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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%).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.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).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.

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 cm2 refrigerated tissue; cohort 2, ≤440 cm2 refrigerated tissue; and cohort 3, ≤440 cm2 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.

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.

Summary Background Dermal regenerative matrices (DRMs) have been used for several decades in the treatment of acute and reconstructive burn injury. The objective of this study was to perform a systematic review of the literature to assess clinical outcomes and safety profile of DRMs in full-thickness burn injury. Methods Comprehensive searches of MEDLINE, EMBASE, CINAHL, and Cochrane Library were performed from 1988 to 2017. Two independent reviewers completed preliminary and full-text screening of all articles. English-language articles reporting on DRM use in patients with full-thickness burn injury were included. Results Literature search generated 914 unique articles. Following screening, 203 articles were assessed for eligibility, and 72 met inclusion criteria for analysis. DRM was applied to1084 patients (74% acute burns, 26% burn reconstruction). Of the twelve studies that described changes in ROM, significant improvement was observed in 95% of reconstructive patients. The most frequently treated reconstructive sites were the neck, hand/wrist, lower extremity, and axilla. Vancouver scar scale was used in eight studies and indicated a significant improvement in the scar quality with DRM. The overall complication rate was 13%, most commonly infection, graft loss, hematoma formation, and contracture. Conclusions Although variability in functional and cosmetic outcomes was observed, DRM demonstrates improvements in ROM and scar appearance without objective regression. Essential demographic data were lacking in many studies, highlighting the need for future standardization of reporting outcomes in burns following application of dermal substitutes.

BackgroundOne Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs.MethodsOne hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed ‘spray-on’ skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed.DiscussionOutpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.

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

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.

Supplemental digital content is available in the text., OBJECTIVE To investigate differences in wound-related costs; product waste; lower-extremity amputations; and number of applications, hospitalizations, and emergency room visits among patients treated with three cellular and/or tissue-based products. METHODS This retrospective intent-to-treat matched-cohort study analyzed the full Medicare claims dataset from 2011 to 2014. Patients who received either a bilayer cellular construct (BLCC), dermal skin substitute (DSS), or cryopreserved human skin allograft (CHSA) were concurrently matched for Charlson Comorbidity Index, age, sex, and region, resulting in 14,546 study patients. Key variables were reported at 60, 90, and 180 days after the first product application. RESULTS There were no statistically significant differences in the distribution of Charlson Comorbidity Index, age, sex, and region among cohorts. Wound-related costs and product wastage were lower for CHSA patients relative to both BLCC and DSS patients at all time intervals (P < .05). Patients treated with CHSA received fewer product applications than DSS at 90 and 180 days (P < .05). Amputations were significantly higher among patients treated with DSS than either CHSA or BLCC (P < .0001). CONCLUSIONS The data demonstrate that wound-related costs, product waste, amputations, and frequency of applications are lower for CHSA than DSS. Wound-related costs and product waste are lower for CHSA compared with BLCC. Further claims analysis and prospective clinical trials could help develop appropriate quality measures and reimbursement models to ensure smarter spending for the growing population of patients with chronic wounds.

The use of bioengineered skin has facilitated fundamental and applied research because it enables the investigation of complex interactions between various cell types as well as the extracellular matrix. The predominantly manual fabrication of these living tissues means, however, that their quality, standardization, and production volume are extremely dependent on the technician's experience. Simple laboratory automation could facilitate the use of living tissues by a greater number of research groups. We developed and present here an injection molding technique for the fabrication of bilayered skin equivalents. The tissue was formed automatically by two separate injections into a customized mold to produce the dermal and epidermal skin layers. We demonstrated the biocompatibility of this fabrication process and confirmed the resulting bilayered morphology of the bioengineered skin using histology and immunohistochemistry. Our findings highlight the possibility of fabricating multilayered living tissue by injection molding, suggesting that further investigation into this automation method could result in the rapid and low-cost fabrication of standardized bioengineered skin.

