Injured Skin Research Articles

Epidermal factor Foxn1 as a regulator of antioxidant defense in the skin

The skin, as the largest organ of the body, is constantly exposed to environmental threats, including: injuries and oxidative stress. The thioredoxin system is one of the skin antioxidant systems , which protects cells against oxidative stress, regulates cell migration, proliferation and apoptosis, and also participates in signal transmission by regulating the activity of transcription factors. Recent studies have shown a correlation between the epidermal transcription factor Foxn1 and the thioredoxin system in mouse skin. Mass spectrometry analysis, followed by in vitro and in vivo experiments, showed that Foxn1 in keratinocytes regulates elements of the electron transport chain as well as the thioredoxin system (Txn2, Txnrd3), especially under hypoxic condition. High levels of Txnrd3 mRNA were detected for the first time in the injured skin of Foxn1+/+ mice compared to Foxn1-/- mice, and also showed that Foxn1 in keratinocytes upregulates Txnrd3 protein expression. Moreover, in silico analyzes indicated possible binding sites of the transcription factor Foxn1 in the Txn system. In conclusion, the data presented in this review identify Foxn1 as a novel component of the skin antioxidant system.

Antimicrobial and wound healing potential of naphthoquinones encapsulated in nanochitosan.

Introduction: The use of chitosan in pharmaceutical formulations is an advantageous approach due to this compound intrinsic biodegradability and biocompatibility, as well as ready availability and low polymer cost. Methods: Herein, the naphthoquinones 3- chloromethylene-menadione (NQ1) and 2,3-dichloro-1,4-naphthoquinone (NQ2) were nanoencapsulated into chitosan (CNP) by the ionotropic gelatinization technique and characterized by DLS, FTIR, SEM, TGA and DSC, and their release profiles evaluated. The antimicrobial and wound healing activities were investigated. Results and Discussion: Homogeneous chitosan nanocapsulses of about 193nm and Z potential ranging from +30.6 to +33.1mV loaded with NQ1 (CNP-NQ1) or NQ2 (CNPQNQ2). With nanoencapsulation efficiencies of ≥ 96%, the solubility of naphthoquinones in aqueous environments was improved, making them suitable for biological system applications. The encapsulated naphthoquinones displayed a controlled release of approximately 80% for CNP-NQ1 and 90% for CNP-NQ2 over an 8h period at 36°C. Both CNP-NQ1 and CNP-NQ2 retained the already established free naphthoquinone antimicrobial activity against two Staphylococcus aureus strains, Staphylococcus epidermidis, Streptococcus pyogenes and Pseudomonas aeruginosa. Although presenting low toxicity to healthy human cells, only CNP-NQ1 displayed therapeutic indices above 100 for S. aureus and S. epidermidis and above 27 for S. pyogenes and P. aeruginosa, allowing for safe use in human tissues. Furthermore, CNP-NQ1 did not impair the migration of human fibroblast cells in scratch assays, adding promising wound healing properties to this formulation. These findings emphasize that CNP-NQ1 may be useful in protecting injured skin tissue from bacterial contamination, avoiding skin infections not only by reducing bacterial loads but also by accelerating the healing process until complete dermal tissue recovery.

Transdermal exposure to Chrome-III oxide resulting in intoxicaitons and morbidity in two tanning workers—a case report

