Skin Cell Proliferation Research Articles

Preparation and characterization of an antibacterial CMC/PCL hydrogel films containing CIP/Cur: In vitro and in vivo evaluation of wound healing activity

Wound healing process significantly impeded by prolonged inflammation responses, infection at the wound site, and insufficient angiogenesis. The sustained release of anti-inflammation and anti-bacterial drugs has the potential to control immune responses, improve angiogenesis, accelerate wound healing, and re-epithelialization. In this research a multifunctional hydrogel containing carboxy methyl cellulose (CMC) and polycaprolactone (PCL), along with Ciprofloxacin (CIP) and Curcumin (Cur) was developed. Physicochemical characteristics as well a biological one such as antibacterial and drug release properties, Collagen deposition, inflammatory responses, angiogenesis, and epidermal regenerated thickness were investigated via in vitro and in vivo assay. The results revealed that the CMC/PCL-based wound dressing has the potential to provide an appropriate level of water absorption (~300 %) to absorb wound exudate and ideal WVTR in range of 2279–2363 g/m2 for wound healing application. Addition of CIP and Cur to CMC/PCL hydrogel improved the skin cell proliferation, cell migration, and antibacterial activity. It also led to superior Collagen I synthesis (~2–4 times), controlled pro-inflammatory and improved anti-inflammatory cytokine secretion of macrophages, and accelerated wound healing in comparison to CMC/PCL hydrogel. In conclusion, the engineered multifunctional hydrogel showed a potential effect for accelerating wound healing and skin regeneration.

Extraction and functional characterization of fucoidans and alginates from Ecklonia maxima: A focus on skin, immune, and intestinal health

Polysaccharides from the brown seaweed Ecklonia maxima (EM), were structurally characterized using high performance size exclusion chromatography (HPSEC), Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopy, and assessed for immunomodulation. MTT and AlamarBlue assays evaluated their effects on cell viability and proliferation (skin cells; HDF, HaCaT). Nitric oxide (NO) production and phagocytosis activities were evaluated using RAW264.7 cells. In addition, Caco-2 cells were exposed to EM polysaccharides, including fucoidans and alginates, with the aim of evaluating their potential toxicity towards intestinal cells. The expression levels of tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β1) were measured by qPCR at 24 h after treatment with fucoidans (EM-1A, EM-1B, EM-2B, EM-3B) and alginates (EM-2A, EM-3A) polysaccharide fractions, demonstrating that EM-2A and 3A effectively inhibited inflammation, while EM-2B increased wound healing in HaCaT. Skin cell proliferation and migration were significantly increased (0.13 μg/μL), while exposure of RAW264.7 cells to cold or hot-extracted (2A, 2B) polysaccharides did not affect cell proliferation within 24 h. Cell proliferation in Caco-2 cells were significantly reduced by EM-1A fraction at 72 h, inhibiting cell proliferation (p < 0.001). Phagocytosis activity was significantly higher in EM-2B (122.3 ± 1.2%, p < 0.0001), suggesting pro-inflammatory potential. HDF cell proliferation was higher in EM-3A, whereas SOD activity was lower than controls (LPS: 27.3 ± 1.3%). Fucoidan from fraction 2B fraction accelerated skin cell proliferation and migration, showing their potential as bioactive compounds. The findings suggest that EM fucoidan and alginate polysaccharides would be useful for the development of products for food, pharmaceutical and biotechnology applications.

Environmental fluoxetine promotes skin cell proliferation and wound healing

This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and personal care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and a human keratinocyte cell line, we show that exposure to environmental FLX promotes wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. Using several –omics and pharmaceutical approaches, we demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases linked to the MAPK pathway. Consistent with this, phosphoproteomic analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. Treatment of skin biopsies and keratinocytes with ketanserin, a serotonin receptor antagonist, reversed the increase in wound closure observed upon exposure. These findings collectively show that exposure to environmental FLX promotes wound healing through modulating serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results justify a transition from the study of behavioural effects of environmental FLX in aquatic animals to the investigation of effects of exposure on wound healing in aquatic and terrestrial animals, including direct impacts on human health.

