction in this study. As found, both genipin and EDC at 0.2 and 0.4 mmol/L are nontoxic to collagen-entrapped fibroblasts and upregulate the extracellular matrix expression of fibroblasts in cross-linked collagen. Particularly, collagen cross-linking by intermediate concentrations of genipin, specifically 0.4 mmol/L, greatly reduces the contraction of 3D skin equivalents from 87% to 28% (n = 9, P

The complexity of the dermal layer of skin means that damage to this section can result in permanent impairment of function. Partial or total dermal loss is a feature of deep burns and chronic wounds such as pressure sores or diabetic ulcers. The issues posed by traditional skin grafts have led to substantial research being carried out in the fields of tissue engineering and biomaterials science to develop a vast array of alternative skin substitutes. Given the large number of different materials, manufacturing methods, and techniques for implementation described for artificial skin substitutes, many classification systems have been created to simplify their categorization. Some of these systems are oriented toward clinicians while others toward researchers. However, none address the needs of both groups and none are intuitive. The creation of an effective classification system would be particularly helpful in the regulation, distribution, organization, and selection of skin substitutes. The aim of this review is to examine existing methods of classification of skin substitutes, and to propose a new system that uses an algorithm that is inspired by factorial design. Our system allows multiple factors to be simultaneously investigated or in this case, described, since all skin substitutes possess multiple characteristics: (1) cellularity (acellular or cellular), (2) layering (single layer or bilayer), (3) replaced region (epidermis, dermis, or both), (4) materials used (natural, synthetic, or both), and (5) permanence (temporary or permanent). The factors and levels are combined into an algorithm where all the possible combinations are shown. The multifactorial and palindromic structure of our system should enable all users to quickly understand the makeup of a selected skin substitute, or search for a skin substitute depending on their specific requirements. We feel that our proposed classification can be used by clinicians and biomedical researchers alike, which should be an advantage given the multidisciplinary nature of the tissue engineering field and the science that underpins the development of skin substitutes. We also touch upon some of the state-of-the-art skin substitutes that are commercially available or under development to demonstrate how our new method of classification might work.

Burn wounds are one of the main causes of skin damage. Based on World Health Organization statistics, almost 300 000 people worldwide die of burns each year. In severe burns, the cells and blood vessels are often injured and the blood supply to the wound is disturbed. Many factors such as oxygenation, infection, aging, hormones, and nutrition potentially can influence burn progression and disrupt repair with unbalanced release of various growth factors and cytokines. Different treatment approaches such as dressings and skin substitutes have been applied to aid wound healing. A thorough understanding of the effective factors on burns can improve wound healing outcomes. This review evaluates articles published on the Scopus, EMBASE, and PubMed databases that attempt to explain the pathophysiology, molecular components, and therapeutic approaches involved in the burn wound healing process.

Our laboratory has developed a scaffold-free cell-based method of tissue engineering to produce bilayered tissue-engineered skin substitutes (TESs) from epidermal and dermal cells. However, TES pigmentation is absent or heterogeneous after grafting, due to a suboptimal number of melanocytes in culture. Our objectives were to produce TESs with a sufficient quantity of melanocytes from different pigmentation phototypes (light and dark) to achieve a homogeneous color and to evaluate whether the resulting pigmentation was photoprotective against ultraviolet radiation (UVR)-induced DNA damage in the dermis and the epidermis. TESs were cultured using different concentrations of melanocytes (100, 200, and 1,500 melanocytes/mm2 ), and pigmentation was evaluated in vitro and after grafting onto an athymic mouse excisional model. Dermal and epidermal DNA damage was next studied, exposing pigmented TESs to 13 and 32.5 J/cm2 UVR in vitro. We observed that melanocyte cell density increased with culture time until reaching a plateau corresponding to the cell distribution of native skin. Pigmentation of melanocyte-containing TESs was similar to donor skin, with visible melanin transfer from melanocytes to keratinocytes. The amount of melanin in TESs was inversely correlated to the UVR-induced formation of cyclobutane pyrimidine dimer in dermal fibroblasts and keratinocytes. Our results indicate that the pigmentation conferred by the addition of melanocytes in TESs protects against UVR-induced DNA damage. Therefore, autologous pigmented TESs could ensure photoprotection after grafting.

