Skin Extracellular Matrix Research Articles

Effect of cosmetic films with ascorbic acid and hyaluronic acid on transepidermal water loss

Cosmetic films are structures made of a polymer capable of forming a continuous matrix. Collagen and hyaluronic acid (HA) are components of the skin extracellular matrix and act to maintain its elasticity and resistance. Ascorbic acid (AA) acts in the formation of collagen fibers, contributing to the maintenance of their firmness and elasticity. This study aimed to evaluate the moisturizing properties of cosmetic films with AA or HA in their composition. It was also investigated whether the presence of caprylyl glycol would interfere with the TWEL of the formulations. The occlusive properties of the films were assessed based on the reduction of transepidermal water loss (TEWL) in 20 healthy participants using a Tewameter probe. At T30, 30 minutes after application, all formulations showed a reduction in TEWL compared to the control. In general, the formulations that included caprylyl glycol presented the best TEWL results after 30 min of application. However, after 60 minutes, the transepidermal water loss began to return to its basal levels. This study showed a significant difference in the TEWL value, suggesting that the topical application of the films can contribute to the improvement and maintenance of skin hydration. Keywords: cosmetic films; collagen; hyaluronic acid; ascorbic acid; skin barrier

Time-Resolved Extracellular Matrix Atlas of the Developing Human Skin Dermis.

Skin aging is a physiological issue that is still relatively poorly understood. Studies have demonstrated that the dermal extracellular matrix (ECM) plays important roles in skin aging. However, the roles of the changes in ECM characteristics and the molecules that are secreted to the extracellular space and are involved in the formation of the dermal matrix from birth to old age remain unclear. To explore the way in which the ECM microenvironment supports the functions of skin development across different age groups is also poorly understood, we used a decellularization method and matrisome analysis to compare the composition, expression, and function of the dermal ECM in toddler, teenager, adult, and elderly skin. We found that the collagens, glycoproteins, proteoglycans, and regulatory factors that support skin development and interact with these core ECM proteins were differentially expressed at different ages. ECM expression markers occurring during the process of skin development were identified. In addition, our results elucidated the characteristics of ECM synthesis, response to skin development, and the features of the ECM that support epidermal stem cell growth via the basement membrane during skin aging.

The Beneficial Effect of Rosmarinic Acid on Benzophenone-3-Induced Alterations in Human Skin Fibroblasts.

Benzophenone-3 (BP-3) is one of the most widely used chemical sunscreens. The results of many in vitro and in vivo tests confirm its high percutaneous penetration and systemic absorption, which question the safety of its wide use. The aim of our research was to assess the effect of this compound on components of the skin extracellular matrix, and to investigate whether rosmarinic acid (RA) could reduce BP-3-induced changes in human skin fibroblasts. BP-3 used at concentrations of 0.1–100 µM caused a number of unfavorable changes in the level of type I collagen, decorin, sulfated glycosaminoglycans, hyaluronic acid, elastin, and expression or activity of matrix metalloproteinases (MMP-1, MMP-2), elastase and hyaluronidase. Moreover, the intracellular retention of collagen was accompanied by changes in the expression of proteins modifying and controlling the synthesis and secretion of this protein. Most importantly, RA at a concentration of 100 µM significantly reduced or completely abolished the adverse effects of BP-3. Based on these findings, it can be concluded that this polyphenol may provide effective protection against BP-3-induced disturbances in skin cells, which may have important clinical implications.

Comparison of extracellular matrix enrichment protocols for the improved characterization of the skin matrisome by mass spectrometry