Here, we report two cases of chrome-III oxide intoxications following transdermal exposure in tanning workers. A 58-year-old man (case 1) and his 41-year-old co-worker (case 2) were brought to our ED with unconsciousness six hours after accidental transdermal exposure to chrome-III oxide crystals (Tankrom® AB, Chrome-III oxide 25.5% and Schorlemmer Basicity 33%). Upon arrival, both patients presented with agitation and chemical burns affecting 11% (case 1) and 3% (case 2) of their total body surface area, respectively. Chemical burns were mainly distributed on injured skin. Initial arterial blood gas analysis revealed moderate (case 1, pH: 7.268) to mild acidosis (case 2, pH: 7.352). One of our patients (case 1) had significant respiratory depression. Laboratory results of case 1 and case 2 showed increased white blood cell counts, (16,630 mm3 and 19,950 mm3) and elevated blood glucose (178 mg/dL and 193 mg/dL), creatinine (1.33 mg/dL and 1.52 mg/dL), liver enzyme (aspartate aminotransferase/alanine aminotransferase of 416/322 U/L and 141/118 U/L) and creatine phosphokinase level (474 U/L and 566 U/L), respectively. Radiologic examinations revealed an orbital wall fracture and L2 compression fracture in case 1, while case 2 had a subdural hematoma, subarachnoid hemorrhage and scapular fracture and had to undergo an operation for external ventricular drainage. Both patients became alert on day three (case 1) and day six (case 2) and were discharged on day 27. We serially measured their serum and urinary chromium concentrations after hospital arrival. The calculated serum half-lives were 35.7 hours and 25.1 hours, and urinary half-lives were 2.3 hours and 2.5 hours in case 1 and case 2, respectively. We suggest that transdermal exposure to chrome-III oxide, especially to injured skin, may result in significant toxicity and morbidity. Therefore, it is essential to take necessary precautions and preventive measures to avoid transdermal exposure to chromium.

Raepenol™ Cream, a Complex of Natural Compounds, Promotes Wound Healing and Relieves Pruritus In Vivo.

Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.

Current and promising applications of MOF composites in the healing of diabetes wounds.

Diabetes mellitus is an exponentially growing chronic metabolic disease identified by prolonged hyperglycemia that leads to a plethora of health problems. It is well established that the skin of diabetic patients is more prone to injury, and hence, wound healing is an utmost critical restorative process for injured skin and other tissues. Diabetes patients have problems with wound healing at all stages, which ultimately results in delays in the healing process. Therefore, it is vital to find new medications or techniques to hasten the healing of wounds. Metal-organic frameworks (MOFs), an assorted class of porous hybrid materials comprising metal ions coordinated to organic ligands, can display great potential in accelerating diabetic wound healing due to their good physicochemical properties. The release of metal ions during the degradation of MOFs can promote the differentiation of fibroblasts into myofibroblasts and subsequently angiogenesis. Secondly, similar to enzyme-like active substances, they can eliminate reactive oxygen species (ROS) overproduction (secondary to the bio-load of wound bacteria), which is conducive to accelerating diabetic wound healing. Subsequently, MOFs can support the slow release of drugs (molecular or gas therapeutics) in diabetic wounds and promote wound healing by regulating pathological signaling pathways in the wound microenvironment or inhibiting the expression of inflammatory factors. In addition, the combination of photodynamic and photothermal therapies using photo-stimulated porphyrin-based MOF nanosystems has brought up a new idea for treating complicated diabetic wound microenvironments. In this review, recent advances affecting diabetic wound healing, current means of rapid diabetic wound healing, and the limitations of traditional approaches are discussed. Further, the diabetic wound healing applications of MOFs have been discussed followed by the future challenges and directions of MOF materials in diabetic wound healing.

Dynamic pathological analysis reveals a protective role against skin fibrosis for TREM2-dependent macrophages.

Rationale: Systemic sclerosis (SSc) is a chronic and incurable autoimmune disease with high mortality rates, and skin fibrosis is one of distinguishing hallmarks in the pathogenesis. However, macrophage heterogeneity regulating skin fibrosis remain largely unknown. Methods: We established mouse disease model and performed single-cell RNA-sequencing (scRNA-seq) to resolve the dynamic and heterogenous characteristics of macrophages in skin fibrosis, and the role of TREM2-dependent macrophages in the pathological process was investigated using knockout mice and intraperitoneal transferring TREM2+ macrophages combining with functional assays. Results: We show that TREM2-expressing macrophages (TREM2+ MФs) accumulate in injured skin of mice treated by bleomycin (BLM) and human SSc, and their gene signatures and functional pathways are identified in the course of disease. Genetic ablation of Trem2 in mice globally accelerates and aggravates skin fibrosis, whereas transferring TREM2hi macrophages improves and alleviates skin fibrosis. Amazingly, we found that disease-associated TREM2+ MФs in skin fibrosis exhibit overlapping signatures with fetal skin counterparts in mice and human to maintain skin homeostasis, but each has merits in skin remodeling and development respectively. Conclusion: This study identifies that TREM2 acts as a functional molecule and a major signaling by which macrophage subpopulations play a protective role against fibrosis, and disease-associated TREM2+ MФs in skin fibrosis might undergo a fetal-like reprogramming similar to fetal skin counterparts.