Curcumin Nanogel Preparations: A Promising Alternative for Psoriasis Treatment.

Curcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of Curcuma longa, commonly known as turmeric. It has been used for centuries in traditional medicine and is gaining increasing attention in modern medicine owing to its potential therapeutic benefits. Psoriasis is a chronic inflammatory disease characterized by red scaly patches on the skin. Curcumin has been found to be effective in treating psoriasis by inhibiting the activity of various enzymes and proteins involved in the inflammation and proliferation of psoriatic skin cells. Nanogel preparation of curcumin has been found to be a promising approach for the delivery of compounds to treat psoriasis. Nanogels are composed of biocompatible and biodegradable crosslinked hydrogels. The nanogel formulation of curcumin increases its solubility, stability, and bioavailability, indicating that a lower dose is needed to achieve the same therapeutic effect. This review article suggests that the nanogel preparation of curcumin can be a better alternative for psoriasis treatment as it increases the bioavailability and stability of curcumin and also reduces the required dosage. This study suggests that curcumin nanogel preparations are promising alternatives to traditional psoriasis treatments and could potentially be used as a more effective and safe treatment option. This article highlights the need for further research to fully understand the potential of curcumin nanogel preparations for psoriasis treatment in humans.

Holistic investigation of the anti-wrinkle and repair efficacy of a facial cream enriched with C-xyloside.

To investigate the repairing and anti-wrinkle efficacy of the facial cream enriched with C-xyloside, aiming at comprehensively evaluating its skin anti- aging effect and clarify its potential mechanism of action. The repairing efficacy was studied on 3D epidermis skin model and the antiaging efficacy was studied on ex-vivo human skin. Two clinical studies were conducted with Chinese females. In the first study, 49 subjects aged between 30 and 50 with wrinkle concerns were recruited and instructed to apply the investigational cream containing C-xyloside for 8 weeks. Wrinkles attributes were assessed by dermatologist. Instrumental measurements on skin hydration, trans-epidermal water loss (TEWL), and skin elasticity were also conducted. In the second study, 30 subjects aged between 25 and 60 with self-declared sensitive skin and facial redness were recruited and instructed to apply the cream for 4 weeks. Biomarker analysis of the stratum corneum was conducted through facial tape strips. The cream improved the histomorphology of the 3D epidermis skin model after SLS stimulation, and significantly increase the expression of LOR and FLG. On human skin, the cream improved the histopathology induced by UV, and significantly increased the protein content of COL I and COL III, collagen density and the number of Ki-67 positive cell of skin compared with model group (n = 3, p < 0.01). The results from the first clinical study demonstrate a significant increased the skin hydration and elasticity by 21.90%, 13.08% (R2) and 12.30% (R5), respectively (n = 49, p < 0.05), and the TEWL values decreased by 33.94% (n = 49, p < 0.05), after 8 weeks application of the cream. In addition, the scores for nasolabial folds, glabellar wrinkle, underneath eye wrinkles, crow's feet wrinkle and forehead wrinkle in the volunteers exhibited a significant reduction of 34.02%, 43.34%, 50.03%, 33.64% and 55.81% respectively (n = 49, p < 0.05). The (rCE)/(fCE) ratio of volunteers based on tape stripping significant increased after using the sample cream (n = 30, p < 0.05). The cream containing C-xyloside showed improvement of skin wrinkles and enhancement of skin barrier function. These efficacies may be attributed to the fact that the sample cream can increase the expression of skin barrier related proteins LOR and FLG, promote the maturation of cornified envelope, enhance collagen I and III protein expression and stimulate skin cell proliferation, to provide sufficient evidence supporting its antiaging efficacy of skin.

