Search

Objective: The skin is a complex organ that includes various stem cell populations. Current approaches for non-healing skin defects are sometimes inadequate and many attempts have been made to regenerate skin integrity. The aim of this review is to bridge the gap between basic research and clinical application of skin integrity regeneration. Methods: A literature search was carried out in PubMed using combinations of the keywords “skin integrity”, “tissue-engineered skin”, “bioengineered skin”, and “skin regeneration”. Articles published from 1968 to 2023 reporting evidence from in vivo and in vitro skin regeneration experiments were included. Results: These articles showed that stem cells can be differentiated into normal skin cells, including keratinocytes, and are a significant source of skin organoids, which are useful for investigating skin biology; and that emerging direct reprogramming methods have great potential to regenerate skin from the wounded skin surface. Conclusion: Recent advances in skin regeneration will facilitate further advancement of both basic and clinical research in skin biology.

Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta (TGF-β) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF-β, a signaling molecule with diverse cellular functions. Approach: The TGF-β receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF-β. Skin scaffold samples, grouped into three categories (control, TGF-β-treated, and TGF-β + galunisertibtreated), were prepared in two distinct culture media--one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results: Results showed significantly higher wave speed (with AP, p < 0.001; without AP, p < 0.001) and Brillouin frequency shift (with AP, p < 0.001; without AP, p = 0.01) in TGF-β-treated group compared with the control group. The difference in wave speed between the control and TGF-β + galunisertib with (p = 0.10) and without AP (p = 0.36) was not significant. Moreover, the TGF-β + galunisertibtreated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF-β-treated group without AP, further strengthening the potential role of TGF-β in regulating the mechanical properties of the samples. Conclusions: These findings offer valuable insights into TGF-β-induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. Methods: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. Results: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. Conclusions: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies. [ABSTRACT FROM AUTHOR]

The treatment of skin trauma, especially facial skin trauma, is a major challenge due to its complex structure, the presence of appendages, color, texture, and the large area to be reconstructed in extensive trauma. “The gold standard” for treating trauma is autologous intermediate thickness skin grafting. An alternative solution is the usage of bioengineered skin substitutes. Tissue engineering is intended to provide patients with better treatment options and more effective pain reduction. Unique skin lesions are those related to the face. To fulfill the need to improve the results of facial skin reconstruction, the “Biomask” concept was introduced for the treatment of facial wounds. The purpose of this review is to analyze composite dermal-epidermal substitutes already on the market for clinical use, as well as briefly discussing materials in the testing phase, focusing on 3D skin bioprinting and facial trauma regeneration using “BioMask”. PubMed and Google Scholar databases were searched for relevant sources. Search terms included “skin substitutes”, “synthetic skin substitutes”, “bioengineered skin”, “composite skin substitutes” and additionally each analyzed unit of composite skin substitutes was searched. Bioengineered skin substitutes effectively fulfill the role of dressings during the reconstruction of skin injuries. The development of 3D skin bioprinting is enabling the increasing and effective use of these materials. The high requirements in the treatment of facial skin injuries are the trigger for the development of new materials such as "BioMask". The synergy of new technologies makes it possible to create improved methods of wound dressing and reconstruction of skin defects.

Diabetic foot ulcers (DFUs) pose a significant threat to individuals with diabetes mellitus (DM), such as lower limb amputation and severe morbidity. Bioengineered skin substitutes (BSS) are alternatives to traditional interventions for treating DFUs, but their efficacy compared to standard wound care (SWC) or other treatment types, such as allografts, remains unknown. A scoping review of human studies was conducted to identify current approaches in the treatment of DFUs using BSS as compared with other treatment options. Systematic searches in PubMed, Cochrane Library, and Web of Science were conducted to identify comparative studies that enrolled 10 or more patients and evaluated wound healing outcomes (closure, time-to-healing, and area reduction). Database searches isolated articles published from 1 December 2012 to 1 December 2022 and were conducted in accordance with PRISMA-ScR guidelines. The literature search yielded 1312 articles, 24 of which were included for the qualitative analysis. Findings in these studies demonstrated that BSS outperformed SWC in all measured outcomes, suggesting that BSS may be a superior treatment for DFUs. Of the 24 articles, 8 articles compared human amniotic membrane allografts (hAMA) to BSS. Conflicting evidence was observed when comparing BSS and hAMA treatments, highlighting the need for future research. [ABSTRACT FROM AUTHOR]