Full-thickness wounds are difficult to heal spontaneously. Scaffolds, meant for treating full-thickness wounds, should ensure proper tissue regeneration, both structurally and functionally. An ideal scaffold should mimic the physical, mechanical and biochemical properties of natural skin. However, available mono- or bi-layer skin scaffolds lack in the precise architecture and functionality, thus, failing to provide scar-free regeneration of full-thickness skin wounds. These unmet challenges of scar-free skin regeneration have been addressed in the present study for the first time. This research deals with the synthesis of a low-cost, structurally and functionally graded single unit biodegradable polymeric scaffold. The functional gradient in this scaffold was achieved by varying polymer concentration and electrospinning parameters. This gradient in the scaffold provided the required microenvironment for proper functional and structural reconstruction of all the layers of natural skin. The mechanical property of the scaffold matched that of the natural skin. Besides, the degradation kinetics of the scaffold was in coordination with the regeneration time for the full-thickness wound. The porosity and hydrophilicity gradients of the scaffold helped it mimic the in vivo hypodermal, dermal and epidermal microenvironments of the skin, simultaneously. Co-culturing PCS-201 (dermal fibroblasts) and HaCaT (keratinocytes) on the scaffold resulted in successful regeneration through cellular proliferation, differentiation and organization of the skin tissue. The scaffold also displayed better wound healing in vivo, in terms of speedy wound closure and proper tissue regeneration, in comparison to the standard treatment. Altogether, this study successfully established a simple, one-step synthesis process of a functionally graded, bioresorbable scaffold for scar-free, native-like, structural and functional regeneration of full-thickness skin wounds. Due to cost-effectiveness, easy synthesis process and microarchitectural features, the designed scaffold possesses a potential of translation to a good commercial wound healing product.

Background and objectives: The skin recently became the main focus of regenerative medicine and, in this context, skin substitutes are fully entering into the plastic surgeon’s armamentarium. Among the various types of skin substitutes, dermal substitutes (DSs) are the most used. Our study aims to retrospectively compare three renowned and extremely similar DS in the management of critical lower limb wounds in the largest cohort analysis currently present in literature. Materials and Methods: We followed a strict protocol of application and evaluation of the DS for each patient and wound and, after a meticulous bias reduction process, we compared final outcomes in terms of efficacy and speed in achieving the defect coverage. Results: Among patients who did not receive a skin graft after the DS, we registered a wound healed surface of 50% for Pelnac, 52% for Integra, and 19% for Nevelia, after 30 days from the external silicon layer removal; among those who received a skin graft after the DS, we observed a significantly lower mean percentage of graft take after 7 days with Pelnac (53%) compared to Integra and Nevelia (92% and 80%, respectively). The overall percentage of wound healed surface obtained after 30 days from the external silicon sheet removal, either with or without skin graft, was 71% for Pelnac, 63% for Integra and 63% for Nevelia. We also ran a sub-group analysis only including grafted wounds with a negative microbiological test and the mean percentage of graft take was similar this time. Eventually, we assessed the influence of the wound’s “chronicity” on its healing, comparing the mean graft take only in “acute” wounds who received a skin graft and it resulted 63% for Pelnac, 91% for Integra and 75% for Nevelia. Conclusions: Integra demonstrates the highest rate of skin graft viability and the highest rate of skin graft takes after 7 days. Pelnac shows the quickest induction of secondary healing in acute wounds. Nevelia is not different from Integra and shows a superior graft take compared to Pelnac, but features the lowest secondary healing induction rate. No differences exist between the three DSs in terms of wound healing after 30 days from the skin graft or from the removal of the external silicon layer.

