Highlighting the Benefits of AlpaWash in Wound Care: Case Reports in Small Animals.

Several studies have reported the potential of utilizing natural extracts in wound care, emphasizing those with anti-inflammatory and antimicrobial properties. In veterinary medicine, dermal-lesion treatment can be very challenging considering the patient's compliance and awareness of their condition. In this article, six veterinary case reports have been presented to elucidate the advantages of AlpaWash, a topical application utilized in combination with the prescribed medications of the patients, for the purpose of addressing the process of wound healing in three cats and three dogs. All animals were admitted to the veterinary clinic and treated under the supervision of a veterinarian. The cats and dogs were rescued from streets by people who lived in the neighborhood of Cão Bento´s Veterinary. They were admitted for the purpose of receiving medical care due to recent minor injuries or wounds due to a pet fight, preexisting condition, or accident. A veterinarian performed the anamnesis and monitored the animals during the period of treatment with AlpaWash. In each case report, the veterinarian observed significant improvement in the wound closures, and lesions healed within a couple of weeks to a couple of months depending on the case. The outcomes demonstrate the benefits of AlpaWash topical application and suggest that AlpaWash may be an alternative vehicle for compounded preparations in wound management.

In vitro skin retention and drug permeation study of Tongluo-Qutong rubber plaster by UPLC/UV/MS/MS

Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring.

OBJECTIVE: Demonstrate the impact of IL-10 producing T lymphocytes on mediating dermal scarring. SUMMARY BACKGROUND DATA: We demonstrated that CD4+ cells are essential to improving postinjury wound healing and preventing fibrosis. CD4+ subsets secrete differential cytokine and growth factor profiles, though their role in fibrosis is not known. IL-10, a key anti-inflammatory cytokine shown to promote regenerative wound healing, is secreted by some CD4+ subsets. We, therefore, hypothesize that IL-10 producing CD4+ T lymphocyte subsets selectively attenuate dermal wound fibrosis. METHODS: IL-10-/- and wild-type murine splenocytes were enriched for CD4+ lymphocytes and adoptively transferred into severe combined immunodeficient (SCID) mice that received full-thickness wounds which were analyzed at days 7 and 28 for inflammation and collagen content. We then sorted CD4+CD44int/lowFoxP3-CD62L+ T cells (Tnaive) or CD4+CD44HiFoxP3- type 1 regulatory (Tr1) T cell subsets from 10BiT murine splenocytes, activated them, and transferred them into wounds. In vitro, dermal fibroblasts were cocultured with Tnaive or Tr1 and the effect on extracellular matrix (ECM) regulation was analyzed. RESULTS: The anti-inflammatory and antifibrotic effects of CD4+ cells on SCID wounds were lost with cells from IL-10-/- mice. Adoptive transfer of Tr1 into SCID mice resulted in accelerated wound closure at d7 with reduced fibrosis at d28, with Tr1 favoring hyaluronan production by fibroblasts, an ECM molecule implicated in IL-10-induced regenerative healing. CONCLUSIONS: IL-10 producing T-lymphocytes, specifically Tr1, regulate inflammatory cell cytokine expression to promote HA-rich ECM deposition and attenuate fibrosis. Promoting IL-10 producing lymphocytes in wounds may be a therapeutic target to promote regenerative wound healing.

The effects of oral mucosa-derived heterotopic fibroblasts on cutaneous wound healing.