Efficacy of Talh Honey, Whey Protein, and Collagen Based Novel Formulation Against Wound-Associated Skin Microbiota

Objective: This study aims to evaluate the efficacy of a novel wound-healing formulation composed of honey, whey protein, and collagenagainst the skin microbiota associated with delayed wound healing. Methods: A rat excisional model was employed to assess the wound-healing formulation. Pathogen contraction rates were measured onvarious days following the onset of wounds to investigate the formulation’s impact on microbial infection. The formulation, known for itsantimicrobial properties and rich in growth factors, was applied to promote cell proliferation, differentiation, and tissue repair. Results: The tested wound-healing formulation demonstrated significant effectiveness in promoting the wound-healing process in rats.The pathogen contraction rates exhibited positive outcomes, indicating the formulation’s potential in addressing microbial infectionsassociated with delayed wound healing. Conclusion: This study underscores the promising therapeutic potential of the wound-healing formulation comprising honey, wheyprotein, and collagen. The observed positive effects on microbial infection and wound recovery suggest that this formulation could serveas a valuable intervention in managing delayed wound healing, particularly in conditions such as diabetes, immunosuppressive treatments, and obesity.

Expression and Correlation of HER2/P53/VEGF in Marjolin's Ulcer.

Marjolin's ulcer is described as malignant lesions developed in the injured skin, which can cause several kinds of malignancies. Our results showed that no HER2 but p53 was detected in Majorlin's ulcer samples. Meanwhile, by statistical analysis, we found that the positive rate of p53 in Majorlin's ulcer samples was associated with the pathological type of ulcer canceration and degree of tumor differentiation. The positive expression rate of vascular endothelial growth factor (VEGF) was 62.5% in poorly differentiated squamous cell carcinoma (SCC), 39.4% in moderately differentiated SCC, and 66.7% in well-differentiated SCC, respectively. Furthermore, some cases of Majorlin's ulcer with positive P53 were negative for VEGF, while some cases with positive VEGF were negative for P53. Image superposition showed that VEGF expression was absent or minimal in p53-positive cases. However, P53 was not expressed or rarely expressed in VEGF-positive cases. Our results of this study will suggest that P53 can be used as the mark of Marjolin's ulcer differentiation, and there may be some interaction between P53 and VEGF in Marjolin's ulcer. The regulation of microenvironment in the oncogenesis, progression, and differentiation of Marjolin's ulcer is complex and needs further study.

Biocompatible, robust, waterproof and breathable PDMS-based PU fibrous membranes for potential application in wound dressing

Wound dressings, an effective tool for repairing injured skin and protecting it from secondary damage, have been widely manufactured. However, the design of wound dressings with waterproofness, breathability, mechanical robustness, and excellent biocompatibility remains a challenge due to the imbalance between the multiple desirable properties. Herein, a strategy is proposed to fabricate biocompatible membranes via a facile one-step electrospinning method. Polydimethylsiloxane-based polyurethane is effectively prepared to form durable hydrophobic surfaces, resulting in a high degree of hydrophobicity (141.0° water contact angle). The porous structure is enhanced by adjusting the solution concentration and heat treatment temperature, resulting in an optimal water vapor transmission rate of 8.2 kg·m−2·h−1. Additionally, the membrane exhibits a hydrostatic pressure of 52.3 kPa, which is approximately 14.1 times greater than that of PU fibrous membrane, and an enhanced tensile strength of 6.60 MPa. Moreover, the membrane can be utilized in a wide temperature range from − 123 °C to 160 °C due to its low glass transition temperature and exceptional thermal stability. Significantly, both in vitro and in vivo studies confirmed the remarkable biocompatibility and minimal toxicity to normal cells and mice skin. Our work presents a new approach to designing waterproof and breathable biomaterials with high mechanical strength, thereby enhancing their performance and functionality in the biomedical field, particularly in wound dressing applications.