Estimating the Center of Pressure (CoP) under legged robots is useful to control their posture and gait. This is traditionally done using contact sensors at the base of the foot or with sensors on distal joints, which are subject to wear and damage due to impulse forces. In vertebrates, skin and ligament deformation at the ankle is a particularly rich source of sensory information for locomotion. For our bipedal mechanism, afferent signals from sensors on synthetic skin wrapped around the ankles sufficed to estimate the location of the CoP with a mean accuracy81.5%. For this we used K-Nearest Neighbors (KNN) algorithm trained on the same force magnitude applied at four and nine ground-truth CoP locations. For a single mechanical foot (i.e., single stance), signals from skin or ligaments (i.e., elastic rubber sheets and cables, respectively) also sufficed to calculate the CoP (Mean prediction accuracy91.3%). Moreover, the visco-elasticity of these elements serves to passively stabilize the ankle. Importantly, training the single leg case with forces of different magnitudes also resulted in similarly accurate mean CoP prediction accuracy84.5%. We show that using bio-inspired proprioceptive skins and/or ligament arrangements can provide reliable COP predictions, while permitting arbitrary postures of the ankle and no sensors on the sole of the foot prone to wear and damage. This novel approach to estimation of the CoP can be used to improve locomotion control in a new class of bio-inspired rigid, soft and hybrid (soft-rigid) legged robots.

Increasing biomechanical applications of skin-inspired devices raise higher requirements for the skin-bionic robustness and environmental compatibility of elastomers. Here, a tough and degradable self-healing elastomer (TDSE) is developed by a synergistic soft-hard segments design. The polyester/polyether copolymer is introduced in soft segments to endow TDSE with flexibility and degradability. The two isomeric diamines are regulated in hard segments for elevating the toughness and fracture energy to 82.38 MJ/m3 and 43299 J/m2 and autonomous self-healing ability with 93% efficiency in 7 h for the TDSE. Employing TDSE and ionic liquid, a biomechano-robust artificial skin (BA-skin) is constructed with a stretch-insensitive mechanosensation capability during 50% cyclic stretching. The BA-skin has high biomechano-robustness to bear tear damage and good environmental compatibility with total decomposability in a lipase solution. This work provides a molecular design guideline for high-performance skin-bionic elastomers for applications in skin-inspired devices.

Healthy skin moLEdels produced by tissue-engineering often present a suboptimal skin barrier function as compared with normal human skin. Moreover, skin substitutes reconstructed according to the self-assembly method were found to be deficient in polyunsaturated fatty acids (PUFAs). Therefore, in this study, we investigated the effects of a supplementation of the culture media with docosahexaenoic acid (DHA) on the barrier function of skin substitutes. To this end, 10 μM DHA-supplemented skin substitutes were produced (n = 3), analyzed, and compared with controls (substitutes without supplementation). A Franz cell diffusion system, followed by ultra-performance liquid chromatography, was used to perform a skin permeability to testosterone assay. We then used gas chromatography to quantify the PUFAs found in the epidermal phospholipid fraction of the skin substitutes, which showed successful DHA incorporation. The permeability to testosterone was decreased following DHA supplementation and the lipid profile was improved. Differences in the expression of the tight junction (TJ) proteins claudin-1, claudin-4, occludin, and TJ protein-1 were observed, principally a significant increase in claudin-1 expression, which was furthermore confirmed by Western blot analyses. In conclusion, these results confirm that the DHA supplementation of cell culture media modulates different aspects of skin barrier function in vitro and reflects the importance of n-3 PUFAs regarding the lipid metabolism in keratinocytes.

Lack of matrix deposition is one of the main factors that complicates the healing process of wounds. The aim of this study was to test the efficacy and safety of a liquid dermal scaffold, referred to as MeshFill (MF), that can fill the complex network of tunnels and cavities which are usually found in chronic wounds and hence improve the healing process. We evaluated the in vitro and in vivo properties of a novel liquid dermal scaffold in a delayed murine full thickness wound model. We also compared this scaffold with two commercially- available granular collagen-based products (GCBP). Liquid dermal scaffold accelerated wound closure significantly compared to no-treated control and collagen-based injectable composites in a delayed splinted wound model. When we compared cellular composition and count between the MF, no treatment, and GCBP at the histology level, it was found that MF was the most analogous and consistent to the normal anatomy of the skin. These findings were matched with the clinical outcome observation. The flowable in situ-forming scaffold is liquid at cold temperature and gels after application to the wound site. Therefore, it would conform to the topography of the wound when liquid and provides adequate tensile strength when solidified. This patient-ready gelling dermal scaffold also contains the nutritional ingredients and therefore supports cell growth. Applying an injectable liquid scaffold that can fill wound gaps and generate a matrix to promote keratinocytes and fibroblasts migration, can result in improvement of the healing process of complex wounds.