Diabetic foot ulcers (DFUs) are associated with an increased risk for serious and costly outcomes such as osteomyelitis, amputation, and hospitalization.A retrospective study was conducted to evaluate the proportion of patients healed and time to healing of DFUs treated with a human fibroblast-derived dermal substitute (HFDS) or a fetal bovine collagen dressing (FBCD).Data from patients with a DFU who received the first treatment in 2014 were extracted from the electronic record database of 93 wound care centers. Baseline demographics (eg, age, gender, body mass index, and number of wounds); wound location, size, and duration; and wound-specific information such as wound size and number of and interval between applications were obtained. Study criteria stipulated patients who received at least one treatment in 2014 with HFDS or FBCD on a DFU with location coded as foot, toe, heel, metatarsal head, toe web space, toe amputation site, or transmetatarsal amputation site; ulcer size ≥1 cm2 to20 cm2; and ulcer area reduction ≤50% in the 28 days before the first treatment with HFDS or FBCD were eligible for inclusion. Wounds that received an alternate skin substitute treatment up to 28 days before or concurrent with the first HFDS or FBCD treatment or if patient data that lacked baseline or follow-up wound area measurement were excluded. Deidentified data were extracted directly into data files and transferred to a third-party data management and statistical group for analysis. The frequency of DFUs achieving wound closure (defined as area ≤0.25 cm2) by weeks 12 and 24 and median time to wound closure of wounds that healed were analyzed. Baseline characteristics were compared using 2-sample t tests for continuous variables and 2-tailed Fisher's exact tests for difference in proportions between treatments. Frequency of and median time to wound closure were determined by Cox proportional hazards analysis. The frequency of wounds closed at 12 and 24 weeks, median time to wound closure, hazard ratio with 95% confidence interval, and P value were estimated from the Cox model. Statistical significance was defined as P.05.Records showed 206 patients with 208 DFUs received treatment (108 HFDS, mean age 60.2 years, mean wound duration 8.8 months; 100 FBCD, mean age 65.2 years, mean wound duration 12.8 months) and were included. Mean number of treatment applications was 4.5 and 2.4 for HFDS and FBCD, respectively. After 12 and 24 weeks 44 (41%) and 69 (64%) of HFDS-treated wounds, respectively, and 21 (21%) and 43 (43%) of FBCD-treated wounds, respectively, were healed (at 12 weeks, P = .03; at 24 weeks, P = .03, log rank 2-tailed test, unadjusted). Median time to wound closure for HFDS and FBCD was 14.6 and 25 weeks, respectively (P = .03; log rank, 2-tailed test; Kaplan-Meier analysis). HFDS treatment significantly increased the probability of wound healing compared to FBCD treatment in the Cox proportional hazards analysis after adjusting for treatment terms, baseline wound area, baseline wound duration, baseline wound depth, wound location, and patient age at first treatment (HR = 1.77; 95% CI: 1.06-2.97; P = .03).DFU wounds are more likely to heal when treated with HFDS than with FBCD as used by facilities in this database. Studies examining the efficacy, cost-effectiveness, and patient-centered outcomes of these treatments is warranted. .

Polylactic acid (PLA) nanofiber nonwovens have recently come under more vigorous investigation for their use as tissue engineering scaffolds owing to its ability to mimic the physical properties of naturally occurring human extracellular matrix in a variety of host tissues. Currently, the majority of available research on PLA nanowebs has focused on their creation through electrospinning. The goal of this study was to evaluate meltblown nonwoven webs made of nanodiameter PLA fibers for their application as a tissue engineering scaffold. Meltblown PLA fabrics were produced with a variety of different crystallinities, tensile moduli, and pore diameters. One fabric with mechanical properties similar to human dermis was selected as a scaffold to study attachment, proliferation, and migration of human dermal fibroblasts over 1, 3, 7, and 14 days without the use of additional cell adhesion molecules. The 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide assay showed good proliferation from day 1 to 3 (P = 0.026) and up to 7 days of culture (P = 0.005) but without increase from day 7 to 14. Electron microscopy demonstrated adequate cellular attachment and surface migration at 1, 3, 7, and 14 days. Finally, confocal microscopy was used to investigate cellular penetration into the scaffolds. The investigation found that cells were able to penetrate fully through the thickness of the scaffold. The successes of this initial experiment are promising and confirm that meltblown nanofiber nonwovens are a viable avenue for tissue engineering scaffolds. Hopefully, these conclusions will open the door for others to pursue research in this exciting field.

Fibroblast growth factor (FGF)-2 induces mitogenesis, angiogenesis and adipogenesis. In this study, the adipogenesis-inducing effects of FGF-2 combined with bilayer artificial dermis in mice were evaluated. FGF-2-impregnated bilayer artificial dermis composed of collagen matrix, PELNAC (Gunze Corp., Osaka, Japan) was implanted subcutaneously into the thoracic region of mice. At 1, 2, 3, and 4 weeks, samples were collected for H&E staining, von Willebrand factor immunostaining, and perilipin immunostaining to examine adipose tissue localization and angiogenesis. The collagen matrix-implanted group without the addition of FGF-2 was prepared as a control. At 2 weeks after the implantation of FGF-2 combined with dermal substitutes, adipocytes appeared in the collagen fibers. At 3–4 weeks, a fat pad was generated with neovascularization. The thickness of the fat pad had significantly increased at 2, 3, and 4 weeks. The remaining collagen was decreased by absorption over time. In the control group, no fat pad was newly formed. This study has identified a promising method to enhance adipogenic effects in the murine subcutis, representing a potential technique for soft tissue reconstruction.