Timely intervention of preventative and therapeutic measures abated a 2022 mpox global outbreak. However, the high transmissibility and unique pathological characteristics of mpox demand further investigation. Here, we discuss the potentials of human skin-on-a-chip as a valuable model for mpox disease evaluation, to achieve in-depth physiological understanding and desirable therapeutic predictive capabilities. [ABSTRACT FROM AUTHOR]

Objective: The skin is a complex organ that includes various stem cell populations. Current approaches for non-healing skin defects are sometimes inadequate and many attempts have been made to regenerate skin integrity. The aim of this review is to bridge the gap between basic research and clinical application of skin integrity regeneration., Methods: A literature search was carried out in PubMed using combinations of the keywords "skin integrity", "tissue-engineered skin", "bioengineered skin", and "skin regeneration". Articles published from 1968 to 2023 reporting evidence from in vivo and in vitro skin regeneration experiments were included., Results: These articles showed that stem cells can be differentiated into normal skin cells, including keratinocytes, and are a significant source of skin organoids, which are useful for investigating skin biology; and that emerging direct reprogramming methods have great potential to regenerate skin from the wounded skin surface., Conclusion: Recent advances in skin regeneration will facilitate further advancement of both basic and clinical research in skin biology., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s).)

The most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200–280 nm), -B (280–315 nm), and -A (315–400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development. The epidermis of the bioartificial skin substitute was able to mature and differentiate in a time-dependent manner, expressing relevant molecules able to absorb most of the incoming UV radiation. Absorbance spectral behavior of the skin substitutes showed similar patterns to control native skin (VAF > 99.4%), with values 0.85–0.90 times lower than control values at 7 and 14- days and 1.05–1.10 times the control values at 21- and 28-days. UV absorbance increased, and UV transmission decreased with culture time, and comparable results to the control were found at 21 and 28 days. These findings support the use of samples corresponding to 21 or 28 days of development for clinical purposes due to their higher histological similarities with native skin, but also because of their absorbance of UV radiation. [ABSTRACT FROM AUTHOR]

Dermal fibroblasts are the most accessible cells in the skin that have gained significant attention in cell therapy. Applying dermal fibroblasts' regenerative capacity can introduce new patterns to develop cell‐based therapies to treat skin disorders. Dermal fibroblasts originate from mesenchymal cells and are located within the dermis. These cells are mainly responsible for synthesizing glycosaminoglycans, collagens, and components of extracellular matrix supporting skin's structural integrity. Preclinical studies suggested that allogeneic and autologous dermal fibroblasts provide widespread and beneficial applications for wound healing, burn ulcers, and inherited skin disorders. In this regard, generating induced pluripotent stem cells (iPSCs) from fibroblasts and gene‐edited fibroblasts are promising approaches for treating skin disorders. Here, we aimed to review literature about ongoing and completed clinical trials that applied fibroblasts and bioengineered fibroblasts as therapeutic agents for various skin disorders. This review explores cell therapy protocols from the earliest phase of allogeneic and autologous fibroblasts development in different benches to translating them into bedside‐level treatment for skin disorders, particularly recessive dystrophic epidermolysis bullosa. [ABSTRACT FROM AUTHOR]

The most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200–280 nm), -B (280–315 nm), and -A (315–400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development. The epidermis of the bioartificial skin substitute was able to mature and differentiate in a time-dependent manner, expressing relevant molecules able to absorb most of the incoming UV radiation. Absorbance spectral behavior of the skin substitutes showed similar patterns to control native skin (VAF > 99.4%), with values 0.85–0.90 times lower than control values at 7 and 14- days and 1.05–1.10 times the control values at 21- and 28-days. UV absorbance increased, and UV transmission decreased with culture time, and comparable results to the control were found at 21 and 28 days. These findings support the use of samples corresponding to 21 or 28 days of development for clinical purposes due to their higher histological similarities with native skin, but also because of their absorbance of UV radiation.