A striking feature of skin organization is that the extracellular matrix (ECM) occupies a larger volume than the cells. Skin ECM also directly contributes to aging and most cutaneous diseases. In recent years, specific ECM enrichment protocols combined with in silico approaches allowed the proteomic description of the matrisome of various organs and tumor samples. Nevertheless, the skin matrisome remains under-studied and protocols allowing the efficient recovery of the diverse ECM found in skin are still to be described. Here, we compared four protocols allowing the enrichment of ECM proteins from adult mouse back skin and found that all protocols led to a significant enrichment (up to 65%) of matrisome proteins when compared to total skin lysates. The protocols based on decellularization and solubility profiling gave the best results in terms of numbers of proteins identified and confirmed that skin matrisome proteins exhibit very diverse solubility and abundance profiles. We also report the first description of the skin matrisome of healthy adult mice that includes 236 proteins comprising 95 core matrisome proteins and 141 associated matrisome proteins. These results provide a reliable basis for future characterizations of skin ECM proteins and their dysregulations in disease-specific contexts. SignificanceExtracellular matrix proteins are key players in skin physiopathology and have been involved in several diseases such as genetic disorders, wound healing defects, scleroderma and skin carcinoma. However, skin ECM proteins are numerous, diverse and challenging to analyze by mass spectrometry due to the multiplicity of their post-translational modifications and to the heterogeneity of their solubility profiles. Here, we performed the thorough evaluation of four ECM enrichment protocols compatible with the proteomic analysis of mouse back skin and provide the first description of the adult mouse skin matrisome in homeostasis conditions. Our work will greatly facilitate the future characterization of skin ECM alterations in preclinical mouse models and will inspire new optimizations to analyze the skin matrisome of other species and of human clinical samples.

Bio-P-06 - Toll-like receptor 4 activity promotes immunosuppression in the cutaneous T-cell lymphoma microenvironment

How microenvironmental factors such as skin extracellular matrix (ECM) and resident immune cells contribute to cutaneous T-cell lymphoma (CTCL) is not well understood. Here we report a ligand-receptor interaction connecting the ECM and immunosuppressive macrophages in the CTCL microenvironment. We find that expression of a fibronectin splice variant encoding extra domain A (EDA), a hallmark of ECM dysregulation in cancer, occurs in human CTCL lesions and in mouse CTCL tumors. Notably, EDA is a ligand for toll-like receptor 4 (TLR4), a pattern recognition receptor with roles in regulating immunity within tumor microenvironments. We find that CD206+ immunosuppressive macrophages within the lesional skin of CTCL patients express high levels of TLR4. Similarly, tumor-localized CD206+ macrophages are TLR4-high in our immune-competent CTCL mouse model. Lastly, we observe the abrogation of CTCL tumor growth in TLR4 deficient mice compared to wild type. Together, these data suggest that TLR4 activity in the CTCL microenvironment promotes tumor growth, and EDA-TLR4 interactions may drive immunosuppressive macrophages. Our results uncover a link between the extracellular matrix and anti-tumor immune response that may reveal new therapeutic targets in CTCL. How microenvironmental factors such as skin extracellular matrix (ECM) and resident immune cells contribute to cutaneous T-cell lymphoma (CTCL) is not well understood. Here we report a ligand-receptor interaction connecting the ECM and immunosuppressive macrophages in the CTCL microenvironment. We find that expression of a fibronectin splice variant encoding extra domain A (EDA), a hallmark of ECM dysregulation in cancer, occurs in human CTCL lesions and in mouse CTCL tumors. Notably, EDA is a ligand for toll-like receptor 4 (TLR4), a pattern recognition receptor with roles in regulating immunity within tumor microenvironments. We find that CD206+ immunosuppressive macrophages within the lesional skin of CTCL patients express high levels of TLR4. Similarly, tumor-localized CD206+ macrophages are TLR4-high in our immune-competent CTCL mouse model. Lastly, we observe the abrogation of CTCL tumor growth in TLR4 deficient mice compared to wild type. Together, these data suggest that TLR4 activity in the CTCL microenvironment promotes tumor growth, and EDA-TLR4 interactions may drive immunosuppressive macrophages. Our results uncover a link between the extracellular matrix and anti-tumor immune response that may reveal new therapeutic targets in CTCL.

Bacterial Cellulose as a Potential Bio-Scaffold for Effective Re-Epithelialization Therapy.

Currently, there are several therapeutic approaches available for wound injury management. However, a better understanding of the underlying mechanisms of how biomaterials affect cell behavior is needed to develop potential repair strategies. Bacterial cellulose (BC) is a bacteria-produced biopolymer with several advantageous qualities for skin tissue engineering. The aim here was to investigate BC-based scaffold on epithelial regeneration and wound healing by examining its effects on the expression of scavenger receptor-A (SR-A) and underlying macrophage behavior. Full-thickness skin wounds were generated on Sprague-Dawley rats and the healing of these wounds, with and without BC scaffolds, was examined over 14 days using Masson’s trichome staining. BC scaffolds displayed excellent in vitro biocompatibility, maintained the stemness function of cells and promoted keratinocyte differentiation of cells, which are vital in maintaining and restoring the injured epidermis. BC scaffolds also exhibited positive in vivo effects on the wound microenvironment, including improved skin extracellular matrix deposition and controlled excessive inflammation by reduction of SR-A expression. Furthermore, BC scaffold significantly enhanced epithelialization by stimulating the balance of M1/M2 macrophage re-programming for beneficial tissue repair relative to that of collagen material. These findings suggest that BC-based materials are promising products for skin injury repair.

Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing.

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure. This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix. To this aim, the co-assembly behaviour of a carboxylated variant of xyloglucan (CXG) with a peptide amphiphile (PA-H3) has been investigated to generate hierarchical constructs with tuneable molecular composition, structure, and properties. Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks. At a higher concentration, CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by small-amplitude oscillatory shear rheological measurements and compression tests at different CXG/PA-H3 ratios. A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.

27379 High resolution, dynamic imaging of collagen in skin cells using a bright reporter molecule

Collagen is the main component of the skin extracellular matrix and plays an integral role in supporting and maintaining the structure and biomechanical properties of the skin. There is increased interest to understand how collagen quality is controlled by the skin’s fibroblast cells, particularly in aging, and to quantify how product formulations improve the appearance of aging skin. In this work, we have developed a new in vitro tool to visualize collagen in skin fibroblasts at high speed and high resolution using live cell imaging and super resolution microscopy.

Arecanut-induced fibrosis display dual phases of reorganising glycans and amides in skin extracellular matrix

The habit of chewing arecanut leads to fibrosis in the oral tissues, which can lead to cancer. Despite high mortality, fibrosis has limited clinical success owing to organ-specific variations, genetic predispositions, and slow progression. Fibrosis is a progressive condition that is unresponsive to medications in the severe phase. To understand underlying macromolecular changes we studied the extracellular matrix's (ECM) key molecular modifications in the early and late phase of arecanut-induced fibrosis in skin. To study the fibrosis, we topically applied arecanut extract on the mice skin. We observed that the matrix changes observe early and late phases based on ECM characteristics including the matrix proteins and the glycans. A spike in the levels of proteoglycans and β-sheet structures are noted in the early phase. A significant drop in the proteoglycans and strengthening of amide covalent interactions is observed in the late phase. Although, almost no physical changes are noticeable only in the early phase; the late phase observes thick collagen bundling and a 4-fold stiffening of the skin tissue. The study indicates that the temporal interplay of proteins and glycans determine the matrix's severity state while opening avenues to research directed towards the phase-specific clinical discovery.

Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome

Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are microfibril-associated proteins essential for anchoring TGFβ in the extracellular matrix (ECM) as well as for correct assembly of ECM components. Variants in LTBP2, LTBP3, and LTBP4 have been identified in several autosomal recessive Mendelian disorders with skeletal abnormalities with or without impaired development of elastin-rich tissues. Thus far, the human phenotype associated with LTBP1 deficiency has remained enigmatic. In this study, we report homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families. Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly). Invitro studies on proband-derived dermal fibroblasts indicate distinct molecular mechanisms depending on the position of the variant in LTBP1. C-terminal variants lead to an altered LTBP1 loosely anchored in the microfibrillar network and cause increased ECM deposition in cultured fibroblasts associated with excessive TGFβ growth factor activation and signaling. In contrast, N-terminal truncation results in a loss of LTBP1 that does not alter TGFβ levels or ECM assembly. Invivo validation with two independent zebrafish lines carrying mutations in ltbp1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. In addition, one of the mutant zebrafish lines shows voluminous and hypo-mineralized vertebrae. Overall, our findings in humans and zebrafish show that LTBP1 function is crucial for skin and bone ECM assembly and homeostasis.

060 Toll-like receptor 4 activity in the tumor microenvironment promotes cutaneous T-cell lymphoma

How microenvironmental factors such as skin extracellular matrix (ECM) and resident immune cells contribute to cutaneous T-cell lymphoma (CTCL) is not well understood. Here we report a ligand-receptor interaction connecting the ECM and immunosuppressive macrophages in the CTCL microenvironment. We find that expression of a fibronectin splice variant encoding extra domain A (EDA), a hallmark of ECM dysregulation in cancer, occurs in mouse CTCL tumors, and we confirm this finding in human CTCL lesions. Notably, EDA is a ligand for toll-like receptor 4 (TLR4), a pattern recognition receptor with roles in regulating immunity within tumor microenvironments. We find that CD206+ immunosuppressive macrophages within the lesional skin of CTCL patients express high levels of TLR4. Similarly, tumor-localized CD206+ macrophages are TLR4-high in our immune-competent CTCL mouse model. Lastly, we observe the abrogation of CTCL tumor growth in TLR4 deficient mice compared to wild-type. Together, these data suggest that TLR4 activity in the CTCL microenvironment promotes tumor growth, and EDA-TLR4 interactions may drive immunosuppressive macrophages. Our results uncover a link between the extracellular matrix and anti-tumor immune response that may reveal new therapeutic targets in CTCL.