An intriguing observation that has recently found support through clinical and experimental studies is that wounds of the oral mucosa tend to display faster healing and result in less scarring than in the skin. We aimed to investigate the potential of heterotopic oral mucosal fibroblasts in cutaneous wounds while determining the main differences between wounds conditioned with either the oral mucosa or dermis-derived human fibroblasts. A total of 48 nude mice were divided into four groups: control, sham, dermal fibroblast (DF), and oral fibroblast (OF). Fibroblasts were isolated, cultured, and seeded onto fibrin scaffolds for transfer to full-thickness dorsal wounds. Cell viability, wound area, healing rate, vascularization, cellular proliferation, dermal thickness, collagen architecture, and subtypes were evaluated. Both cell groups had a viability of 95% in fibrin gel prior to transfer. None of the wounds fully epithelialized on day 10, while all were epithelialized by day 21, which resulted in scars of different sizes and quality. Healing rate and scars were similar between the control and sham groups, whereas fastest healing and least scarring were noted in the OF group. Dermal thickness was highest in the DF group, which was also supported by highest levels of collagen types I and III. Proliferative cells and vascular density were highest in the OF group. DF result in healing through a thick dermal component, while oral fibroblasts result in faster healing and less scarring through potentially privileged angiogenic and regenerative gene expression.

Protective effects of dissolved molecular hydrogen against hydrogen peroxide-, hydroperoxide-, and glyoxal-induced injuries to human skin keratinocytes.

Molecular hydrogen (H2) is recognized as a gaseous antioxidant, and it is expected to ameliorate various disorders related to oxidative stress and inflammation. However, there are still many unclear points regarding its effectiveness in the skin. Therefore, the purpose of this study was to examine the protective effect of H2 against ultraviolet (UV) irradiation-related stress injury in human epidermal HaCaT cells. We investigated the effects of H2 against three types of UV-derived oxidative stress using human skin keratinocytes: hydrogen peroxide (H2O2)-induced oxidative stress, tert-butyl hydroperoxide (t-BuOOH)-induced lipid peroxidation stress, and glyoxal-induced carbonyl stress. Our results showed that H2 exerted cytoprotective effects against stress induced by H2O2, t-BuOOH, and glyoxal. Furthermore, our results also revealed that H2 suppressed H2O2-induced increases in intracellular peroxide and H2O2 levels, and suppressed the progression of lipid peroxidation. Taken together, our results demonstrate that H2 can exert protective effects against oxidative stress-, lipid peroxidation-, and carbonyl stress-induced cellular injuries in human keratinocytes, partly mediated via suppression of intracellular oxidative stress and peroxide generation. Therefore, H2 is expected to be utilized as an effective and attractive component in cosmetic formulations in the future.

Dermal Drivers of Injury-Induced Inflammation: Contribution of Adipocytes and Fibroblasts.

Irregular inflammatory responses are a major contributor to tissue dysfunction and inefficient repair. Skin has proven to be a powerful model to study mechanisms that regulate inflammation. In particular, skin wound healing is dependent on a rapid, robust immune response and subsequent dampening of inflammatory signaling. While injury-induced inflammation has historically been attributed to keratinocytes and immune cells, a vast body of evidence supports the ability of non-immune cells to coordinate inflammation in numerous tissues and diseases. In this review, we concentrate on the active participation of tissue-resident adipocytes and fibroblasts in pro-inflammatory signaling after injury, and how altered cellular communication from these cells can contribute to irregular inflammation associated with aberrant wound healing. Furthering our understanding of how tissue-resident mesenchymal cells contribute to inflammation will likely reveal new targets that can be manipulated to regulate inflammation and repair.

In situ cellular immune response in non-ulcerated skin lesions due to Leishmania (L) infantum chagasi infection

Skin lesions of patients affected by non-ulcerated cutaneous leishmaniasis (NUCL) caused by L. (L.) infantum chagasi are characterized by lymphohistiocytic inflammatory infiltrate associated with epithelioid granuloma and scarce parasitism. However, the in situ cellular immune response of these patients is unclear. Therefore, the aim of the present study was to characterize the cellular immune response in the skin lesions of patients affected by NUCL. Methods Twenty biopsies were processed by immunohistochemistry using primary antibodies to T lymphocytes (CD4, CD8), NK cells, B lymphocytes, macrophages, nitric oxide synthase and interferon-gamma. Results Immunohistochemistry revealed higher expression of all cellular types and molecules (IFN-γ, iNOS) in the dermis of diseased skin compared to the skin of healthy individuals (p < 0.05). Morphometric analysis performed in the skin lesions sections showed the predominance of CD8+ T lymphocytes in the mononuclear infiltrate, followed by macrophages, mostly iNOS+, a response that could be mediated by IFN-γ. Conclusion Our study improves knowledge of the cellular immune response in non-ulcerated or atypical cutaneous leishmaniasis caused by L. (L.) infantum chagasi in Central America and pointed to the pivotal participation of CD8+ T lymphocytes in the host defense mechanisms against the parasite in patients with NUCL.(AU)