Complex cutaneous wounds resulting from disease and trauma can be difficult to heal and may require advanced treatment options. Split-thickness skin grafts (STSGs) and other biologic allogeneic and xenogeneic skin substitutes are limited in their ability to manage these lesions, and STSGs may also be limited in availability. A synthetic hybrid-scale fiber matrix, engineered with an architecture similar to native extracellular matrix, has been shown to have excellent durability and does not carry the risks of disease transmission or inflammatory response associated with biologic materials; it may offer a new option for managing these complex wounds. In this preliminary study, the synthetic matrix was used to treat 3 patients with difficult-to-treat wounds, including lesions associated with calciphylaxis, enteroatmospheric abdominal fistula, and necrotizing fasciitis of the hand with exposed tendon. Treatment with the synthetic matrix resulted in significant reepithelialization and wound healing. The successful results suggest that the synthetic matrix enables healing of complex cutaneous wounds and may be a reasonable alternative to STSG, even in particularly challenging cases.

Burn injuries commonly result in serious sequelae (such as skin contractures) in surviving patients, for which no single optimal solution is known. The goal of this study was to compare the late contraction of autologous skin grafts with or without dermal matrices used in the treatment of patients with burn contractures. This parallel design prospective, randomised and controlled clinical trial included patients with burn contracture treated using autologous skin grafts and dermal matrix. Patients were randomly assigned to one of the four groups: Integra® matrix (n = 10), Pelnac® matrix (n = 10), Matriderm® matrix (n = 9) or a Control Group (n = 10, without dermal matrix, only skin graft). The boundaries of skin defect were marked and transferred to a flat sterile surface for area measurement. The current area of the skin grafts was measured during surgery and compared with those obtained at 1, 3, 6 and 12 months postoperatively. Twelve months after surgery, the Control Group presented lower rates of skin graft contraction than Integra® (p 0.01), Matriderm® (p = 0.01) and Pelnac® (p 0.01) groups. Pelnac® resulted in larger skin graft contraction than Matriderm® (p 0.01) and Integra® (p = 0.02), while differences between Integra® and Matriderm® were not significant (p = 0.16). The comparison between intraoperative and 12 months after surgery showed that the worst mean rates of skin graft contraction were from the Pelnac® (51.79%) and Matriderm® (59.17%). In patients with burn contractures, the use of these three dermal matrices did not reduce or avoid the occurrence of late contraction of the skin graft, so their use for this purpose should be carefully evaluated.

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.

Regeneration of large acute and chronic wounds is a concern worldwide. The present study evaluates wound healing competence of a completely human-origin, extracellular matrix (ECM)-based skin substitute/graft. It comprises cell-less amniotic membrane (AM), clinical-grade fibrin (FIB), and hyaluronic acid (HA) termed as AMFIBHA. The use of large-area third-degree rabbit burn wounds evaluated the product efficiency. The AMFIBHA induces hemostasis and permits suture-less positioning on the wound bed. In wet wounds, the AMFIBHA degrades and release biologically active molecules and guide cell migration, proliferation, and regeneration. The study demonstrated the effectiveness of this wound care product in terms of epithelial-dermal regeneration with angiogenesis. The study assessed injury-associated inflammation and different wound healing markers after 28 days of experiment and compared with both positive and negative controls-treated wounds. The regeneration of mature epidermis and dermis with rete pegs and hair follicle-like structure was evident upon a single application. The active involvement of host cells resulted in supple tissue formation. The ECM organization of AMFIBHA-treated tissue resulted in re-gain of mechanical properties comparable to native skin after 56 days. These guided regenerative outcomes reveal a promising translational value of the novel AMFIBHA skin substitute as an off-the-shelf product for clinical use.