Tetrastigma hemsleyanum polysaccharides alleviate imiquimod-induced psoriasis-like skin lesions in mice by modulating the JAK/STAT3 signaling pathway

BackgroundThe pathogenesis of psoriasis involves the interaction between keratinocytes and immune cells, leading to immune imbalance. While most current clinical treatment regimens offer rapid symptom relief, they often come with significant side effects. Tetrastigma hemsleyanum polysaccharides (THP), which are naturally nontoxic, possess remarkable immunomodulatory and anti-inflammatory properties. MethodsIn this study, we utilized an imiquimod (IMQ)-induced psoriasis mouse model and a LPS/IL-6-stimulated HaCaT model. The potential and mechanism of action of THP in psoriasis treatment were assessed through methods including Psoriasis Area Severity Index (PASI) scoring, histopathology, flow cytometry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). ResultsPercutaneous administration of THP significantly alleviated symptoms and manifestations in IMQ-induced psoriatic mice, including improvements in psoriatic skin appearance (erythema, folds, scales), histopathological changes, decreased PASI scores, and spleen index. Additionally, THP suppressed abnormal proliferation of Th17 cells and excessive proliferation and inflammation of keratinocytes. Furthermore, THP exhibited the ability to regulate the JAK/STAT3 signaling pathway. ConclusionFindings from in vivo and in vitro studies suggest that THP can inhibit abnormal cell proliferation and excessive inflammation in lesional skin, balance Th17 immune cells, and disrupt the interaction between keratinocytes and Th17 cells. This mechanism of action may involve the modulation of the JAK/STAT3 signaling pathway, offering potential implications for psoriasis treatment.

Innovative Approaches in Psoriasis Management: Integration of Novel Drug Delivery Systems, Herbal Medicine, and Lifestyle Modifications

Psoriasis, a complex inflammatory skin disorder, is characterized by rapid skin cell proliferation resulting in thick, red patches covered with silvery scales. This review explores the multidimensional approach to managing psoriasis, which encompasses current therapies such as systemic medications, topical treatments, and phototherapy, all known to have potential side effects. Recognizing the associated increased risk of comorbidities like psoriatic arthritis, anxiety, and cardiovascular diseases among others, this paper also delves into the promising role of herbal medicines which are gaining popularity due to their accessibility, cost-effectiveness, and potential efficacy. Additionally, it highlights the emerging advancements in novel drug delivery systems including liposomes, nanostructured lipid carriers, and microneedles, aimed at enhancing treatment efficacy through improved drug targeting and reduced side effects. This comprehensive review seeks to provide valuable insights for the development of safer and more effective therapeutic strategies, offering a beacon of hope for those afflicted by this chronic condition and guiding future research in the field. Keywords: Psoriasis, novel drug delivery systems, liposomes, nanostructured lipid carriers, microneedles, herbal medicine, lifestyle modifications, biologic agents

Skin lesion classification using modified deep and multi-directional invariant handcrafted features

Skin lesions encompass various skin conditions, including cancerous growths resulting from uncontrolled proliferation of skin cells. Globally, this disease affects a significant portion of the population, with millions of fatalities recorded. Over the past three decades, there has been a concerning escalation in diagnosed cases of skin cancer. Early detection is crucial for effective treatment, as late diagnosis significantly heightens mortality risk. Existing research often focuses on either handcrafted or deep features, neglecting the diverse textural and structural properties inherent in skin lesion images. Additionally, reliance on a single optimizer in CNN-based schemes poses efficiency challenges. To tackle these issues, this paper presents two novel approaches for classifying skin lesions in dermoscopic images to assess cancer severity. The first approach enhances classification accuracy by leveraging a modified VGG-16 network and employing both RMSProp and Adam optimizers. The second approach introduces a Hybrid CNN Model, integrating deep features from the modified VGG-16 network with handcrafted color and multi-directional texture features. Color features are extracted using a non-uniform cumulative probability-based histogram method, while texture features are derived from a 45∘ rotated complex wavelet filter-based dual-tree complex wavelet transform. The amalgamated features facilitate accurate prediction of skin lesion classes. Evaluation on ISIC 2017 skin cancer classification challenge images demonstrates significant performance enhancements over existing techniques.