Effects of Pulsed 810 nm Al-Ga-As Diode Laser on Wound Healing Under Immunosuppression: A Molecular Insight.

BACKGROUND AND OBJECTIVES: Dysregulated inflammation is one of the major contributing factors for the prevalence of non-healing chronic wound in immunosuppressed subjects. Photobiomodulation (PBM) has emerged as a potential non-thermal, light-based therapeutic healing intervention for the treatment of impaired wounds. STUDY DESIGN/MATERIALS AND METHODS: The present study delineates the underlying molecular mechanisms of PBM 810 nm laser-induced full-thickness cutaneous wound repair in immunosuppressed rats at continuous and pulsed wave-mode with power-density of 40 mW/cm 2 , fluence 22.6 J/cm 2 for 10 minutes daily for 7 post-wounding days. Molecular markers were assessed using biochemical, enzyme-linked immunosorbent assay quantification, enzyme kinetics and immunoblots analyses pertaining to inflammation, oxidative stress, cell survival, calcium signaling, and proliferation cascades. RESULTS: Results distinctly revealed that pulsed 810 nm (10 Hz) PBM potentially influenced the cell survival and proliferation signaling pathway by significantly upregulated phospho-protein kinase B(phospho-Akt), phospho-extracellular-signal-regulated kinase 1 (ERK1), transient receptor potential vanilloid-3 (TRPV3), Ca2+ , calmodulin, transforming growth factor-ß1 (TGF-ß1), TGF-ßR3, and Na + /K + -ATPase pump levels. PBM treatment resulted in reduction of exaggerated inflammatory responses evident by significantly repressed levels of interleukin-1ß (IL-1ß), IL-6, cyclooxygenase 2 (COX-2), and substance-P receptor (SPR), as well as inhibited apoptotic cell death by decreasing p53, cytochrome C, and caspase 3 levels (P < 0.05), which, in turn, effectively augment the wound repair in immunosuppressed rats. PBM treatment also lowered 4-hydroxynoneal (HNE) adduct level and NADP/NADPH ratio and upregulated the GRP78 expression, which might culminate into reduced oxidative stress and maintained the redox homeostasis. CONCLUSIONS: Taken together, these findings would be helpful in better understanding of the molecular aspects involved in pulsed 810 nm laser-mediated dermal wound healing in immunosuppressed rats through regulation of cell survival and proliferation via Ca2+ -calmodulin, Akt, ERK, and redox signaling. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Alfalfa Nanofibers for Dermal Wound Healing.

Engineering bioscaffolds for improved cutaneous tissue regeneration remains a healthcare challenge because of the increasing number of patients suffering from acute and chronic wounds. To help address this problem, we propose to utilize alfalfa, an ancient medicinal plant that contains antibacterial/oxygenating chlorophylls and bioactive phytoestrogens, as a building block for regenerative wound dressings. Alfalfa carries genistein, which is a major phytoestrogen known to accelerate skin repair. The scaffolds presented herein were built from composite alfalfa and polycaprolactone (PCL) nanofibers with hydrophilic surface and mechanical stiffness that recapitulate the physiological microenvironments of skin. This composite scaffold was engineered to have aligned nanofibrous architecture to accelerate directional cell migration. As a result, alfalfa-based composite nanofibers were found to enhance the cellular proliferation of dermal fibroblasts and epidermal keratinocytes in vitro. Finally, these nanofibers exhibited reproducible regenerative functionality by promoting re-epithelialization and granulation tissue formation in both mouse and human skin, without requiring additional proteins, growth factors, or cells. Overall, these findings demonstrate the potential of alfalfa-based nanofibers as a regenerative platform toward accelerating cutaneous tissue repair.