Characterization of Cell Type Abundance and Gene Expression Timeline from Burned Skin Bulk Transcriptomics by Deconvolution.

Currently, no timeline of cell heterogeneity in thermally injured skin has been reported. In this study, we proposed an approach to deconvoluting cell type abundance and expression from skin bulk transcriptomics with cell type signature matrix constructed by combining independent normal skin and peripheral blood scRNA-seq datasets. Using CIBERSORTx group mode deconvolution, we identified perturbed cell type fractions and cell type-specific gene expression in three stages postthermal injury. We found an increase in cell proportions and cell type-specific gene expression perturbation of neutrophils, macrophages, and endothelial cells and a decrease in CD4+ T cells, keratinocytes, melanocyte, and fibroblast cells, and cell type-specific gene expression perturbation postburn injury. Keratinocyte, fibroblast, and macrophage up regulated genes were dynamically enriched in overlapping and distinct Gene Ontology biological processes including acute phase response, leukocyte migration, metabolic, morphogenesis, and development process. Down-regulated genes were enriched in Wnt signaling, mesenchymal cell differentiation, gland and axon development, epidermal morphogenesis, and fatty acid and glucose metabolic process. We noticed an increase in the expression of CCL7, CCL2, CCL20, CCR1, CCR5, CCXL8, CXCL2, CXCL3, MMP1, MMP8, MMP3, IL24, IL6, IL1B, IL18R1, and TGFBR1 and a decrease in expression of CCL27, CCR10, CCR6, CCR8, CXCL9, IL37, IL17, IL7, IL11R, IL17R, TGFBR3, FGFR1-4, and IGFR1 in keratinocytes and/or fibroblasts. The inferred timeline of wound healing and CC and CXC genes in keratinocyte was validated on independent dataset GSE174661 of purified keratinocytes. The timeline of different cell types postburn may facilitate therapeutic timing.

JAM-A-Modified ADSCs-Derived Exosomes Encapsulating miRNA Promote Wound Healing by Mediating Fibroblast Function

This study investigates the role of JAM-A-modified adipose-derived stem cell (ADSC)-derived exosomes encapsulating miRNAs in promoting wound healing by mediating fibroblast function. The effects of JAM-A-modified exosomes (JAMA-Exos) containing miR-21-3p, miR-152-3p, and miR-486-5p were examined on fibroblast migration, proliferation, and collagen expression in vitro. Scalded skin mouse models were used to assess the impact of these miRNA-encapsulated exosomes on skin healing. JAM-A-Exos modified by these miRNAs enhanced fibroblast migration, proliferation, and collagen production in vitro, with miR-21-3p having the most significant effect. In vivo, treatment with JAM-A-Exos containing these miRNAs greatly improved wound healing, reduced apoptosis, and increased collagen synthesis in the injured skin. MiR-21-3p showed the strongest promoting effect, and its impact gradually decreased after day 7 of treatment. These findings suggest that JAM-A-Exos modified with miR-21-3p, miR-152-3p, and miR-486-5p can effectively enhance wound healing by mediating fibroblast function and up-regulating collagen expression, offering a potential therapeutic option for skin wounds in clinical practice.

Bassia longifolia (= Madhuca longifolia): Isolation of flavan-3-ols and their contribution to the antibacterial and antidiabetic activity in vitro