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

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.

The mechanical properties of artificial skins are complicated to maintain under ensuring air permeability and antimicrobial. Thus, a series of hydrophilic antimicrobial polymer networks are prepared by crosslinking chitosan and polyvinyl alcohol with the lauramidopropyl betaine and hydrogen bond organic framework (CS/PVA/LPB/2D-HOF). The mechanical performance of the control groups and the complex are systematically evaluated to attain an artificial strength skin. The CS/PVA/LPB/2D-HOF complex exhibits strong mechanical abilities than other control groups. By analyzing the IR spectra and the morphology, the synergistic effect of hydrogen bonds between molecules and cracks significantly improves the mechanical properties of the complex. Its maximum tensile strength can reach 29 MPa, and its maximum load capacity can reach 3700 g. Notably, the composite membrane also performs an excellent antimicrobial activity. In vivo and in vitro experiments show that the hybrid membrane can promote tissue regeneration and wound healing (95％). These results may open up the opportunity for future composite material investigations in the artificial skin and tissue engineering field.

Thermal injuries may cause significant damage to large areas of the skin. Extensive and deep burn wounds require specialized therapy. The optimal method in the strategy of treating extensive, full thickness burns (III°) is the use of autologous split thickness skin grafts STSG (Busuioc et al. Rom J Morphol Embryol 4:1061-1067, 2012; Kitala D, Kawecki M, Klama-Baryła A, Łabuś W, Kraut M, Glik J, Ryszkiel I, Kawecki MP, Nowak M. Allogeneic vs. Autologous Skin Grafts in the Therapy of Patients with Burn Injuries: A Restrospective, Open-label Clinical Study with Pair Matching. Adv Clin Exp Med. 2016 Sep-Oct;25(5):923-929.; Glik J, Kawecki M, Kitala D, Klama-Baryła A, Łabuś W, Grabowski M, Durdzińska A, Nowak M, Misiuga M, Kasperczyk A. A new option for definitive burn wound closure - pair matching type of retrospective case-control study of hand burns in the hospitalized patients group in the Dr Stanislaw Sakiel Center for Burn Treatment between 2009 and 2015. Int Wound J. 2017 Feb 21. https://doi.org/10.1111/iwj.12720 . [Epub ahead of print]; Prim et al. May 24Wound Repair Regen., 2017; Grossova et al. Mar 31Ann Burns Fire Disasters 30:5-8, 2017). The main limitation of that method is the inadequate amount of healthy, undamaged skin (donor sites), which could be harvested and used as a graft. Moreover, donor sites are an additional wounds that require analgesic therapy, leave scars during the healing process and they are highly susceptible to infection (1-6). It must be emphasized that in terms of the treatment of severe, deep and extensive burns, and there should be no doubt that the search for a biocompatible skin substitute that would be able to replace autologous STSG is an absolute priority. The above-mentioned necessitates the search for new treatment methods of severe burn wounds. Such methods could consider the preparation and application of bioengineered, natural skin substitutes. At present, as the clinical standard considered by the physicians may be use of available biological skin substitutes, e.g., human allogeneic skin, in vitro cultured skin cells, acellular dermal matrix ADM and revitalized ADMs, etc. (Busuioc et al. Rom J Morphol Embryol 4:1061-1067, 2012; Kitala D, Kawecki M, Klama-Baryła A, Łabuś W, Kraut M, Glik J, Ryszkiel I, Kawecki MP, Nowak M. Allogeneic vs. Autologous Skin Grafts in the Therapy of Patients with Burn Injuries: A Restrospective, Open-label Clinical Study with Pair Matching. Adv Clin Exp Med. 2016 Sep-Oct;25(5):923-929.; Glik J, Kawecki M, Kitala D, Klama-Baryła A, Łabuś W, Grabowski M, Durdzińska A, Nowak M, Misiuga M, Kasperczyk A. A new option for definitive burn wound closure - pair matching type of retrospective case-control study of hand burns in the hospitalised patients group in the Dr Stanislaw Sakiel Center for Burn Treatment between 2009 and 2015. Int Wound J. 2017 Feb 21. https://doi.org/10.1111/iwj.12720 . [Epub ahead of print]; Prim et al. May 24Wound Repair Regen., 2017; Grossova et al. Mar 31Ann Burns Fire Disasters 30:5-8, 2017; Łabuś et al. FebJ Biomed Mater Res B Appl Biomater 106:726-733, 2018).