Promotion of dermal regeneration using pullulan/gelatin porous skin substitute.

Tissue-engineered dermal substitutes represent a promising approach to improve wound healing and provide more sufficient regeneration, compared with current clinical standards on care of large wounds, early excision, and grafting of autografts. However, inadequate regenerative capacity, impaired regeneration/degradation profile, and high cost of current commercial tissue-engineered dermal regeneration templates hinder their utilization, and the development of an efficient and cost-effective tissue-engineered dermal substitute remains a challenge. Inspired from our previously reported data on a pullulan/gelatin scaffold, here we present a new generation of a porous pullulan/gelatin scaffold (PG2) served as a dermal substitute with enhanced chemical and structural characteristics. PG2 shows excellent biocompatibility (viability, migration, and proliferation), assessed by in vitro incorporation of human dermal fibroblasts in comparison with the Integra® dermal regeneration template (Control). When applied on a mouse full-thickness excisional wound, PG2 shows rapid scaffold degradation, more granulation tissue, more collagen deposition, and more cellularity in comparison with Control at 20 days post surgery. The faster degradation is likely due to the enhanced recruitment of inflammatory macrophages to the scaffold from the wound bed, and that leads to earlier maturation of granulation tissue with less myofibroblastic cells. Collectively, our data reveal PG2's characteristics as an applicable dermal substitute with excellent dermal regeneration, which may attenuate scar formation.

New lupeol esters as active substances in the treatment of skin damage.

The purpose of the research was to obtain new derivatives of natural triterpene lupeol and to evaluate their potential as active substances in the treatment of skin damage. Four new lupeol esters (propionate, succinate, isonicotinate and acetylsalicylate) and lupeol acetate were obtained using an eco-friendly synthesis method. In the esterification process, the commonly used hazardous reagents in this type of synthesis were replaced by safe ones. This unconventional, eco-friendly, method is particularly important because the compounds obtained are potentially active substances in skin care formulations. Even trace amounts of hazardous reagents can have a toxic effect on damaged or irritated tissues. The molecular structure of the esters were confirmed by 1H NMR, 13C NMR and IR spectroscopy methods. Their crystal structures were determined using XRD method. To complete the analysis of their characteristics, physicochemical properties (melting point, lipophilicity, water solubility) and biological activity of the lupeol derivatives were studied. Results of an irritant potential test, carried out on Reconstructed Human Epidermis (RHE), confirmed that the synthesized lupeol derivatives are not cytotoxic and they stimulate a process of human cell proliferation. The safety of use for tested compounds was determined in a cell viability test (cytotoxicity detection kit based on the measurement of lactate dehydrogenase activity) for keratinocytes and fibroblasts. The results obtained showed that the modification of lupeol structure improve its bioavailability and activity. All of the esters penetrate the stratum corneum and the upper layers of the dermis better than the maternal lupeol. Lupeol isonicotinate, acetate and propionate were the most effective compounds in a stimulation of the human skin cell proliferation process. This combination resulted in an increase in the concentration of cells of more than 30% in comparison to control samples. The results indicate that the chemical modification of lupeol allows to obtain promising active substances for treatment of skin damage, including thermal, chemical and radiation burns.

Macrophages significantly enhance wound healing in a vascularized skin model.