Development of topical silver nano gel formulation of Bixin: Characterization, and evaluation of anticancer activity

ObjectiveSkin cancer refers to the pathological condition characterized by the proliferation of atypical skin cells in an uncontrolled manner. Plant-based products such as bixin although show promising anticancer properties, but maintaining their stability in a formulation is a difficult task. The objective of the research is to formulate a silver nanoparticle gel preparation of bixin and evaluate its anticancer properties. MethodsThe extract from Bixa orellana seed was prepared by hot extraction technique to isolate the active ingredient, bixin. A green synthesis approach was utilized for preparing the silver nanoparticle gel of bixin (BOAgNPs). Characterization of silver nanoparticles was done using FTIR, scanning electron microscopy, compatibility study, homogeneity testing, pH evaluation, and drug content determination. The in-vitro anticancer activity was performed using cell lines (B16F10) and in-vivo by chemical carcinogen (7,12-dimethylbenz (a) anthracene) in mice. ResultsThe BOAgNPs-loaded topical gel was found to be homogeneous (clear orange color) and pH-compatible (pH ≈ 6.66) with the skin. The characterization studies indicated the presence of all functional groups in the formulation. An optimized batch of bixin-nano gel showed about 60% inhibitory effects on B16F10 cell lines (in-vitro activity) when equated with a reference drug, 5-fluorouracil. The in-vivo anticancer study suggested suppression of tumorigenesis and promotion of the healing process with bixin-nano gel application on the skin. ConclusionThe results suggested the promising anticancer property of bixin when formulated in silver nanoparticle gel. The preparation of silver particles nano gel with bixin might provide an effective alternative option for treating skin cancers, provided more research complements the findings of the present study.

Automated Prediction of Malignant Melanoma using Two-Stage Convolutional Neural Network.

A skin lesion refers to an area of the skin that exhibits anomalous growth or distinctive visual characteristics compared to the surrounding skin. Benign skin lesions are noncancerous and generally pose no threat. These irregular skin growths can vary in appearance. On the other hand, malignant skin lesions correspond to skin cancer, which happens to be the most prevalent form of cancer in the United States. Skin cancer involves the unusual proliferation of skin cells anywhere on the body. The conventional method for detecting skin cancer is relatively more painful. This work involves the automated prediction of skin cancer and its types using two stage Convolutional Neural Network (CNN). The first stage of CNN extracts low level features and second stage extracts high level features. Feature selection is done using these two CNN and ABCD (Asymmetry, Border irregularity, Colour variation, and Diameter) technique. The features extracted from the two CNNs are fused with ABCD features and fed into classifiers for the final prediction. The classifiers employed in this work include ensemble learning methods such as gradient boosting and XG boost, as well as machine learning classifiers like decision trees and logistic regression. This methodology is evaluated using the International Skin Imaging Collaboration (ISIC) 2018 and 2019 dataset. As a result, the first stage CNN which is used for creation of new dataset achieved an accuracy of 97.92%. Second stage CNN which is used for feature selection achieved an accuracy of 98.86%. Classification results are obtained for both with and without fusion of features. Therefore, two stage prediction model achieved better results with feature fusion.

Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-α, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-β, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (∼93%) was significantly greater than the control group (∼58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.

Multiomics Analysis Unravels Alteration in Molecule and Pathways Involved in Nondiabetic Chronic Wounds.