Stevens-Johnson syndrome (SJS) is a disease that causes skin exfoliative lesions, characterized by fever, necrosis, and epidermal detachment. Biological skin substitutes may be considered interesting options for the treatment of this disease. This study aims at identifying in the literature the evidence on the current role of these biomaterials in the treatment of SJS and its related diseases. A systematic review with a search period between 2003 and 2017 was carried out, consulting the Lilacs, BVS, and PubMed databases. The quality of the included studies was evaluated by the Oxford Center for Evidence-Based Medicine Classification, for evaluating levels of evidence from the scientific publications. Ninety-five publications were found, and after applying inclusion and exclusion criteria, they resulted in 9 articles. In total, 20 patients with 73.87% average of body surface affected received SJS skin treatment with some biological substitutes, among them are cutaneous allograft, amnion, and xenograft. Mortality rate was 10%, and in these situations, literature indicates mortality rates ranging from 25% to 70%. Effectiveness of the use of biological dressings may be a possible explanation for this finding. Findings indicate the use of these biomaterials may favor reepithelialization, reduce water loss, decrease the chance of infection, and, consequently, improve the survival of patients with SJS and toxic epidermal necrolysis. Biological skin substitutes have characteristics that make them very promising in the topical treatment of these wounds, but their use remains very restricted in the treatment of SJS.

Chronic venous leg ulcers are responsible for significant morbidity and health care costs worldwide. This pilot study evaluated the effectiveness 2 biologically active grafts, TheraSkin and Apligraf, in conjunction with compression therapy. The study, not industry-sponsored, was designed and conducted as a prospective, head-to-head, single-site, randomized clinical trial to assess differences in healing rates, adverse outcomes, and treatment costs. The healing rates were different but not statistically significant, there were no adverse outcomes, and TheraSkin averaged $2495.33 and Apligraf averaged $4316.67 per subject. This suggests that TheraSkin may provide equivalent or superior outcomes to Apligraf while reducing costs.

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.人工真皮是一种组织工程真皮替代物，用于修复各种原因导致的真皮缺损创面。本文描述了双层人工真皮的特点及其修复重建机制。根据国内已有的双层人工真皮临床应用经验和相关文献资料，国内50余位相关领域专家就该材料的适应证、禁忌证、临床应用操作规范、注意事项及并发症的防治等达成共识，供临床应用参考。.

A self-healing electrode is an electrical conductor that can repair internal damage by itself, similar to human skin. Since self-healing electrodes are based on polymers and hydrogels, these components are still limited by low electrical conductivity and mechanical strength. In this study, we designed an electrically conductive, mechanically strong, and printable self-healing electrode using liquid crystal graphene oxide (LCGO) and silver nanowires (AgNWs). The conductive ink was easily prepared by simply mixing LCGO and AgNWs solutions. The ultrathin (3 μm thick) electrode can be printed in various shapes, such as a butterfly, in a freestanding state. The maximum conductivity and strength of the LCGO/AgNW composite were 17 800 S/cm and 4.2 MPa, respectively; these values are 24 and 4 times higher, respectively, than those of a previously developed self-healing electrode. The LCGO/AgNW composite self-healed internal damage in ambient conditions with moisture and consequently recovered 96.8% electrical conductivity and 95% mechanical toughness compared with the undamaged state. The electrical properties of the composite exhibited metallic tendencies. Therefore, these results suggest that the composite can be used as an artificial electronic skin that detects environmental conditions, such as compression and temperature. This self-healing artificial electronic skin could be applied to human condition monitoring and robotic sensing systems.

Three-dimensional (3D) porous conductive composites explored in highly sensitive tactile sensors have attracted extensive close attention in recent years owing to their peculiar porous structure and unique physical properties in terms of excellent mechanical flexibility, high relative dielectric permittivity, and good elastic property. Herein, we report an practical, efficient, and macroscopic dip-coating process to manufacture rapid-response, low detection limit, high-sensitivity, and highly sensitive capacitive flexible tactile sensors. The fabrication process, tactile perception mechanism, and sensing performance of the developed devices are comparatively investigated. The homogeneous 3D hybrid network constructed by graphene nanoplatelets/carboxyl-functionalized multiwalled carbon nanotubes/silicone rubber composites anchored on polyurethane sponge skeletons exhibits a significantly improved dielectric property, resulting in a high-performance capacitive flexible tactile sensor with a fast response time (∼45 ms), an extremely low-pressure detection limit of ∼3 Pa, excellent sensitivity (∼0.062 kPa-1), and excellent durability and stability over 2000 cycles. Importantly, the flexible devices can be used as the wearable electronic skin and successfully mounted on human skin or a soft-bodied robot to achieve the capability of physiological stimuli monitoring, micropressure monitoring, soft grabbing, etc. Our rapid-response, low detection limit, and high-sensitivity capacitive flexible tactile sensor with a novel 3D porous dielectric layer could be a prospective candidate for the wearable applications in real-time and high-accuracy portable healthcare monitoring devices, advanced human-machine interfaces, and intelligent robot perception systems.