To investigate how suturing orange and banana peels, pig skin, and synthetic skin compares with the experience of suturing human skin.Interventional study of simple interrupted, vertical mattress, and subcuticular suturing on the four test materials.Fifteen consultants and six trainees in surgical and emergency medicine specialties at a New South Wales regional teaching hospital.The primary outcome was completion of simple interrupted, vertical mattress, and subcutaneous sutures. Secondary outcomes (assessed in a questionnaire) were similarity of suturing each material to suturing human skin, suitability of each material for practising each suture type, and similarity of each material to human anatomic skin types.All 21 participants completed simple interrupted sutures in bananas and pig and synthetic skins, and 15 in orange skin (P = 0.002). All 21 participants completed vertical mattress sutures in pig and synthetic skins, 18 in bananas, and six in oranges (P 0.001). The numbers of completed subcuticular sutures were lower for the two fruits (orange, zero; banana, two) than for pig and synthetic skins (each, 21; P 0.001). Banana peel was rated as somewhat similar to human skin and recommended for practising simple interrupted and vertical mattress suturing.Bananas are not only useful as healthy snacks between theatre cases, but also for practising and improving simple and vertical mattress suturing skills. However, less portable and nourishing materials are required for subcuticular suturing practice, such as pig skin or synthetic skin.

Human skin architecture comprises several interpenetrating macromolecules seen as organized extracellular matrix (ECM). For regeneration of critical-size acute and chronic wounds, substituting the damaged tissue with artificially assembled biomolecules offer an interactive milieu. This study reports development and preclinical evaluation of a biodegradable and immuno-compatible scaffold for regeneration of critical-size (4 × 4 cm2) full-thickness rabbit burn wounds. The designed wound care product comprises synthetic terpolymer poly(L-Lactide-co-Glycolide-co-Caprolactone) (PLGC), human clinical-grade fibrin (FIB), and hyaluronic acid (HA), termed as PLGCFIBHA. Here, clotting of fibrinogen concentrate (FC) with excess thrombin in the scaffold create an interpenetrating FIB network harnessed with adhesive molecules like fibronectin and laminin present in FC with exogenous HA to produce ECM-like milieu on porous PLGC. Penetrating into porous PLGCFIBHA, long term study showed a regulated fibroblast growth resulting in non-fibrotic dermal-like tissue in vitro. The freeze-dried PLGCFIBHA with residual thrombin facilitated suture-less, hemostatic matrix adhesion to the wound bed in vivo. By 28 d, mature and scar-less epidermis-dermis formation with skin appendages was evident in the PLGCFIBHA-treated wound area. Both negative (untreated/sham) and positive (commercial matrix-treated) control wounds showed incomplete regeneration. The PLGCFIBHA-treated wounds were comparable to native skin by 56 d. These regenerative outcomes upon single application of PLGCFIBHA confirms its potential translational value for wound care.

Significance: Artificial skin (AS) is widely used in dermatology, pharmacology, and toxicology, and has great potential in transplant medicine, burn wound care, and chronic wound treatment. There is a great demand for high-quality AS product and a non-invasive detection method is highly desirable. Aim: To quantify the constructure parameters (i.e., thickness and surface roughness) of AS samples in the culture cycle and explore the growth regularities using optical coherent tomography (OCT). Approach: An adaptive interface detection algorithm is developed to recognize surface points in each A-scan, offering a rapid method to calculate parameters without constructing OCT B-scan pictures and further achieving realizing real-time quantification of AS thickness and surface roughness. Experiments on standard roughness plates and H&E-staining microscopy were performed as a verification. Results: As applied on the whole cycle of AS culture, our method’s results show that during the air–liquid culture, the surface roughness of the skin first decreases and then exhibits an increase, which implies coincidence with the degree of keratinization under a microscope. And normal and typical abnormal samples can be differentiated by thickness and roughness parameters during the culture cycle. Conclusions: The adaptive interface detection algorithm is suitable for high-sensitivity, fast detection, and quantification of the interface with layered characteristic tissues, and can be used for non-destructive detection of the growth regularity of AS sample thickness and roughness during the culture cycle.