Current Review on Polymeric Hydrogel Based

Skin tissue defects have become one of the major sources of mortality and morbidity among all age group people worldwide. Skin tissue engineering has enticed considerable heedfulness from researchers as an optimistic approach for repairing partial/ full thickness burn tissue. Skin is a highly vascularized, bio mineralized composite material composed of fibroblasts and collagen surrounded by specialized extracellular matrix with high mechanical strength and structural complexity. Although the auto grafts and allografts were regarded as the high attainment for wound repair, the approach was limited due to their inability revascularize and mimicking the damaged tissue. Further, the Polymeric hydrogels are very attractive skin tissue engineering scaffolds. The structural similarity of the polymeric hydrogels to the skin extracellular matrix provides additional benefits for non-invasive tissue repair. Owing to their poor healing ability, tissue regeneration was found to be challenging in skin tissue defects. However due to its excellent moisture retaining capabilities, biocompatibility and biodegradability several researchers shown considerable interest in potential applications of the hydrogels for skin tissue repair.Furthermore, recent progress involves the development of hydrogels with ideal mechanical and fast stimulus responsive characteristics. Moreover, hydrogels with structural similarity to the skin extracellular matrix up regulate the cell material interactions for quicker skin tissue repair and more regulated stimulus response changes in the microenvironment. This current review focused on the applications of both the synthetic and natural polymers involved in the formulation of the hydrogels for the skin tissue regeneration. Furthermore, understanding the polymers simultaneously reducing the complexity of building hydrogels should be the aim of the future research in the skin tissue regenerative medicine field.

Extracellular matrix biomimetic polymeric membranes enriched with silver nanoparticles for wound healing

Severe skin injuries, including burns, represent a real concern for the global health-care system and therefore, there is an increased interest in developing wound dressings, in order to stimulate and enhance skin tissue repair. The aim of this study was to design novel hybrid materials, biomimetic to skin extracellular matrix and enriched with silver nanoparticles (nAg), in order to provide both dermal tissue regeneration and antimicrobial activity. Two material variants (variant A and variant B) consisting of type I collagen (COL), chondroitin sulfate (CS) and k-elastin peptides (EL) enriched with positively-charged nAg, were conditioned as membranes. UV exposure ensured both sterilisation and cross-linking of the materials. Physico-chemical characterization of the hybrid biomaterials showed values of density and swelling degree higher than those of COL membrane, while the process of in vitro degradation followed a similar pattern. Infrared spectroscopy and x-ray diffraction indicated alterations of the characteristic structural features and crystallinity of COL after blending with CS and EL and nAg embedding. Scanning electron microscopy observations revealed different surface morphologies of the hybrid membranes, according to their composition. In vitro studies on L929 fibroblasts and HaCaT keratinocytes showed that both hybrid membranes exhibited good cytocompatibility and promoted higher cell proliferation compared to COL sample, as evaluated by MTT and Live/Dead assays. The presence of actin filaments highlighted by fluorescent labelling confirmed the fibroblast and keratinocyte adhesion onto the surface of hybrid membranes. Most importantly, both materials showed an increased wound healing ability in an in vitro scratch assay model, stimulating cell migration at 24 h post-seeding. In addition, good antimicrobial activity was recorded, especially against Gram-positive bacterial strain. Altogether, our findings recommend COL-CS-EL-nAg hybrid membranes as good candidates for wound healing acceleration and bioengineering of skin tissue.

Collagen based electrospun materials for skin wounds treatment.