Tissue-engineered dermo-epidermal skin grafts could be applied for the treatment of large skin wounds or used as an in vitro wound-healing model. However, there is currently no skin replacement model that includes both, endothelial cells to simulate vascularization, and macrophages to regulate wound healing and tissue regeneration. Here, we describe for the first time a tissue-engineered, fully vascularized dermo-epidermal skin graft based on a fibrin hydrogel scaffold, using exclusively human primary cells. We show that endothelial cells and human dermal fibroblasts form capillary-like structures within the dermis whereas keratinocytes form the epithelial cell layer. Macrophages played a key role in controlling the number of epithelial cells and their morphology after skin injury induced with a CO2 laser. The activation of selected cell types was confirmed by mRNA analysis. Our data underline the important role of macrophages in vascularized skin models for application as in vitro wound healing models or for skin replacement therapy. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1340-1350, 2019.

High-frequency (20-MHz) high-intensity focused ultrasound (HIFU) system for dermal intervention: Preclinical evaluation in skin equivalents.

BACKGROUND: High-intensity focused ultrasound (HIFU) for non-invasive treatment of a range of internal pathologies including cancers of major organs and cerebral pathologies is in exponential growth. Systems, however, operate at relatively low frequencies, in the range of 200-2000 kHz as required for deep axial penetration of the body. HIFU utilizing frequencies in excess of 15 MHz has so far not been explored, but presents an opportunity to extend the HIFU modality to target specific dermal lesions and small animal research. MATERIALS AND METHODS: A new 20-MHz HIFU system (TOOsonix ONE-R) with narrow focus corresponding to the dermis was studied in acoustic skin equivalents, for example, in a tissue-mimicking gel and in bovine liver. HIFU lesion geometry, depth, and diameter were determined. The temperature increase in the focal point was measured as a function of acoustic power and the duration of HIFU exposure. RESULTS: The system produces highly reproducible ultrasound lesions with predictable and configurable depths of 1-2 mm, thus corresponding to the depth of the human dermis. The lesion geometry was elongated triangular and sized 0.1-0.5 mm, convergent to a focal point skin deep. Focal point temperature ranged between 40 and 90°C depending on the chosen setting. Observations were confirmed ex vivo in bovine liver and porcine muscle. Variation of acoustic power and duration of exposure produced linear effects in the range of the settings studied. Thus, effects could be adjusted within the temperature interval and spatial field relevant for clinical therapy and experimental intervention targeting the dermal layer of human skin. CONCLUSION: The tested 20-MHz HIFU system for dermal applications fulfilled key prerequisite of narrow-field HIFU dedicated to cutaneous applications regarding reproducibility, geometry, and small size of the applied ultrasound lesions. Controlled adjustment of acoustic lesions within the temperature range 40-90°C qualifies the system for a range of non-ablative and ablative applications in dermatological therapy.

Modelling optimal delivery of bFGF to chronic wounds using ODEs.

In this paper, we present an ordinary differential equation model depicting the interactions of basic fibroblast growth factor (bFGF) and its binding agents in a chronic wound. The delivery of bFGF was treated as a control variable and is coupled to an objective functional. By optimising the objective functional with respect to the control, predictions for optimal delivery rates of bFGF are proposed. The optimal control is then validated by comparing the cost of the objective functional for the optimal delivery rate and several alternative delivery rates. This paper addresses two objectives of effective drug delivery to chronic wounds. The first is to provide insight for the priority of delivering bFGF: to minimise the quantity of bFGF, or to optimise the distribution of bound bFGF. For effective concentrations of bound bFGF, the optimisation of bound bFGF must be prioritised over the minimisation of bFGF delivered. The second objective is to comment on the effect of the proteolytic environment within the wound, with the concentration of bound bFGF starting to decrease late in the treatment period for highly proteolytic environments. This will lead to long term complications with wound closure after the treatment has been completed. Also, it was found that for highly proteolytic environments, the cost of delivering bFGF increased. The need for optimal drug delivery is made apparent by the burden of chronic wounds on the medical industry across the developed world.

Interactive thermal tissue reactions of 7-MHz intense focused ultrasound and 1-MHz and 6-MHz radiofrequency on cadaveric skin.