Bassia longifoliaKOENIG (= Madhuca longifolia (L.) is an evergreen tree that is widely distributed throughout Nepal, India, and Sri Lanka. The bark has various traditional uses: as a paste in the treatment of cuts and wounds or internally as a decoction that is given to diabetic patients. Chemical-analytical and pharmacological investigations regarding the bark are not sufficiently available. We focused on the isolation of flavan-3-ols from the methanolic extract and their contribution to the described traditional uses in wound healing and diabetes treatment. Therefore, an antibacterial assay and an α-glucosidase assay were performed. The isolation process was performed by a combination of Sephadex®-, MCI®-Gel-, and RP-18 chromatography. The structures of the isolated compounds were elucidated by 1H- and 13C-NMR-spectroscopy including COSY, ROESY, HSQC, and HMBC methods. Optical characterization was performed by polarimetry and circular dichroism. Two monomeric, seven dimeric, six trimeric, and one tetrameric flavan-3-ols were found including one dimer and three trimers with rare epiafzelechin units. Two compounds were isolated for the first time. A fraction containing higher oligomeric and polymeric proanthocyanidins (PAs) was examined by 13C NMR spectroscopy and revealed an average degree of polymerization of 8–9. PA with cis-configurated subunits predominated at 90 % and the presence of further monohydroxylated flavan-3-ols was revealed. Minimal inhibitory concentrations (MICs) were investigated by the serial microdilution broth assay with Staphylococcus aureus. The bacterial suspension was inoculated on agar plates for determining the MICs. The α-glucosidase assay was performed in 96 well plates with α-glucosidase from Bacillus stearothermophilus. For the detection of enzyme inhibition, p-nitrophenyl-α-d-glucopyranoside was used as a substrate and after incubation absorbance was measured at 405 nm. Antibacterial effects were only found for fractions enriched with PAs or containing higher oligomeric and polymeric flavan-3-ols. All tested substances showed high α-glucosidase inhibition. Whereby 4β→8 conjugated dimers and the monomers showed the lowest inhibition, procyanidin (PC) B5 as 4β→6 conjugated and cinnamtannin A2 as tetrameric flavan-3-ol showed the highest. PAs with epiafzelechin units are rarely found in nature but their reoccurring appearance in B. longifolia could be characteristic of this plant. For its traditional uses, the antibacterial activity of the PA-enriched fractions could contribute to the wound healing process when applied to the injured skin. Moreover, all tested substances and fractions showed α-glucosidase inhibition, which could also explain the use of a decoction in the treatment of diabetes. In conclusion, pharmacological investigations could provide scientific evidence for traditional uses of B. longifolia.

Source efficiency of alpha-emitters applied to the skin surface.

Skin surface contamination by alpha-emitters is in itself not hazardous, but it would cause significant internal exposure in the case of injured skin as well as misjudgment in direct in vivo measurements (e.g. lung counting). The present study determined the source efficiency of alpha-emitters (241Am) applied to swine skin samples by analysing the observed alpha-particle energy spectra using advanced alpha-spectrometric simulation. Based on our results, the source efficiency was determined to be 0.365 (alpha-particle s-1 per Bq) on average (c.f. 0.5 in the case of no self-absorption in the source). The decrease in source efficiency would be attributed primarily to the radionuclide entering hair follicles or deep wrinkles. The degradation of the measured spectra from the skin samples indicates the penetration of some radionuclides into the upper layers of the stratum corneum. Although this study was limited to results obtained from swine skin samples, it suggests that irregularities in the skin surface may affect direct alpha measurements.

Accelerated Burn Healing in a Mouse Experimental Model Using α-Gal Nanoparticles.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burn healing, in the absence of regenerating epidermis, is infections, which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating the recruitment of macrophages into burns may contribute to faster regeneration of the epidermis, thus decreasing the risk of infections. This review describes a unique method for the rapid recruitment of macrophages into burns and the activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on the application of bio-degradable "α-gal" nanoparticles to burns. These nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/α-gal nanoparticle interaction activates the complement system, resulting in localized production of the complement cleavage peptides C5a and C3a, which are highly effective chemotactic factors for monocyte-derived macrophages. The macrophages recruited into the α-gal nanoparticle-treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophage cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on the healing of thermal injuries in the skin of anti-Gal-producing mice demonstrated a much faster recruitment of macrophages into burns treated with α-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns took ~12 days. α-Gal nanoparticles are non-toxic and do not cause chronic granulomas. These findings suggest that α-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.

TLR7 promotes skin inflammation via activating NFκB-mTORC1 axis in rosacea.