Tactile sensing is the current challenge in robotics and object manipulation by machines. The robot&rsquo, s agile interaction with the environment requires pressure sensors to detect not only location and value, but also touch direction. The paper presents a new, two-layer construction of artificial robotic skin, which allows measuring the location, value, and direction of pressure from external force. The main advantages of the proposed solution are its low cost of implementation based on two FSR (Force Sensitive Resistor) matrices and real-time operation thanks to direction detection using fast matching algorithms. The main contribution is the idea of detecting the pressure direction by determining the shift between the pressure maps of the skin&rsquo, s upper and lower layers. The pressure map of each layer is treated as an image and registered using a phase correlation (POC&ndash, Phase Only Correlation) method. The use of the developed device can be very wide. For example, in the field of cooperative robots, it can lead to the improvement of human machine interfaces and increased security of human&ndash, machine cooperation. The proposed construction can help meet the increasing requirements for robots in cooperation with humans, but also enable agile manipulation of objects from their surroundings.

Acral lentiginous melanoma is the most common subtype among melanomas on the foot. Reconstruction of a wide surgical defect once it is excised may result in a challenge that requires replacing the lost tissue with another tissue having similarly unique physical characteristics. Although reconstructive options such as skin grafts and either local or distant flaps offer adequate coverage, they often are subject of contraction, muscle atrophy, and contour abnormalities. Dermal substitutes provide support and structure and recreates the dermal layer to ensure a durable reconstruction. We report 2 cases of plantar melanoma in which adequate reconstruction was achieved using a dermal substitute.

Summary Background While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge. Objectives To perform biological characterization of self‐assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi). Methods Fibroblast subpopulations were cultured with ascorbic acid to promote cell‐assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell‐depleted ECMs to generate epidermal‐only skin constructs. Results We found that the ECM self‐assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi‐derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation. Conclusions We argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications., What's already known about this topic? There are several types of skin fibroblasts within the dermis that can be defined by their spatial location: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).Extracellular matrix (ECM) composition is distinct with regard to composition and architecture within the papillary, reticular and hair follicle dermis in vivo.When skin is injured, dermal replacement substitutes used for tissue repair do not reflect the heterogeneity observed within the skin dermis. What does this study add? Self‐assembled ECMs from different subpopulations of skin fibroblasts can be generated in vitro.Cell‐assembled ECMs made in vitro from Pfi, Rfi and DPfi reflect dermal heterogeneity seen in vivo and are morphologically, functionally and compositionally distinct from one another.Inspiration should be taken from cell‐assembled ECMs from distinct fibroblast subpopulations, to improve the design of therapeutic biomaterials in skin engineering applications. What is the translational message? Cell‐assembled ECMs from DPfi and Pfi, but not Rfi, can support formation of a basement membrane in adjacent keratinocytes in vitro.Inspiration should be taken from cell‐assembled ECMs from distinct fibroblast subpopulations, to improve the design of therapeutic biomaterials in skin engineering applications. Linked Comment: https://doi.org/10.1111/bjd.16773. https://doi.org/10.1111/bjd.16946 available online https://goo.gl/Uqv3dl

We isolated and identified yeasts from burn wounds and evaluated the ability of Candida parapsilosis isolates from burn wounds to penetrate an acellular dermal matrix (ADM). A prospective study was conducted with patients from the burn treatment center of North Parana University Hospital in Londrina, Brazil from February 2015 to January 2016. Yeast cultures were obtained from the tissue of burn wounds that had been debrided and cleansed with 2% chlorhexidine. After identification and confirmation of the purity of the culture, the yeasts were placed on ADM fragments and incubated for three or seven days. During the study period, 273 patients were treated, and 36 of these patients fulfilled the inclusion criteria and provided samples for culture. Yeasts were isolated in 19.44% (n = 7) of the cultures, and the following species were identified: C. parapsilosis (57.1%), C. albicans (28.6%), and C. glabrata (14.3%). C. parapsilosis, the most frequent species, was chosen for the ADM tests. We demonstrated active penetration of the ADM by the yeast isolates from burn wounds. C. parapsilosis grew on ADM and penetrated the matrix, indicating that this yeast, which is common in skin and cutaneous wounds, has the potential to colonize and pass through ADM, a medical device that is frequently used to dress and regenerate burn wounds.

Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds. Statement of Significance Development of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.