BACKGROUND: Intense focused ultrasound (IFU) and radiofrequency (RF) systems generate thermal tissue reactions in multiple zones in the skin, with the microscopic features thereof varying according to energy sources and treatment parameters. OBJECTIVE: To evaluate interactive thermal tissue reactions of IFU and RF in cadaveric skin. METHODS: Thermal reaction patterns generated by IFU, invasive bipolar RF, and non-invasive monopolar RF treatments were analyzed in cadaveric skin of the inner thigh. Additionally, combination treatment, including IFU and invasive bipolar RF, IFU and non-invasive monopolar RF, invasive bipolar RF and IFU, and non-invasive monopolar RF and IFU, was delivered to cadaveric skin and microscopically evaluated. RESULTS: Combination treatment with 1.5-mm IFU followed by 1.5-mm invasive RF elicited multiple thermal injury zones of coagulation and ablation in the mid to lower dermis. Therein, IFU-induced thermal reactions were indistinguishable from RF-induced thermal reactions. Non-invasive RF treatment on IFU-pretreated cadaveric tissue specimens exhibited greater degrees of thermal injury, with wider and deeper penetration, compared to non-invasive RF treatment alone. Furthermore, RF-pretreated tissues showed marked differences in the patterns of IFU-induced thermal tissue reactions. CONCLUSION: Our data suggest that combination treatments with IFU and RF elicit various patterns of interactive thermal tissue reactions.

Silk fibroin produced by transgenic silkworms overexpressing the Arg-Gly-Asp motif accelerates cutaneous wound healing in mice.

We investigated the effect of silk fibroin (SF) on wound healing in mice. SF or an amorphous SF film (ASFF) prepared from silk produced by the wild-type silkworm Bombyx mori (WT-SF, WT-ASFF) or by transgenic worms that overexpress the Arg-Gly-Asp (RGD) sequence (TG-SF, TG-ASFF) was placed on 5-mm diameter full-thickness skin wounds made by biopsy punch on the back of 8-12 week-old BALB/c mice. Each wound was covered with WT-ASFF and urethane film (UF), TG-ASFF plus UF, or UF alone (control). Wound closure, histological thickness, the area of granulation tissue, and neovascularization were analyzed 4, 8, and 12 days later. The effect of SF on cell migration and proliferation was examined in vitro by scratch- and MTT-assay using human dermal fibroblasts. Wound closure was prompted by TG-ASFF, granulation tissue was thicker and larger in ASFF-treated wounds than the control, and neovascularization was promoted significantly by WT-ASFF. Both assays showed that SF induced the migration and proliferation of human dermal fibroblasts. The effects of TG-ASFF and TG-SF on wound closure, granulation formation, and cell proliferation were more profound than that of WT-ASFF and WT-SF. We document that SF accelerates cutaneous wound healing, and this effect is enhanced with TG-SF. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 97-103, 2019.

Pericytes reduce inflammation and collagen deposition in acute wounds.

BACKGROUND: Pericytes have been shown to have mesenchymal stromal cell-like properties and play a role in tissue regeneration. The goal of this study was to determine whether the addition of a pericyte sheet to a full-thickness dermal wound would enhance the healing of an acute wound. METHODS: Human muscle-derived pericytes and human dermal fibroblasts were formed into cell sheets, then applied to full-thickness excisional wounds on the dorsum of nu/nu mice. Histology was performed to evaluate epidermal and dermal reformation, inflammation and fibrosis. In addition, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine cytokine response. RESULTS: Pericytes were detected in the wounds until day 16 but not fibroblasts. Decrease in wound size was noted in pericyte sheet-treated wounds. Enhanced neo-vascularization and healthy granulation tissue formation were noted in the pericyte-treated wounds. Expression of type I collagen messenger RNA (mRNA) was significantly higher in the fibroblast-treated group, whereas Type III collagen mRNA showed significant increase in the pericyte group at days 3, 6 and 9 compared with the fibroblast and no-cell groups. Trichrome staining revealed thick unorganized collagen fibrils in the fibroblast-treated wounds, whereas pericyte-treated wounds contained thinner and more alligned collagen fibrils. Tumor necrosis factor (TNF)-α mRNA levels were increased in the fibroblast-treated wounds compared with pericyte-treated wounds. DISCUSSION: The addition of pericytes may confer beneficial effects to wound healing resulting in reduced recruitment of inflammatory cells and collagen I deposition, potential to enhance wound closure and better collagen alignment promoting stronger tissue.

