Intraluminal release of citrullinated histone 3 from various cellular origins coincides with microvascular thrombosis in burn wounds.

Loss of perfusion in the burn wound might cause wound deepening and impaired healing. We previously showed persistent microvascular thrombosis coinciding with intraluminal neutrophils extracellular traps in human burned skin. This study investigates the presence of intraluminal citrullinated histone 3 (H3cit) from different cellular origins (neutrophils, monocytes, and lymphocytes) in relation to microvascular thrombosis of burn wounds. Eschar was obtained from burn patients (n = 18) 6-40 days postburn with a mean total burned body surface area of 23%. Microvascular presence of tissue factor (TF), factor XII (FXII) and thrombi was assessed by immunohistochemistry. Intramicrovascular cell death was analyzed via immunofluorescent microscopy, combining antibodies for neutrophils (MPO), monocytes (CD14), and lymphocytes (CD45) with endothelial cell markers CD31 and H3cit. Significantly increased microvascular expression of TF, FXII, and thrombi (CD31+) was found in all eschar samples compared with control uninjured skin. Release of H3cit from different cellular origins was observed in the lumen of the dermal microvasculature in the eschar tissue 7-40 days postburn, with release from neutrophilic origin being 2.7 times more abundant. Intraluminal presence of extracellular H3cit colocalizing with either MPO, CD14, or CD45 is correlated to increased microvascular thrombosis in eschar of burn patients.

Mechanical stretch preconditioned adipose-derived stem cells elicit polarization of anti-inflammatory M2-like macrophages and improve chronic wound healing.

Transplantation of adipose-derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti-inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M-CSF) from ASCs, a chemokine that is linked to anti-inflammatory M2-like macrophages polarization. When the MS-ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS-ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.

Dermal white adipose tissue: Development and impact on hair follicles, skin defense, and fibrosis.

Dermal white adipose tissue (DWAT) is a distinctive adipose depot located within the lower dermis of the skin. Its significance as an ancillary fat in skin homoeostasis has recently received increased attention. New research has revealed that DWAT responses to skin pathology and physiology changes, impacting skin development, hair cycling, defense mechanisms, and fibrotic conditions. In this review, we explore the developmental process of DWAT and the adipose commitment timing of hypodermal. We explore the development process of DWAT and its pivotal role in regulating the hair cycle. We conclude the antibacterial activity and reversible dedifferentiation of dermal adipocytes in response to skin defense. Furthermore, we underscore the potentially crucial yet underestimated anti-fibrotic functions of DWAT-derived adipokines and adipocyte-myofibroblast transition.

Bioengineered MSCCxcr2 transdifferentiated keratinocyte-like cell-derived organoid potentiates skin regeneration through ERK1/2 and STAT3 signaling in diabetic wound.

Skin regeneration is severely compromised in diabetic foot ulcers. Allogeneic mesenchymal stem cell (MSC) transplantation is limited due to the poor engraftment, mitogenic, and differentiation potential in the harsh wound microenvironment. Thus, to improve the efficacy of cell therapy, the chemokine receptor Cxcr2 was overexpressed in MSCs (MSCCxcr2). CXCL2/CXCR2 axis induction led to the enhanced proliferation of MSCs through the activation of STAT3 and ERK1/2 signaling. Transcriptional upregulation of FGFR2IIIb (KGF Receptor) promoter by the activated STAT3 and ERK1/2 suggested trans-differentiation of MSCs into keratinocytes. These stable MSCCxcr2 in 2D and 3D (spheroid) cell cultures efficiently transdifferentiated into keratinocyte-like cells (KLCs). An in vivo therapeutic potential of MSCCxcr2 transplantation and its keratinocyte-specific cell fate was observed by accelerated skin tissue regeneration in an excisional splinting wound healing murine model of streptozotocin-induced type 1 diabetes. Finally, 3D skin organoids generated using MSCCxcr2-derived KLCs upon grafting in a relatively avascular and non-healing wounds of type 2 diabetic db/db transgenic old mice resulted in a significant enhancement in the rate of wound closure by increased epithelialization (epidermal layer) and endothelialization (dermal layer). Our findings emphasize the therapeutic role of the CXCL2/CXCR2 axis in inducing trans-differentiation of the MSCs toward KLCs through the activation of ERK1/2 and STAT3 signaling and enhanced skin regeneration potential of 3D organoids grafting in chronic diabetic wounds.