Double layer dermal substitute (DS) consist of a 3‐dimensional collagen structures and a superficial silicon layer that are positioned within the defect provide to promote tissue regeneration in skin wounds. DS often have unique physical characteristics due to differences in manufacturing techniques. The aim of this study is the clinical and histological comparison of Nevelia and Integra double layer DSs in patients with post‐traumatic injury wounds. Thirty patients with post‐traumatic wounds localised on the inferior limbs were randomised in 2 groups Nevelia or Integra, followed by autologous dermal epidermal graft (DEG). Clinical results were evaluated through the healing time; Manchester Scar Scale (MSS) and Visual Analog Scale (VAS) at 1, 2, and 3 weeks and after 1 and 3 years. Histological and immunohistochemical evaluation were performed at 0, 2, and 3 weeks. The difference in healing time between groups (P = .467, log‐rank test), pain and self‐estimation was not statistically significant after 35, 42, and 49 days and at 1‐year follow up. Histological data showed evident healing of wound after 2 weeks compared with preoperative with both DSs. At 3 weeks reepithelialisation and dermal regeneration were evident with both substitutes; however Nevelia showed early regenerative properties in terms of epidermal proliferation and dermal renewal compared with Integra. Nevelia showed also a more evident angiogenesis vs Integra evaluated as α‐SMA immunohistochemistry. Differences in the MSS score were statistically significant at 3 years follow up in favour of Nevelia group (P = .001). At long‐term follow up, Nevelia showed a better clinical outcome measured as MSS score vs Integra measured as MSS. Histological and immunohistochemistry data showed that Nevelia allows faster neoangiogenesis and tissue regeneration with neoformed tissue architecture closer to the physiology of the skin.

Direct application of amnion has greater risk of immunological rejection and infection. Decellularization is an effective method to lower the risk of immune complications and infections. The bioreactor assembly with multiple cassettes was designed for decellurization of multiple amnions with different cell types simultaneously in single run. A detergent-based protocol was modified to remove all cellular components from amnion and diminish the DNA content to render it non-immunogenic. Amnion (n = 10) were treated with 2% sodium dodecyl sulphate (SDS), 5% dimethyl sulfoxide (DMSO) and 2% sodium deoxycholeate (SD). Decellularized amnion samples were analyzed by haematoxylin-eosin staining (HE), Alcian blue pH 1 (AB-pH-1), 4,6-diamnionidino-2-phenylindol (DAPI), Massion's trichrome stain, DNA quantification, mechanical testing and scanning electron microscopy (SEM). Histological analysis showed complete removal of cellular components and the histoarchitecture of scaffold remained intact. Amnion scaffold activated with platelet rich plasma (PRP) and calcium chloride composition supported better adherence to the wound than amnion alone. Only single application showed good healing. In vivo assessment of activated amnion revealed stable dressing. It has good promising outcome. At day 7, histologically the wounds treated with activated amnion were almost closed without scarring and showed well differentiated epidermis, proliferation of keratinocytes, hair follicles and basement membrane as compared to controls and silver nitrate gel dressings in a mouse (Mus musculus). Cryopreservation had no adverse effect on the mechanical properties of the amnion scaffold. Cryopreservation of decellularized amnion by Dulbecco's modified eagle medium (DMEM) was expected to prepare off-the-shelf skin substitutes and preserve them to be immediately available upon request of patients' needs.

Artificial "electronic skin" is of great interest for mimicking the functionality of human skin, such as tactile pressure sensing. Several important performance metrics include mechanical flexibility, operation voltage, sensitivity, and accuracy, as well as response speed. In this Letter, we demonstrate a large-area high-performance flexible pressure sensor built on an active matrix of 16 × 16 carbon nanotube thin-film transistors (CNT TFTs). Made from highly purified solution tubes, the active matrix exhibits superior flexible TFT performance with high mobility and large current density, along with a high device yield of nearly 99% over 4 inch sample area. The fully integrated flexible pressure sensor operates within a small voltage range of 3 V and shows superb performance featuring high spatial resolution of 4 mm, faster response than human skin (30 ms), and excellent accuracy in sensing complex objects on both flat and curved surfaces. This work may pave the road for future integration of high-performance electronic skin in smart robotics and prosthetic solutions.

Surgical sutures have different sizes, structures, whereas they are being used for various surgeries. The high friction performance of surgical sutures in the suturing process may cause inflammation and pain, leading to a longer recovery time. This paper presents an understanding of the tribological behavior of surgical suture with monofilament and multifilament structures, by means of a penetration friction apparatus (PFA). The results indicated that structure and surface topography of the surgical suture had a pronounced effect on the tribological interactions. It was found that the friction force and abrasion area of skin substitute with the penetration of polyglycolic acid (PGA) multifilament surgical suture were larger than that of Nylon monofilament surgical suture. Meanwhile, more abrasion at the pull-in boundary of skin substitute was observed compared with that at the pull-out boundary.