Fernblock Prevents Dermal Cell Damage Induced by Visible and Infrared A Radiation.

Sun overexposure leads to higher risk of photoaging and skin cancer. The contribution of infrared (IR) and visible light (VIS) radiation is currently being taken into account in their pathogenesis. Erythema, hyperpigmentation, genotoxicity or the increase of matrix metalloproteinases (MMPs) expression are some of the effects induced by these types of radiation. Extracts of various botanicals endowed with antioxidant activity are emerging as new photoprotective compounds. A natural extract from Polypodium leucotomos (Fernblock®, FB) has antioxidant and photoprotective properties and exhibits a strong anti-aging effect. In this study, we evaluated the protective capacity of FB against the detrimental effects of infrared A (IRA) and VIS radiation in human dermal fibroblasts. We analyzed the effects of FB on the morphology, viability, cell cycle and expression of extracellular matrix components of fibroblasts subjected to VIS and IRA. Our results indicate that FB prevents cell damage caused by VIS and IRA. Moreover, it reduces the increase in MMP-1 and cathepsin K expression induced by both VIS and IRA radiation, and curbs alterations in fibrillin 1, fibrillin 2 and elastin expression. All these findings support FB as a feasible approach to prevent or treat skin damage caused by IRA or VIS exposure.

Advances in addressing full-thickness skin defects: a review of dermal and epidermal substitutes.

full-thickness skin defects remain a reconstructive challenge. Novel regenerative modalities can aid in addressing these defects. A literature review of currently available dermal and epidermal regenerates was performed. The mechanism and application for each skin substitute was analyzed to provide a guide for these modalities. Available epidermal substitutes include autografts and allografts and may be cultured or noncultured. Dermal regenerate templates exist in biologic and synthetic varieties that differ in the source animal and processing. Epidermal and dermal skin substitutes are promising adjunctive tools for addressing certain soft tissue defects and have improved outcomes in reconstructive procedures. The following article provides a comprehensive review of the biologic materials available and the types of complex wounds amenable to their use.

Skin regeneration of amphibians: A novel model for skin regeneration as adults.

Adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. Since a scar causes serious medical problems, skin regeneration, instead of formation of a scar, has been strongly desired from a clinical point of view. Recent studies have suggested multiple origins of myofibroblasts, which are scar-forming cells in skin wound healing of mammals. While amphibians have skin structures that are basically common to mammals as tetrapods, both urodele and anuran amphibians regenerate almost complete skin structures including the dermis and secretion glands without forming a remarkable scar after a deep skin injury. In skin regeneration of a metamorphosed Xenopus laevis, an amphibian, cells that resemble limb blastema cells accumulate under the epidermis after injury and cells from subcutaneous tissues (tissues underlying the skin) contribute to skin regeneration. The skin of urodele amphibians and that of anuran amphibians provide valuable models for studying skin regeneration as adults. Recent progress in transgenesis and genome editing techniques with whole genome sequencing in Xenopus and an axolotl have enabled comparative analyses by molecular genetics of mammal skin and amphibian skin. Such comparative analyses would enable direct comparison of scar-forming myofibroblasts in mammals and blastema-like cells that contribute to skin regeneration in amphibians, ultimately leading to realization of skin regeneration in adult mammals. Amphibian skin regeneration will also be useful for determining how to step up skin regeneration to a higher level of regeneration such as limb regeneration in the future.