The prevalence of chronic wounds (CW) continues to grow. A thorough knowledge of the mechanism of CW formation remains elusive due to a lack of relevant studies. Furthermore, most previous studies concentrated on diabetic ulcers with relatively few investigations on other types. We performed this multiomics study to investigate the proteomic and metabolomic changes in wound and surrounding tissue from a cohort containing 13 patients with nondiabetic CW. Differentially expressed proteins (DEPs) and metabolites (DEMs) were filtered out and analyzed through multiomic profiling. The DEPs were further confirmed with the use of parallel reaction monitoring. Compared with the surrounding tissue, there were 82 proteins and 214 metabolites altered significantly in wound tissue. The DEPs were mainly enriched in focal adhesion (FA), extracellular matrix-receptor interaction (ERI), and the PI3K-Akt (PA) signaling pathway. Moreover, the DEMs were significantly enriched in amino sugar and nucleotide sugar metabolism and biosynthesis of nucleotide sugar pathways. In correlation analysis, we discovered that the PA signaling pathway, as well as its upstream and downstream pathways, coenriched some DEPs and DEMs. Additionally, we found that FBLN1, FBLN5, and EFEMP1 (FBLN3) proteins dramatically elevated in wound tissue and connected with the above signaling pathways. This multiomics study found that changes in FA, ERI, and PA signaling pathways had an impact on the cellular activities and functions of wound tissue cells. Additionally, increased expression of those proteins in wound tissue may inhibit vascular and skin cell proliferation and degrade the extracellular matrix, which may be one of the causes of CW formation.

A novel sprayable thermosensitive hydrogel containing a sulfobutylether-β-cyclodextrin/glabridin inclusion complex promotes wound healing

This study concentrated on developing a novel sprayable hydrogel by the combination of a thermosensitive hydrogel (Pluronic F-127, PF-127) and an inclusion complex of glabridin (GLD) and sulfobutylether-β-cyclodextrin (SBE-β-CD). GLD was encapsulated into SBE-β-CD by the freeze-drying method. The successful encapsulation of the inclusion complex was verified by Fourier transform infrared (FT-IR), X-ray diffractometer (XRD), scanning electron microscope (SEM), and nuclear magnetic resonance spectroscopy (NMR). The prepared GLD/SBE-β-CD inclusion complex exhibited 93.24%～96.46% encapsulation efficiency and 11.24%～11.93% loading capacity, and GLD/SBE-β-CD showed excellent biocompatibility on human vascular endothelial cells (HUVECs) and erythrocytes. GLD/SBE-β-CD inclusion complex exerts higher antioxidant and antibacterial activity than GLD alone. The GLD/SBE-β-CD inclusion complex was well dispersed within 20% PF-127 solution to form the PF-127/GLD/SBE-β-CD hydrogel. Introducing the inclusion complex into the PF-127 hydrogel did not influence its loose and porous structure, while PF-127/GLD/SBE-β-CD hydrogel demonstrated controlled GLD release in a sustained manner. The full-thickness skin wound model showed that the PF-127/GLD/SBE-β-CD hydrogel accelerated the healing of traumatic skin defects. In one aspect, the porous and biocompatible structure of the hydrogel provides favorable conditions for skin cell adhesion and proliferation. In another respect, GLD in therapeutic hydrogel markedly promotes the angiogenesis of endothelial cells, and the migration of keratinocytes. It also presents excellent antibacterial properties in wound surface. Taken together, this work established a novel sprayable hydrogel (PF-127/GLD/SBE-β-CD) and proved that it is an effective strategy for traumatic wound healing.

Modulation of macrophages by a phillyrin-loaded thermosensitive hydrogel promotes skin wound healing in mice

BackgroundImpaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. MethodsFirstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. ResultsPH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. ConclusionsOur study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.

Preparation and characterization of carboxymethyl cellulose/polyethylene glycol films containing bromelain/curcumin: In vitro evaluation of wound healing activity