We have developed an artificial skin that mimics the morphological and mechanical properties of human skin. The artificial skin comprises a polyurethane block possessing a microscopically rough surface. We evaluated the tactile sensations when skin-care cream was applied to the artificial skin. Many subjects perceived smooth, moist, and soft feels during the application process. Cluster analysis showed that these characteristic tactile feels are similar to those when skin-care cream is applied to real human skin. Contact angle analysis showed that an oil droplet spread smoothly on the artificial skin surface, which occurred because there were many grooves several hundred micrometers in width on the skin surface. In addition, when the skin-care cream was applied, the change in frictional force during the dynamic friction process increased. These wetting and frictional properties are important factors controlling the similarity of artificial skin to real human skin.

Dermal substitutes are frequently used for the initial coverage of extensive skin defects. The seeding of these implants with adipose tissue-derived microvascular fragments (ad-MVF) has recently been shown to accelerate their vascularization and incorporation. In the present study we analyzed whether these processes are affected by a thromboprophylactic therapy with the low molecular weight heparin (LMWH) enoxaparin (enox). Green fluorescent protein (GFP)+ ad-MVF were isolated from enox- (8 mg/kg s.c.) and vehicle-treated (0.9% NaCl s.c.) (C57BL/6-Tg(CAG-EGFP)1Osb/J mice and seeded onto Integra matrices. Subsequently, these were implanted into full-thickness skin defects within dorsal skinfold chambers of enox- and vehicle-treated C57BL/6 wild-type mice. Repetitive stereomicroscopy and intravital fluorescence microscopy over 2 weeks as well as histological and immunohistochemical analyses on day 14 revealed that enox does not inhibit the reassembly of ad-MVF into new microvascular networks. In addition, treatment with the anticoagulative compound did not promote implant-induced hemorrhage formation. Accordingly, Integra matrices in enox- and vehicle-treated animals exhibited a comparable final microvessel density, fraction of GFP+ blood vessels originating from seeded ad-MVF, collagen fiber content, and epithelialization. These novel findings demonstrate that the seeding of dermal substitutes with ad-MVF may be applied also during thromboprophylactic therapy without affecting implant vascularization and bleeding risk.

Sensors are essential in the haptic technology of soft robotics, which includes the technology of humanoids. Haptic sensors can be simulated by the mimetic organ of perceptual cells in the human body. However, there has been little research on the morphological fabrication of cutaneous receptors embedded in a human skin tissue utilizing artificial materials. In the present study, we fabricated artificial, cell-like cutaneous receptors embedded in skin tissue mimicking human skin structure by utilizing rubber. We addressed the fabrication of five cutaneous receptors (free nerve endings, Krause and bulbs, Meissner corpuscles, Pacinian corpuscles and Ruffini endings). In addition, we investigated the effectiveness of the fabricated tissue for mechanical and thermal sensing. At first, in the production of integrated artificial skin tissue, we proposed a novel magnetic, responsive, intelligent, hybrid fluid (HF), which is suitable for developing the hybrid rubber skin. Secondly, we presented the fabrication by utilizing not only the HF rubber but our previously proposed rubber vulcanization and adhesion techniques with electrolytic polymerization. Thirdly, we conducted a mechanical and thermal sensing touch experiment with the finger. As a result, it demonstrated that intelligence as a mechanoreceptor or thermoreceptor depends on its fabric: the HF rubber sensor mimicked Krause and bulbs has the thermal and pressing sensibility, and the one mimicked Ruffini endings the shearing sensibility.

There is accumulating evidence that interactions between epidermal melanocytes and stromal cells play an important role in the regulation of skin pigmentation. In this study we established a pigmented dermo-epidermal skin model, melDESS, of human origin to investigate the effects of distinct stromal cells on melanogenesis. melDESS is a complex, clinically relevant skin equivalent composed of an epidermis containing both melanocytes and keratinocytes. Its dermal compartment consists either of adipose tissue-derived stromal cells, dermal fibroblasts (Fbs), or a mixture of both cell types. These skin substitutes were transplanted for 5 weeks on the backs of immuno-incompetent rats and analyzed. Gene expression and Western blot analyses showed a significantly higher expression of transforming growth factor-β1 by adipose tissue-derived stromal cells compared with dermal Fbs. In addition, we showed that melanocytes responded to the increased levels of transforming growth factor-β1 by down-regulating the expression of key melanogenic enzymes such as tyrosinase. This caused decreased melanin synthesis and, consequently, greatly reduced pigmentation of melDESS. The conclusions are of utmost clinical relevance, namely that adipose tissue-derived stromal cells derived from the hypodermis fail to appropriately interact with epidermal melanocytes, thus preventing the sustainable restoration of the patient's native skin color in bioengineered skin grafts.