Rosacea is a chronic inflammatory skin disease originated from damaged skin barrier and innate/adaptive immune dysregulation. Toll-like receptors (TLRs) sense injured skin and initiate downstream inflammatory and immune responses, whose role in rosacea is not fully understood. Here, via RNA-sequencing analysis, we found that the TLR signaling pathway is the top-ranked signaling pathway enriched in rosacea skin lesions, in which TLR7 is highlighted and positively correlated with the inflammation severity of disease. In LL37-induced rosacea-like mouse models, silencing TLR7 prevented the development of rosacea-like skin inflammation. Specifically, we demonstrated that overexpressing TLR7 in keratinocytes stimulates rapamycin-sensitive mTOR complex 1 (mTORC1) pathway via NFκB signaling. Ultimately, TLR7/NFκ B/mTORC1 axis promotes the production of cytokines and chemokines, leading to the migration of CD4+T cells, which are infiltrated in the lesional skin of rosacea. Our report reveals the crucial role of TLR7 in rosacea pathogenesis and indicatesa promising candidate for rosacea treatments.

Combining Chitosan, Stearic Acid, and (Cu-, Zn-) MOFs to Prepare Robust Superhydrophobic Coatings with Biomedical Multifunctionalities.

There is an urgent need to develop a series of multifunctional materials with good biocompatibility, high mechanical strength, hemostatic properties, antiadhesion, and anti-infection for applications in wound care. However, successfully developing multifunctional materials is challenging. In this study, two superhydrophobic composite coatings with good biocompatibility, high mechanical strength, strong antifouling and blood repellency, fast hemostasis, and good antibacterial activity areprepared on cotton fabric surface by simple, green, and low-cost one-step dip-coating technology. The results discussed in the manuscript reveals that the two superhydrophobic composite coatings can maintain good mechanical stability, strong water repellency, and durability under various types of mechanical damage, high-temperature treatment, and long-term strong light irradiation. The coatings also exhibit good repellency to various solid pollutants, highly viscous liquid pollutants, and blood. In vitro and in vivo hemostatic experiments show that both composite coatings havegood hemostatic and anticlot adhesion properties. More importantly, this superhydrophobic coating prevents bacterial adhesion and growth and released Cu2+ and Zn2+ ions and chitosan to achieve bactericidal properties, thereby protecting injured skin from bacterial infection. The two superhydrophobic coatings enhance the antifouling, antiadhesion, hemostatic, and antibacterial functions of blood-repellent dressings and therefore have broad application prospects in medical and textile fields.

Hydrogel-Containing Biogenic Silver Nanoparticles: Antibacterial Action, Evaluation of Wound Healing, and Bioaccumulation in Wistar Rats.

Wound infections are feared complications due to their potential to increase healthcare costs and cause mortality since multidrug-resistant bacteria reduce treatment options. This study reports the development of a carbomer hydrogel containing biogenic silver nanoparticles (bioAgNPs) and its effectiveness in wound treatment. This hydrogel showed in vitro bactericidal activity after 2 h, according to the time-kill assay. It also reduced bacterial contamination in rat wounds without impairing their healing since the hydrogel hydrophilic groups provided hydration for the injured skin. The high number of inflammatory cells in the first days of the skin lesion and the greater degree of neovascularization one week after wound onset showed that the healing process occurred normally. Furthermore, the hydrogel-containing bioAgNPs did not cause toxic silver accumulation in the organs and blood of the rats. This study developed a bioAgNP hydrogel for the treatment of wounds; it has a potent antimicrobial action without interfering with cicatrization or causing silver bioaccumulation. This formulation is effective against bacteria that commonly cause wound infections, such as Pseudomonas aeruginosa and Staphylococcus aureus, and for which new antimicrobials are urgently needed, according to the World Health Organization's warning.