AbstractIn this study, a wound‐healing membrane was fabricated based on carboxymethyl cellulose (CMC) and polyethylene glycol (PEG) containing curcumin (Cur) and bromelain (Br). Citric acid (CA) was used as a cross‐linking agent. This membrane showed an ideal degree of swelling, which was significantly dependent on the concentration and duration of cross‐linked CA. The chemical characterization showed the CA cross‐linker mechanism was more associated with chemical reactions with CMC carboxyl groups, and PEG hydroxyl groups played an important role in forming a hybrid polymer network. It greatly enhanced mechanical and adhesive properties, so the stress strength was improved from 29.4 to 38.52 Mpa. The hydrophilicity of the membrane surface according to the water contact angle assay showed the membrane surface is suitable for adhesion, growth, migration, and proliferation of skin cells. The drug delivery assay demonstrated that the Br and Cur were released during 48 h, but the Br followed the burst release in comparison with Cur. Antibacterial properties showed that CMC/PEG‐Cur/Br have ideal antibacterial properties for preventing the growth of bacteria. In summary, the engineered CMC/PEG containing Cur/Br films with desired cell viability properties and antibacterial activity can potentially improve and accelerate skin regeneration for chronic wound healing.Highlights Hydrogel film was prepared based on carboxymethyl cellulose (CMC), polyethylene glycol (PEG), and citric acid as cross‐linking agent. CMC/PEG film were induced controlling curcumin (Cur) and bromelain (Br) release for wound healing process. CMC/PEG film revealed a wide range of physiochemical, mechanical, adhesion, and biological properties behavior. Incorporation of Cur and Br promoted in vitro biocompatibility, L‐929 cells attachments, and cell migration.

Oat β-glucan repairs the epidermal barrier by upregulating the levels of epidermal differentiation, cell-cell junctions and lipids via Dectin-1.

Oat β-glucan could ameliorate epidermal hyperplasia and accelerate epidermal barrier repair. Dectin-1 is one of the receptors of β-glucan and many biological functions of β-glucan are mediated by Dectin-1. Dectin-1 promotes wound healing through regulating the proliferation and migration of skin cells. Thus, this study aimed to investigate the role of oat β-glucan and Dectin-1 in epidermal barrier repair. To investigate the role of Dectin-1 in the epidermal barrier, indicators associated with the recovery of a damaged epidermal barrier, including histopathological changes, keratinization, proliferation, apoptosis, differentiation, cell-cell junctions and lipid content were compared between WT and Dectin-1-/- mice. Further, the effect of oat β-glucan on the disruption of the epidermal barrier was also compared between WT and Dectin-1-/- mice. Dectin-1 deficiency resulted in delayed recovery and marked keratinization, as well as abnormal levels of keratinocyte differentiation, cell-cell junctions and lipid synthesis during the restoration of the epidermal barrier. Oat β-glucan significantly reduces epidermal hyperplasia, promotes epidermal differentiation, increases cell-cell junction expression, promotes lipid synthesis and ultimately accelerates the recovery of damaged epidermal barriers via Dectin-1. Oat β-glucan could promote CaS receptor expression and activate the PPAR-γ signalling pathway via Dectin-1. Oat β-glucan promote the recovery of damaged epidermal barriers through promoting epidermal differentiation, increasing the expression of cell-cell junctions and lipid synthesis through Dectin-1. Dectin-1 deficiency delay the recovery of epidermal barriers, which indicated that Dectin-1 may be a potential target in epidermal barrier repair.

Co-release of nitric oxide and L-arginine from poly (β-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (β-amino ester) (PβAE). In this regard, PβAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PβAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4–1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PβAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3–4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5–2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PβAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

Human Serum Albumin/Selenium Complex Nanoparticles Protect the Skin from Photoaging Injury.