It is a significant challenge to regenerate full-thickness skin defects with sweat glands. Various skin substitutes have been developed to resolve this issue with minimal success. In this study, to yield a novel construct for in situ regeneration of sweat glands, the collagen-chitosan porous scaffold was combined with Lipofectamine 2000/pDNA-EGF complexes to obtain the gene-activated scaffold (GAS), which was then seeded with bone marrow-derived mesenchymal stem cells (BM-MSCs). The porous scaffold functionalized as a reservoir for the incorporated gene complexes which were released in a sustained manner. The seeded BM-MSCs were transfected in situ by the released complexes and specially differentiated into sweat gland cells in vitro under the induction of the expressed epidermal growth factor (EGF). Application in vivo of the GAS/BM-MSCs constructs on the full-thickness skin defects of SD rats confirmed that GAS/BM-MSCs could accelerate the wound healing process and induce the in situ regeneration of the full-thickness skin with sweat gland-like structures. Analyzed by immunohistochemical staining, RT-qPCR and Western-blotting, the levels of the major sweat gland markers such as carcino-embryonic antigen (CEA), cytokeratin 8 (CK8) and cytokeratin 14 (CK14) were all up-regulated, indicating that GAS/BM-MSCs can facilitate the regeneration of sweat glands-like structure in vivo.

Purpose/Aim of the study: Chlorhexdine has been shown to provide excellent and cost-effective presurgical antisepsis. However, standard presurgical concentrations of chlorhexidine (2-4%) are known to cause ocular injury, even in cases in which a bio-occlusive dressing (Tegaderm™) was applied beforehand to the closed eye.Three experiments were conducted to assess the barrier performance of Tegaderm™ to chlorhexidine skin prep in vitro and on non-ocular skin. The experiments used water as a control group.In the first in vitro experiment, the chlorhexidine group showed penetration at the edges of the Tegaderm™ at 5 minutes while the water (control) group never penetrated the Tegaderm™. A subsequent experiment testing the central permeability of the tegaderm showed it to be impermeable to both chlorhexidine and water after 90 minutes. In the in vivo experiment, the chlorhexidine group showed penetration at 10 minutes, while the water (control) group never penetrated the Tegaderm™.These data suggest Tegaderm™ is permeable at the edges to chlorhexidine but not water. Based on this, along with reports of ocular injury from chlorhexidine skin preparation of the head despite prior application of Tegaderm™ over the eyes, we advise against using bio-occlusive adhesive dressing to protect the ocular surface from chlorhexidine exposure. We suggest an alternative presurgical antiseptic agent such as povidone-iodine be employed whenever possible.

Flexible skin-mimicking electronics are highly desired for development of smart human-machine interfaces and wearable human-health monitors. Human skins are able to simultaneously detect different information, such as touch, friction, temperature, and humidity. However, due to the mutual interferences of sensors with different functions, it is still a big challenge to fabricate multifunctional electronic skins (E-skins). Herein, a combo temperature-pressure E-skin is reported through assembling a temperature sensor and a strain sensor in both of which flexible and transparent silk-nanofiber-derived carbon fiber membranes (SilkCFM) are used as the active material. The temperature sensor presents high temperature sensitivity of 0.81% per centigrade. The strain sensor shows an extremely high sensitivity with a gauge factor of ∼8350 at 50% strain, enabling the detection of subtle pressure stimuli that induce local strain. Importantly, the structure of the SilkCFM in each sensor is designed to be passive to other stimuli, enabling the integrated E-skin to precisely detect temperature and pressure at the same time. It is demonstrated that the E-skin can detect and distinguish exhaling, finger pressing, and spatial distribution of temperature and pressure, which cannot be realized using single mode sensors. The remarkable performance of the silk-based combo temperature-pressure sensor, together with its green and large-scalable fabrication process, promising its applications in human-machine interfaces and soft electronics.

OBJECTIVE Innovative skin substitutes and temporary wound dressings are frequently used in the treatment of superficial and partial-thickness wounds. The aim of this study was to compare 2 commonly used temporary skin dressings with a newly developed collagen matrix to determine changes in microcirculation as measured by blood flow, hemoglobin oxygenation, and relative hemoglobin values during healing of partial-thickness skin defects. METHODS This animal study involved 28 adult male Lewis rats. On the back of each rat, 2 standardized partial-thickness skin defects were generated through a skin dermatome (n = 56). Then, wounds were treated with polylactide-based copolymer skin substitute (Suprathel, PolyMedics, Denkendorf, Germany; n = 14), biosynthetic skin dressing (Biobrane, Smith & Nephew, Hamburg, Germany; n = 14), or Collagen Cell Carrier (CCC; Naturin Viscofan, Weinheim, Germany; n = 14). The remaining control wounds were left untreated (n = 14). MAIN OUTCOME MEASURES Perfusion dynamics were assessed every 10 days for 80 days with the O2C device (LEA Medizintechnik, Gieβen, Germany) to determine blood flow, hemoglobin oxygenation, and relative amount of hemoglobin. MAIN RESULTS Blood flow was increased in all wounds for at least 30 days after wound generation. The relative amounts of hemoglobin were increased in superficial layers (2 mm) for 10 to 20 days. Hemoglobin oxygenation in the superficial layers decreased in the polylactide-based copolymer skin substitute and biosynthetic skin dressing-treated groups and initially increased in the untreated wounds and CCC groups on day 10; these values also decreased. CONCLUSIONS The presented results demonstrate the complex changes in microcirculation in the course of healing partial-thickness wounds with different wound dressings and contribute to a better understanding of these wounds. However, based on the results of the study, a clear recommendation for a specific substitute is not yet possible.