Materials used for wound care have evolved from simple covers to functional wound dressings with bioactive properties. Electrospun nanofibers show great similarity to the natural fibrillar structure of skin extracellular matrix (ECM); therefore, by mimic, the morphology of ECM, nanofibers show high potential for facilitating the healing of skin injuries. Besides morphology, scaffold composition is another important parameter in the production of bioactive wound dressings. Collagen type I is the main structural protein of skin ECM is biocompatible, biodegradable, and its extraction from animal sources is relatively simple. The fabrication of electrospun wound dressings based on collagen and its blends have been studied for skin tissue engineering applications. This review focus on the new advances of collagen electrospun materials for skin wound treatment. It summarizes the recent research on pristine collagen, collagen blends, and collagen surface modifications on nanofibers mats. Finally, the strategies for three-dimensional nanofibers production will also be discussed.

Box‐Behnken Design a Key Tool to Achieve Optimized PCL/Gelatin Electrospun Mesh

AbstractHybrid electrospun nanofibers of polycaprolactone (PCL)/gelatin are considered as drug‐delivery systems for increasing the treatment efficacy in superficial (skin) wounds. Continuous delivery of therapeutic agents, skin extracellular matrix similarity, management of wound exudate, and antimicrobial barrier effect are the major advantages of electrospun nanofibers in skin applications. Additionally, combining the favorable properties of PCL and gelatin, regarding their biocompatibility, biodegradability and mechanical performance have been revealed promising parameters to be considered for blend in hybrid structures. However, the usual optimization protocol of nanofibers’ production in electrospinning is based on the observation of one‐variable‐at‐time being this methodology expensive and time‐consuming. Therefore, in this research work, a statistical model based on four input variables namely, the flow rate, the needle‐working distance, the applied voltage, and the ratio of PCL in the solution, is developed to predict the behavior of nanofibers. The performance of nanofibers is monitored by measurements of fiber's diameter, mesh's thickness, and mesh's permeability. Overall, the model showed to be statistically significant (p‐value < 0.05) and an independent analysis validated the predicted response for optimal condition. Finally, a delivery study is performed to evaluate the electrospun mesh performance as a drug carrier.

Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging.

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

In vivo confocal Raman spectroscopic imaging of the human skin extracellular matrix degradation due to accumulated intrinsic and extrinsic aging.

Skin aging is a dynamic process that affects the entire body, marked by molecular and structural changes. Type I collagen is the most abundant structural component and accounts 80% of total collagen in human skin. The amount of proline and hydroxyproline reflect the quantity and quality of the collagen fiber in the extracellular matrix of skin, which is alerted due to accumulated effects of intrinsic and extrinsic aging. Extrinsic aging is driven by ultraviolet radiation-induced reactive oxygen species production that activates the matrix metalloproteinase and disrupts the extracellular matrix of skin dermis, while intrinsic aging is the non-enzymatic process resulting in advanced glycation end products (AGEs). In the presence of pentosidine-AGEs, aging process is accelerated. In vivo Raman spectra of human dermis were collected from forearms of 30 volunteers and were divided into three groups: 10 young adult 25±5years, 10 old adult 65±10years and 10 diabetic old adult 65±10years old male participants. Density functional theory was performed to compute the vibration modes of AGEs, pentosidine, and glucosepane. In vivo confocal Raman spectroscopy detects the specific changes in the proline and hydroxyproline conformation, collagen fiber degradation of type I collagen and AGE protein contribution to specific Raman bands in the aged dermis because of Intrinsic and Extrinsic aging. Statistical t test marked significant differences (P<.01) in Raman peaks of proline and hydroxyproline among young adult, old adult, and diabetic old adult participants at wavenumbers 855, 875, 922, and 938cm-1 . In vivo confocal Raman spectroscopy is a useful tool to detect the AGE markers in the old adult and diabetic old adult male participants, which interacts with the ultraviolet radiations and accelerates the aging process resulting in the extracellular matrix degradation.

Enhanced Cellular Uptake and Sustained Transdermal Delivery of Collagen for Skin Regeneration