Photoaging-induced skin damage leads to appearance issues and dermatoma. Selenium nanoparticles (SeNPs) possess high antioxidant properties but are prone to inactivation. In this study, human serum albumin/SeNPs (HSA-SeNPs) were synthesized for enhanced stability. HSA-SeNPs were prepared by self-assembling denatured human serum albumin and inorganic selenite. The cytotoxicity of HSA-SeNPs was assessed using the MTT method. Cell survival and proliferation rates were tested to observe the protective effect of HSA-SeNPs on human skin keratinocytes against photoaging. Simultaneously, ICR mice were used for animal experiments. H&E and Masson trichromatic staining were employed to observe morphological changes in skin structure and collagen fiber disorders after UVB irradiation. Quantitative RT-PCR was utilized to measure changes in mRNA expression levels of factors related to collagen metabolism, inflammation, oxidative stress regulation, and senescence markers. The HSA-SeNPs group exhibited significantly higher survival and proliferation rates of UVB-irradiated keratinocytes than the control group. Following UVB irradiation, the back skin of ICR mice displayed severe sunburn with disrupted collagen fibers. However, HSA-SeNPs demonstrated superior efficacy in alleviating these symptoms compared to SeNPs alone. In a UVB-irradiated mice model, mRNA expression of collagen type I and III was dysregulated while MMP1, inflammatory factors, and p21 mRNA expression were upregulated; concurrently Nrf2 and Gpx1 mRNA expression were downregulated. In contrast, HSA-SeNPs maintained the mRNA expression of those factors to be stable In addition, the level of SOD decreased, and MDA elevated significantly in the skin after UVB irradiation, but no significant differences in SOD and MDA levels between the HSA-SeNPs group with UVB irradiation and the UVB-free untreated group. HSA-SeNPs have more anti-photoaging effects on the skin than SeNPs, including the protective effects on skin cell proliferation, cell survival, and structure under photoaging conditions. HSA-SeNPs can be used to protect skin from photoaging and repair skin injury caused by UVB exposure.

A recombinant signalling-selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models.

Various preclinical and clinical studies have demonstrated the robust wound healing capacity of the natural anticoagulant activated protein C (APC). A bioengineered APC variant designated 3K3A-APC retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. This study was aimed to provide preclinical evidence that 3K3A-APC is efficacious and safe as a wound healing agent. 3K3A-APC, like wild-type APC, demonstrated positive effects on proliferation of human skin cells (keratinocytes, endothelial cells and fibroblasts). Similarly it also increased matrix metollaproteinase-2 activation in keratinocytes and fibroblasts. Topical 3K3A-APC treatment at 10 or 30 μg both accelerated mouse wound healing when culled on Day 11. And at 10 μg, it was superior to APC and had half the dermal wound gape compared to control. Further testing was conducted in excisional porcine wounds due to their congruence to human skin. Here, 3K3A-APC advanced macroscopic healing in a dose-dependent manner (100, 250 and 500 μg) when culled on Day 21. This was histologically corroborated by greater collagen maturity, suggesting more advanced remodelling. A non-interference arm of this study found no evidence that topical 3K3A-APC caused either any significant systemic side-effects or any significant leakage into the circulation. However the female pigs exhibited transient and mild local reactions after treatments in week three, which did not impact healing. Overall these preclinical studies support the hypothesis that 3K3A-APC merits future human wound studies.

Exploring the potential of an Aloe vera and honey extract loaded bi-layered nanofibrous scaffold of PCL-Col and PCL-SBMA mimicking the skin architecture for the treatment of diabetic wounds.

Diabetic wounds are often chronic in nature, and issues like elevated blood sugar, bacterial infections, oxidative stress and persistent inflammation impede the healing process. To ensure the appropriate healing of wounds, scaffolds should promote complete tissue regeneration in wounds, both functionally and structurally. However, the available scaffolds lack the explicit architecture and functionality that could match those of native skin, thus failing to carry out the scar-free skin regeneration in diabetic wounds. This study deals with the synthesis of a bi-layered nanofibrous scaffold mimicking the native skin architecture in terms of porosity and hydrophobic-hydrophilic gradients. In addition, herbal extracts of Aloe vera and litchi honey were added in consecutive layers to manage the high blood glucose level, inflammation, and increased ROS level associated with diabetic wounds. In vitro studies confirmed that the prepared scaffold with herbal extracts showed enhanced proliferation of skin cells with good mechanical strength, degradability, anti-bacterial and anti-diabetic properties. The scaffold also demonstrated superior wound healing in vivo with quicker scar-free wound recovery and appropriate skin regeneration, compared to conventional treatment. Altogether, the synthesized herbal extract loaded bi-layered nanofibrous scaffold can be used as a regenerative template for hard-to-heal diabetic wounds, offering a new strategy for the management of chronic wounds.