BACKGROUND/PURPOSE During the injection of a fluid in a tissue model, the fluid might be affected by the needle tip configuration and the number of channels. Thus, the objective of the present work is to observe the influence of different needle tips and number of channels on the spread of a fluid. METHODS Fluid distribution data were obtained after injecting 0.3 mL of fluid into a foamed polymer model with a velocity of 2 mm/s. The spread area and the depth were determined for 3 different types of hypodermic needles: Single channel needles with bevel tip and blunt tip and a needle with conical tip and 3 internal channels. RESULTS The bevel tip provides a higher spread in the direction where the bevel points and reaches larger depths than the other two needles. The spread for the blunt tip and the polymer needle is equally distributed on both sides of the needle. The largest horizontal area around the tip is achieved by the 3-channel needle. CONCLUSION The tip configuration and number of channels have an influence on the distribution of fluid. The bevelled needle directs the fluid and reaches larger depths compared with the 3-channel needle that gets more horizontal spread.

3D texture morphing for camouflage Some animals, such as cephalopods, use soft tissue to change shape reversibly for camouflage and object manipulation. Pikul et al. used fixed-length fiber mesh embedded in a silicone elastomer to transform a flat object into a 3D structure by inflating membranes (see the Perspective by Laschi). Painted models of rocks and plants were also created that could be morphed to fully blend into their surroundings. Science , this issue p. 210 ; see also p. 169

Skin regeneration is impeded by a host of factors. Working out the part played by each could lead to fresh approaches to treating burns and scars. Skin regeneration is impeded by a host of factors. Working out the part played by each could lead to fresh approaches to treating burns and scars.

Nanofiber-based artificial skin has shown promising applications in flexible wearable electronics due to its favorable breathability and comfortable wearability. However, the commonly used electrospinning method for nanofiber preparation suffers from poor spinning ability for ionotronic solutions. Moreover, the membrane usually lacks self-adhesive and self-adapting properties when attaching to an irregular subject, which greatly hinders its practical usage. Herein, a self-adhesive and contractile silk fibroin/graphene nano-ionotronic skin was successfully prepared by using a high yield electro-blown technique. The electro-blown technique could effectively overcome the instability of the spinning jet and raise the feeding rate to at least 5 mL h-1. The high Ca2+ content provided the fabricated nano-ionotronic skin with humidity-induced stretchability and robusticity. More importantly, the ionotronic skin also possessed self-adhesive property and could contract to adapt to irregular surfaces. Additionally, due to the well-dispersed graphene sheets among the silk nanofiber skeleton, the obtained nano-ionotronic skin showed stable conductivity in various humidity conditions, indicating its excellent potential for application as highly stretchable strain sensors. Furthermore, an analytical piezoresistive model was successfully built to predict the response of the sensors to stress. The design and manufacture concept proposed in this work might inspire the development of high yield ionotronic nanofibers and the design of self-adapting artificial skin.

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.

To advance drug development representative reliable skin models are indispensable. Animal skin as test model for human skin delivery is restricted as their properties greatly differ from human skin. In vitro 3D-human skin equivalents (HSEs) are valuable tools as they recapitulate important aspects of the human skin. However, HSEs still lack the full barrier functionality as observed in native human skin, resulting in suboptimal screening outcome. In this review we provide an overview of established in-house and commercially available HSEs and discuss in more detail to what extent their skin barrier biology is mimicked in vitro focusing on the lipid properties and cornified envelope. Further, we will illustrate how underlying factors, such as culture medium improvements and environmental factors affect the barrier lipids. Lastly, potential improvements in skin barrier function will be proposed aiming at a new generation of HSEs that may replace animal skin delivery studies fully.

Large skin wounds pose a major clinical challenge. Scarcity of donor site and postsurgical scarring contribute to the incomplete or partial loss of function and aesthetic concerns in skin wound patients. Currently, a wide variety of skin grafts are being applied in clinical settings. Scaffolds are used to overcome the issues related to the misaligned architecture of the repaired skin tissues. The current review summarizes the contribution of biomaterials to wound healing and skin regeneration and addresses the existing limitations in skin grafting. Then, the clinically approved biologic and synthetic skin substitutes are extensively reviewed. Next, the techniques for modification of skin grafts aiming for enhanced tissue regeneration are outlined, and a summary of different growth factor delivery systems using biomaterials is presented. Considering the significant progress in biomaterial science and manufacturing technologies, the idea of biomaterial-based skin grafts with the ability for scarless wound healing and reconstructing full skin organ is more achievable than ever.