As the largest organ in the human body, the skin has the function of maintaining balance and protecting from external factors such as bacteria, chemicals, and temperature. If the wound does not heal in time after skin damage, it may cause infection or life-threatening complications. In particular, medical treatment of large skin defects caused by burns or trauma remains challenging. Therefore, human bioengineered skin substitutes represent an alternative approach to treat such injuries. Based on the chemical composition and scaffold material, skin substitutes can be classified into acellular or cellular grafts, as well as natural-based or synthetic skin substitutes. Further, they can be categorized as epidermal, dermal, and composite grafts, based on the skin component they contain. This review presents the common commercially available skin substitutes and their clinical use. Moreover, the choice of an appropriate hydrogel type to prepare cell-laden skin substitutes is discussed. Additionally, we present recent advances in the field of bioengineered human skin substitutes using three-dimensional (3D) bioprinting techniques. Finally, we discuss different skin substitute developments to meet different criteria for optimal wound healing. [ABSTRACT FROM AUTHOR]

Autologous skin grafts are used to treat severe burn wounds, however, the availability of adequate donor sites makes this option less practical. Recently, stem cells have been used successfully in tissue engineering and in regenerative medicine. The current study aims to differentiate umbilical cord tissue derived mesenchymal stem cells (CT-MSCs) into skin cells (fibroblasts and keratinocytes) for use to treat severe burn wounds. After isolation, MSCs were characterized and their growth characteristics were determined. The cells were induced to differentiate into fibroblasts and keratinocytes using respective induction medium. Results indicated that CT-MSCs were spindle shaped, plastic adherent and positive for CD29, CD44, CD73, CD90 markers. CT-MSCs also showed high proliferative potential as indicated by cumulative population doubling, doubling time and plating efficiency. The MSCs were successfully differentiated into fibroblast and keratinocytes as indicated by morphological changes and expression of lineage specific genes. We propose that these differentiated skin cells which are derived from CT-MSCs can thus be used for the development of bioengineered skin; however, further studies are required to evaluate the utility of these substitutes.

Wound healing is a complex restorative process of the altered cutaneous tissue, which is impaired by numerous local and systemic factors, leading to chronic non-healing lesions with few efficient therapeutic options. Stem cells possess the capacity to differentiate into various types of cell lines. Furthermore, stem cells are able to secrete cytokines and growth factors, modulating inflammation and ultimately leading to angiogenesis, fibrogenesis, and epithelization. Because of their paracrine activity, these cells are able to attract other cell types to the base of the wound, improving the formation of new skin layers. Mesenchymal stem cells derived from the adipose tissue, bone marrow, and placenta, offer numerous ways of implementation. The process of harvesting, growing, and administrating stem cells depends on the site and type of the cells, but recent trial results showed improvement of wound healing independent of the administration site. Bioengineered skin substitutes are validated for treatment of chronic wounds with direct application on the skin surface. These offer physical scaffolding for the migrating cells and promote secretion of growth factors, thus facilitating rapid wound healing. Obtaining further clinical data is essential, but stem cell therapy may become a first-line therapeutic choice for the treatment of non-healing chronic wounds.

Selective cell death by apoptosis plays important roles in organogenesis. Apoptotic cells are observed in the developmental and homeostatic processes of several ectodermal organs, such as hairs, feathers, and mammary glands. In chick feather development, apoptotic events have been observed during feather morphogenesis, but have not been investigated during early feather bud formation. Previously, we have reported a method for generating feather buds on a bioengineered skin from dissociated skin epithelial and mesenchymal cells in three‐dimensional culture. During the development of the bioengineered skin, epithelial cavity formation by apoptosis was observed in the epithelial tissue. In this study, we examined the selective epithelial cell death during the bioengineered skin development. Histological analyses suggest that the selective epithelial cell death in the bioengineered skin was induced by caspase‐3‐related apoptosis. The formation of feather buds of the bioengineered skin was disturbed by the treatment with a pan‐caspase inhibitor. The pan‐caspase inhibitor treatment suppressed the rearrangement of the epithelial layer and the formation of dermal condensation, which are thought to be essential step to form feather buds. The suppression of the formation of feather buds on the pan‐caspase inhibitor‐treated skin was partially compensated by the addition of a GSK‐3β inhibitor, which activates Wnt/β‐catenin signaling. These results suggest that the epithelial cell death is involved in the formation of feather buds of the bioengineered skin. These observations also suggest that caspase activities and Wnt/β‐catenin signaling may contribute to the formation of epithelial and mesenchymal components in the bioengineered skin. In this study, we examined an epithelial cell death during the bioengineered skin development. This study suggests that the epithelial cell death is involved in the formation of feather buds of the bioengineered skin. Our observations also suggest the possibility that caspase activities and Wnt/β‐catenin signaling may contribute to the formation of epithelial and mesenchymal components in the bioengineered skin. [ABSTRACT FROM AUTHOR]