This work introduces an array prototype based on a Frequency Modulation (FM) encoding architecture to transfer multiple sensor signals on a single wire. The use case presented adopts Hall-effect sensors as an example to represent a much larger range of sensor types (e.g., proximity and temperature). This work aims to contribute to large area artificial skin systems which are a key element to enhance robotic platforms. Artificial skin will allow robotic platforms to have spatial awareness which will make interaction with objects and users safe. The FM-based architecture has been developed to address limitations in large-scale artificial skin scalability. Scalability issues include power requirements, number of wires needed, as well as frequency, density, and sensitivity bottlenecks. In this work, eight sensor signals are simultaneously acquired, transferred on a single wire and decoded in real-time. The overall taxel array current consumption is 36 mA. The work experimentally validates and demonstrates that different input signals can be effectively transferred using this approach minimizing wiring and power consumption of the taxel array. Four different tests using single as well as multiple stimuli are presented. Observations on performances, noise, and taxel array behaviour are reported. The results show that the taxel array is reliable and effective in detecting the applied stimuli.

Synthetic macroporous biomaterials are widely used in the field of skin tissue engineering to mimic membrane functions of the native dermis. Biomaterial designs can be subclassified with respect to their shape in fibrous designs, namely fibers, meshes or fleeces, respectively, and porous designs, such as sponges and foams. However, synthetic matrices often have limitations regarding unfavorable foreign body responses (FBRs). Severe FBRs can result in unfavorable disintegration and rejection of an implant, whereas mild FBRs can lead to an acceptable integration of a biomaterial. In this context, comparative in vivo studies of different three-dimensional (3D) matrix designs are rare. Especially, the differences regarding FBRs between synthetically derived filamentous fleeces and sponge-like constructs are unknown. In the present study, the FBRs on two 3D matrix designs were explored after 25 days of subcutaneous implantation in a porcine model. Cellular reactions were quantified histopathologically to investigate in which way the FBR is influenced by the biomaterial architecture. Our results show that FBR metrics (polymorph-nucleated cells and fibrotic reactions) were significantly affected according to the matrix designs. Our findings contribute to a better understanding of the 3D matrix tissue interactions and can be useful for future developments of synthetically derived skin substitute biomaterials.

Ultrafast artificial skin enables unprecedented tactile internet applications in prosthetics, robotics, and human-machine interactions. However, current artificial skin systems that rely on front-end interface electronics typically perform redundant data transfer and analogue-to-digital conversions for decision-making, causing long latency (milliseconds). Here, a near-sensor analogue computing system based on a flexible memristor array for artificial skin applications is reported. This system, which seamlessly integrates a tactile sensor array with a flexible hafnium oxide memristor array, can simultaneously sense and compute raw multiple analogue pressure signals without interface electronics. As a proof-of-concept, the system is used for real-time noise reduction and edge detection of tactile stimuli. One sensing-computing operation of this system takes about 400 ns and consumes on average 1000 times less power than a conventional interface electronic system. The results demonstrate that near-sensor analogue computing offers an ultrafast and energy-efficient route to large-scale artificial skin systems. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version The project was partially supported by the National Key R&D Program of China under Grant (2021YFB3601200), the National Nature Science Foundation of China (62104042), the Agency for Science, Technology and Research (A*STAR) under its AME Programmatic Funding Scheme (Project #A18A1b0045), the National Research Foundation (NRF), Prime Minister’s office, Singapore, under its NRF Investigatorship (NRF-NRFI2017-07), and Singapore Ministry of Education (MOE2019-T2-2-022).