Preparation of quaternized N-halamine modified graphene oxide based antibacterial hydrogel and wound healing of bacterial infection

In clinical practice, the wound on the surface of the skin is prone to bacterial infection, for which healing of infected wounds has always been a tremendous challenge for clinics and research institutions. We developed a multifunctional bactericidal, recyclable, and slow-release graphene oxide-based hydrogel for bacterial wound healing and real-time monitoring of bacterial infection in this study. At the same time, the material has a sensing function, which can be used in the connection between the injured skin and the continuous detection equipment. QNGH (quaternarized N-halamine-grafted GO hydrogel) is manufactured by hydrogen bonding between quaternized N-halamine-modified graphene oxide and polyvinyl alcohol (PVA). The results show that in the mouse model of full-thickness skin repair, the hydrogel can continuously release germicidal ions and recyclability, promoting wound healing and contraction. Further, the graphene oxide-based hydrogel has excellent strain sensing performance. It detects the bending and stretching movements of different parts of the human body quickly, stably, and sensitively to show an excellent real-time monitoring performance of human motion. The sensing function of the hydrogel further broadens its application field. Therefore, this hydrogel material is expected to be a candidate material for sensing devices at the wound.

Protective role of stratum corneum in percutaneous Leptospira infection in a hamster model

Leptospira enters humans and animals through injured skin or mucous membranes by direct or indirect contact with urine excreted from infected reservoirs. Individuals with cut or scratched skin are at high risk of infection and are recommended to be protected from contact with Leptospira, but the risk of infection via skin without apparent wounds is unknown. We hypothesized that the stratum corneum of the epidermis might prevent percutaneous invasion of leptospires.We established a stratum corneum deficient model of hamsters using the tape stripping method. The mortality rate of hamsters lacking stratum corneum that were exposed to Leptospira was higher than that of controls with shaved skin, and was not significantly different from an epidermal wound group. These results indicated that the stratum corneum plays a critical role in protecting the host against leptospiral entry.We also examined the migration of leptospires through the monolayer of HaCaT cells (human keratinocyte cell line) using Transwell. The number of pathogenic leptospires penetrating the HaCaT cell monolayers was higher than that of non-pathogenic leptospires. Furthermore, scanning and transmission electron microscopic observations revealed that the bacteria penetrated the cell monolayers through both intracellular and intercellular routes. This suggested that pathogenic Leptospira can migrate easily through keratinocyte layers and is associated with virulence.Our study further highlights the importance of the stratum corneum as a critical barrier against the invasion of Leptospira found in contaminated soil and water. Hence, preventative measures against contact infection should be taken, even without visible skin wounds.

Three-Dimensional Artificial Skin Construct Bioprinted with a Marine-Based Biocomposite.

A variety of artificial skin scaffolds, including 3D-bioprinted constructs, have been widely studied for regenerating injured skin tissue. Here, we devised a new composite biomaterial ink using fish-skin-based decellularized extracellular matrices (dECM) from tilapia and cod fish. The composition of the biocomposite mixture was carefully selected to obtain a mechanically stable and highly bioactive artificial cell construct. In addition, the decellularized extracellular matrices were methacrylated, followed by exposure to UV light to initiate photo-cross-linking. Porcine-skin-based dECMMa (pdECMMa) and tilapia-skin-based dECMMa (tdECMMa) biomaterials were used as controls. Assessment of various biophysical parameters and in vitro cellular activities, including cytotoxicity, wound healing ability, and angiogenesis, showed that the biocomposite exhibited much higher cellular activities compared to the controls owing to the synergistic effect of the favorable biophysical properties of tdECMMa and bioactive components (collagen, glycosaminoglycans (GAGs), elastin, and free fatty acids) from the decellularized cod skin. Furthermore, the skin constructs bioprinted using the bioinks exhibited more than 90% cell viability, performed with 3 days of submerged culture and then 28 days of air-liquid culture. For all cell constructs, the expression of cytokeratin 10 (CK10) was observed on the top surface of the epidermal layer, and cytokeratin 14 (CK14) was detected in the lower section of the keratinocyte layer. However, more developed CK10 and CK14 antibodies were observed in the cell-laden biocomposite construct [tilapia-skin-based dECMMa with cod-skin-based dECM] than in the controls [porcine-skin-based dECMMa (pdECMMa) and tilapia-skin-based dECMMa (tdECMMa)]. Based on these results, we believe that the fish-skin-based biocomposite construct is a potential biomaterial ink for skin regeneration.