As the largest organ in the human body, the skin has the function of maintaining balance and protecting from external factors such as bacteria, chemicals, and temperature. If the wound does not heal in time after skin damage, it may cause infection or life-threatening complications. In particular, medical treatment of large skin defects caused by burns or trauma remains challenging. Therefore, human bioengineered skin substitutes represent an alternative approach to treat such injuries. Based on the chemical composition and scaffold material, skin substitutes can be classified into acellular or cellular grafts, as well as natural-based or synthetic skin substitutes. Further, they can be categorized as epidermal, dermal, and composite grafts, based on the skin component they contain. This review presents the common commercially available skin substitutes and their clinical use. Moreover, the choice of an appropriate hydrogel type to prepare cell-laden skin substitutes is discussed. Additionally, we present recent advances in the field of bioengineered human skin substitutes using three-dimensional (3D) bioprinting techniques. Finally, we discuss different skin substitute developments to meet different criteria for optimal wound healing.

Progress in understanding and treating metastatic melanoma is the result of decades of basic and translational research as well as the development of better in vitro tools for modeling the disease. Here, we review the latest therapeutic options for metastatic melanoma and the known genetic and non-genetic mechanisms of resistance to these therapies, as well as the in vitro toolbox that has provided the greatest insights into melanoma progression. These include next-generation sequencing technologies and more complex 2D and 3D cell culture models to functionally test the data generated by genomics approaches. The combination of hypothesis generating and hypothesis testing paradigms reviewed here will be the foundation for the next phase of metastatic melanoma therapies in the coming years. [ABSTRACT FROM AUTHOR]

In skin tissue engineering, surface feature of the scaffolds plays an important role in cell adhesion and proliferation. In this study, non-woven fibrous substrate based on poly (lactic-co-glycolic acid) (PLGA) (75/25) were hydrolyzed in various concentrations of NaOH (0.05 N, 0.1 N, 0.3 N) to increase carboxyl and hydroxyl groups on the fiber surfaces. These functional groups were activated by EDC/NHS to create chemical bonding with collagen. To improve bioactivity, the activated substrates were coated with a collagen solution (2 mg/ml) and cross-linking was carried out using the EDC/NHS in MES buffer. The effectiveness of the method was evaluated by contact angle measurements, porosimetry, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), tensile and degradation tests as well as in vitro cell attachment and cytotoxicity assays. Cell culture results of human dermal fibroblasts (HDF) and keratinocytes cell line (HaCat) revealed that the cells could attach to the scaffold. Further investigation with MTT assay showed that the cell proliferation of HaCat significantly increases with collagen coating. It seems that sufficient stability of collagen on the surface due to proper chemical bonding and cross-linking has increased the bioactivity of surface remarkably which can be promising for bioengineered skin applications. [ABSTRACT FROM AUTHOR]

Extensive skin loss and chronic wounds are still a significant challenge to clinicians: even if injured epidermis is normally able to self-renew, deep injuries can cause negative regulation of the wound healing cascade, leading to chronic wound formation. Skin-autografting surgical procedures are often limited by the poor availability of healthy tissue, whereas the use of non-self-tissues for allografts presents some severe risks. Tissue-engineered skin substitutes have recently become viable as a suitable alternative to auto- and allografts. However, biologists, biochemists, and technical engineers are still struggling to produce complex skin substitutes that can readily be transplanted in large quantities. The ambitious goal is now to construct a dermoepidermal substitute that rapidly vascularizes and optimally supports a stratifying epidermal graft on a biodegradable matrix. This review analyzes these aspects in light of the available literature and the authors’ experience. [ABSTRACT FROM AUTHOR]