The present study reports a method for transporting high molecular weight collagen for skin regeneration. An independent engineered enzymatic vehicle that has the ability for efficient transdermal delivery of regenerative biomaterial was developed for tissue regeneration. Collagen has been well recognized as a skin regeneration molecule due to its interaction with the extracellular matrix to stimulate skin cell growth, proliferation, and differentiation. However, the transdermal delivery of collagen poses a significant challenge due to its high molecular weight as well as a lack of efficient approaches. Here, to improve the transdermal delivery efficiency, α-1,4-glycosidic hydrolase was engineered with genetically encoded 3,4-dihydroxy-L-phenylalanine, which enhanced its biological activity as revealed by microscale thermophoresis. The remodeled catalytic pocket resulted in enhanced substrate binding activity of the enzyme with a predominant glycosaminoglycan (chondroitin sulfate) present in the extracellular matrix of the skin. The engineered enzyme rapidly opened up the skin extracellular matrix fiber (15 min) to ferry collagen across the wall, without disturbing the cellular bundle architecture. Confocal microscopy indicated that macromolecules had diffused three times deeper into the engineered enzyme-treated skin than the native enzyme-treated skin. Gene expression, histopathology, and hematology analysis also supported the penetration of macromolecules. Cytotoxicity (mammalian cell culture) and in vivo (Caenorhabditis elegans and Rattus noryegicus) studies revealed that the congener enzyme could potentially be used as a penetration enhancer, which is of paramount importance for the multimillion cosmetic industries. Hence, it offers promise as a pharmaceutical enzyme for transdermal delivery bioenhancement and dermatological applications.

An Overview of Biopolymeric Electrospun Nanofibers Based on Polysaccharides for Wound Healing Management.

Currently, despite the thoroughgoing scientific research carried out in the area of wound healing management, the treatment of skin injuries, regardless of etiology remains a big provocation for health care professionals. An optimal wound dressing should be nontoxic, non-adherent, non-allergenic, should also maintain a humid medium at the wound interfacing, and be easily removed without trauma. For the development of functional and bioactive dressings, they must meet different conditions such as: The ability to remove excess exudates, to allow gaseous interchange, to behave as a barrier to microbes and to external physical or chemical aggressions, and at the same time to have the capacity of promoting the process of healing by stimulating other intricate processes such as differentiation, cell adhesion, and proliferation. Over the past several years, various types of wound dressings including hydrogels, hydrocolloids, films, foams, sponges, and micro/nanofibers have been formulated, and among them, the electrospun nanofibrous mats received an increased interest from researchers due to the numerous advantages and their intrinsic properties. The drug-embedded nanofibers are the potential candidates for wound dressing application by virtue of: Superior surface area-to volume ratio, enormous porosity (can allow oxy-permeability) or reticular nano-porosity (can inhibit the microorganisms’adhesion), structural similitude to the skin extracellular matrix, and progressive electrospinning methodology, which promotes a prolonged drug release. The reason that we chose to review the formulation of electrospun nanofibers based on polysaccharides as dressings useful in wound healing was based on the ever-growing research in this field, research that highlighted many advantages of the nanofibrillary network, but also a marked versatility in terms of numerous active substances that can be incorporated for rapid and infection-free tissue regeneration. In this review, we have extensively discussed the recent advancements performed on electrospun nanofibers (eNFs) formulation methodology as wound dressings, and we focused as well on the entrapment of different active biomolecules that have been incorporated on polysaccharides-based nanofibers, highlighting those bioagents capable of improving the healing process. In addition, in vivo tests performed to support their increased efficacy were also listed, and the advantages of the polysaccharide nanofiber-based wound dressings compared to the traditional ones were emphasized.

Potential Anti-Skin Aging Effect of (-)-Catechin Isolated from the Root Bark of Ulmus davidiana var. japonica in Tumor Necrosis Factor-α-Stimulated Normal Human Dermal Fibroblasts

Reactive oxygen species (ROS) are generated during skin aging, including intrinsic (chronologic aging) and extrinsic aging (photoaging). Therefore, antioxidants that inhibit ROS generation can delay skin aging. In this study, we evaluated the potential anti-skin aging effect of (-)-phenolic compounds isolated from the root bark of Ulmus davidiana var. japonica. We preferentially investigated the possible preventive effects of isolates against the degradation of skin extracellular matrix. Among the isolates, (-)-catechin suppressed the activity of collagenase MMP-1, and reversed the degradation of collagen induced by tumor necrosis factor-α (TNF-α) in normal human dermal fibroblast. This action mechanism of (-)-catechin was validated by the suppression of tumor necrosis factor-α-induced accumulation of ROS and activation of mitogen-activated protein kinases, protein kinase B (Akt), and cyclooxygenase-2 (COX-2). The proinflammatory cytokines upregulate inflammatory reactions, and ultimately promote aging-related reactions. In this milieu, we demonstrated that (-)-catechin decreased the expression and secretion of proinflammatory cytokines, including interleukin (IL)-1β and IL-6. In conclusion, (-)-catechin is a candidate to ameliorate both intrinsic and extrinsic skin aging.