We present an in vitro model of human skin that, together with nonlinear optical microscopy, provides a useful system for characterizing morphological and structural changes in a living skin tissue microenvironment due to changes in oxygen status and proteolytic balance. We describe for the first time the effects of chronic oxygen deprivation on a bioengineered model of human interfollicular epidermis. Histological analysis and multiphoton imaging revealed a progressively degenerating ballooning phenotype of the keratinocytes that manifested after 48 h of hypoxic exposure. Multiphoton images of the dermal compartment revealed a decrease in collagen structural order. Immunofluorescence analysis showed changes in matrix metalloproteinase (MMP)-2 protein spatial localization in the epidermis with a shift to the basal layer, and loss of Ki67 expression in proliferative basal cells after 192 h of hypoxic exposure. Upon reoxygenation MMP-2 mRNA levels showed a biphasic response, with restoration of MMP-2 levels and localization. These results indicate that chronic oxygen deprivation causes an overall degeneration in tissue architecture, combined with an imbalance in proteolytic expression and a decrease in proliferative capacity. We propose that these tissue changes are representative of the ischemic condition and that our experimental model system is appropriate for addressing mechanisms of susceptibility to chronic wounds. [ABSTRACT FROM AUTHOR]

Adequate wound bed preparation is essential for healing of leg ulcers, and consists of controlling exudate and edema, decreasing the bacterial burden, promoting healthy granulation tissue, and removing necrotic tissue. Currently, there is no classification system for wound bed preparation that has predictive value. Based on past work and the authors’ experience, we have now developed and tested a new classification system that scores the following parameters: healing edges (wound edge effect), presence of eschar, greatest wound depth/granulation tissue, amount of exudate amount, edema, peri-wound dermatitis, peri-wound callus and or fibrosis, and a pink/red wound bed. Each parameter receives a score from 0 (worst score) to 2 (best score), and all the parameter scores are added for a total score. Each wound can have a maximum score of 16 (the best score possible), to a minimum score of 0 (the worst score possible). We used this wound bed score (WBS) system in a study of 177 patients with venous ulcers who had been prospectively treated with and randomized to either conventional therapy (compression alone) or a living bilayered skin construct (BSC). We evaluated serial photographs at baseline to determine whether the results would be predictive of complete wound closure and could validate the WBS. We found that wounds that ultimately achieved full closure had a statistically significant higher WBS than those that did not heal ( p = 0.0012). This was also true when separating wounds by treatment modality: standard therapy ( p = 0.044) and treatment with a BSC ( p = 0.011). When dividing the WBS in the following quartile groups: scores 4–10, 10–12, 12–13, and 13–16, the percentage of healed wounds correlated with the WBS ( p = 0.0008). For all wounds, a one unit increase in total WBS resulted on average in a 22.8% increase in odds of healing (OR = 1.228). This WBS seems to have validity in predicting complete wound closure in wounds treated with either standard therapy or advanced modalities, such as BSC. If confirmed and widely adopted in this and other types of wounds, it could be a useful tool in both the clinical and research setting. [ABSTRACT FROM AUTHOR]

Dermo-epidermal equivalents based on plasma-derived fibrin hydrogels have been extensively studied for skin engineering. However, they showed rapid degradation and contraction over time and low mechanical properties which limit their reproducibility and lifespan. In order to achieve better mechanical properties, elasticity and biological properties, we incorporated a elastin-like recombinamer (ELR) network, based on two types of ELR, one modified with azide (SKS-N3) and other with cyclooctyne (SKS-Cyclo) chemical groups at molar ratio 1:1 at three different SKS (serine-lysine-serine sequence) concentrations (1, 3, and 5 wt.%), into plasma-derived fibrin hydrogels. Our results showed a decrease in gelation time and contraction, both in the absence and presence of the encapsulated human primary fibroblasts (hFBs), higher mechanical properties and increase in elasticity when SKSs content is equal or higher than 3%. However, hFBs proliferation showed an improvement when the lowest SKS content (1 wt.%) was used but started decreasing when increasing SKS concentration at day 14 with respect to the plasma control. Proliferation of human primary keratinocytes (hKCs) seeded on top of the hybrid-plasma hydrogels containing 1 and 3% of SKS showed no differences to plasma control and an increase in hKCs proliferation was observed for hybrid-plasma hydrogels containing 5 wt.% of SKS. These promising results showed the need to achieve a balance between the reduced contraction, the better mechanical properties and biological properties and indicate the potential of using this type of hydrogel as a testing platform for pharmaceutical products and cosmetics, and future work will elucidate their potential. [ABSTRACT FROM AUTHOR]

Significance: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known. Aim: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed. Approach: Optical and biomechanical properties of these artificial human skin substitutes were investigated using the inverse adding-doubling method and tensile tests, respectively. Results: The analysis of the optical properties revealed that the model that most resembled the optical behavior of the native human skin in terms of absorption and scattering properties was the dermoepidermal human skin substitutes after 7 to 14 days in culture. The time-course evaluation of the biomechanical parameters showed that the dermoepidermal substitutes displayed significant higher values than acellular and dermal skin substitutes for all parameters analyzed and did not differ from the control skin for traction deformation, stress, and strain at fracture break. Conclusions: We demonstrate the crucial role of the cells from a physical point of view, confirming that a bioengineered dermoepidermal human skin substitute based on fibrin-agarose biomaterials is able to fulfill the minimal requirements for skin transplants for future clinical use at early stages of in vitro development. [ABSTRACT FROM AUTHOR]

Clinical use of bioengineered skin in reconstructive surgery has been established for more than 30 years. The limitations and ethical considerations regarding the use of animal models have expanded the application of bioengineered skin in the areas of disease modeling and drug screening. These skin models should represent the anatomical and physiological traits of native skin for the efficient replication of normal and pathological skin conditions. In addition, reliability of such models is essential for the conduction of faithful, rapid, and large-scale studies. Therefore, research efforts are focused on automated fabrication methods to replace the traditional manual approaches. This report presents an overview of the skin models applicable to skin disease modeling along with their fabrication methods, and discusses the potential of the currently available options to conform and satisfy the demands for disease modeling and drug screening. [ABSTRACT FROM AUTHOR]

Progress in understanding and treating metastatic melanoma is the result of decades of basic and translational research as well as the development of better in vitro tools for modeling the disease. Here, we review the latest therapeutic options for metastatic melanoma and the known genetic and non-genetic mechanisms of resistance to these therapies, as well as the in vitro toolbox that has provided the greatest insights into melanoma progression. These include next-generation sequencing technologies and more complex 2D and 3D cell culture models to functionally test the data generated by genomics approaches. The combination of hypothesis generating and hypothesis testing paradigms reviewed here will be the foundation for the next phase of metastatic melanoma therapies in the coming years.

The aim of the study was an objective in vivo assessment of skin properties after reconstruction with two artificial dermal substitutes, Integra® and Hyalomatrix®. Twenty-seven patients underwent reconstruction of 36 skin-loss sites with full-thickness skin graft, split-thickness skin graft, Hyalomatrix® bioengineered skin substitute and sequential split-thickness skin graft and Integra® bioengineered skin substitute and sequential split-thickness skin graft. Objective assessments were carried out using three instrumental devices: Multi Probe Adapter System MPA; 22 MHz ultrasound skin scan; and Primos Pico for a three-dimensional (3D) skin scan. The skin parameters under study in our sample were: corneometry, transepidermal water loss, elastometry, colorimetry, skin thickness and 3D skin surface pattern. A skin reconstruction with Hyalomatrix seemed to most closely approach the hydration, transepidermal water loss and skin surface 3D pattern of normal skin. A skin reconstruction with Integra seemed to demonstrate the best skin colour feature and elastic properties. Although no statistically significant differences were observed, the descriptive analysis of the outcomes might suggest a better cell regulation, regenerated extracellular matrix and neoangiogenesis with the use of Hyalomatrix, and the formation of a more elastic regenerated dermis, with overall better physical, mechanical and optical properties, with the use of Integra., (© 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.)