Precise spatial structure impacts antimicrobial susceptibility of S. aureus in polymicrobial wound infections.

A hallmark of microbial ecology is that interactions between members of a community shape community function. This includes microbial communities in human infections, such as chronic wounds, where interactions can result in more severe diseases. Staphylococcus aureus is the most common organism isolated from human chronic wound infections and has been shown to have both cooperative and competitive interactions with Pseudomonas aeruginosa. Still, despite considerable study, most interactions between these microbes have been characterized using in vitro well-mixed systems, which do not recapitulate the infection environment. Here, we characterized interactions between S. aureus and P. aeruginosa in chronic murine wounds, focusing on the role that both macro- and micro-scale spatial structures play in disease. We discovered that S. aureus and P. aeruginosa coexist at high cell densities in murine wounds. High-resolution imaging revealed that these microbes establish a patchy distribution, only occupying 5 to 25% of the wound volume. Using a quantitative framework, we identified a precise spatial structure at both the macro (mm)- and micro (µm)-scales, which was largely mediated by P. aeruginosa production of the antimicrobial 2-heptyl-4-hydroxyquinoline N-oxide, while the antimicrobial pyocyanin had no impact. Finally, we discovered that this precise spatial structure enhances S. aureus tolerance to aminoglycoside antibiotics but not vancomycin. Our results provide mechanistic insights into the biogeography of S. aureus and P. aeruginosa coinfected wounds and implicate spatial structure as a key determinant of antimicrobial tolerance in wound infections.

Antioxidant and Immunomodulatory Polymer Vesicles for Effective Diabetic Wound Treatment through ROS Scavenging and Immune Modulating.

Chronic diabetic wound patients usually show high glucose levels and systemic immune disorder, resulting in high reactive oxygen species (ROS) levels and immune cell dysfunction, prolonged inflammation, and delayed wound healing. Herein, we prepared an antioxidant and immunomodulatory polymer vesicle for diabetic wound treatment. This vesicle is self-assembled from poly(ε-caprolactone)36-block-poly[lysine4-stat-(lysine-mannose)22-stat-tyrosine)16] ([PCL36-b-P[Lys4-stat-(Lys-Man)22-stat-Tyr16]). Polytyrosine is an antioxidant polypeptide that can scavenge ROS. d-Mannose was introduced to afford immunomodulatory functions by promoting macrophage transformation and Treg cell activation through inhibitory cytokines. The mice treated with polymer vesicles showed 23.7% higher Treg cell levels and a 91.3% higher M2/M1 ratio than those treated with PBS. Animal tests confirmed this vesicle accelerated healing and achieved complete healing of S. aureus-infected diabetic wounds within 8 days. Overall, this is the first antioxidant and immunomodulatory vesicle for diabetic wound healing by scavenging ROS and regulating immune homeostasis, opening new avenues for effective diabetic wound healing.

Fish collagen sponge with human umbilical cord mesenchymal stem cells for diabetic wound repair in rats.

Stem cell therapy offers a novel approach to treating difbetic foot ulcers. Fish skin decellularized matrix, a type I collagen, provides a promising carrier for stem cells, creating a supportive microenvironment that enhances cell survival and therapeutic potential. This study aims to investigate the effects and mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) loaded onto a fish collagen sponge for wound healing in diabetic rats. The study evaluates stem cell-loading efficiency with fish collagen sponge in vitro, assesses material distribution on diabetic rat wounds, and establishes a wound model. Rats are divided into the Self-healing group, Fish collagen sponge group, and Sponge loaded with HUCMSCs group. Therapeutic effects are evaluated through various analyses, including histopathology and reverse transcription polymerase chain reaction for collagen-related gene expression levels. Compared to the self-healing group, both the fish collagen group and the composite group show faster wound repair and improved healing outcomes. The composite group exhibits superior wound healing quality, with fish collagen contributing to enhanced tissue regeneration through collagen regulation at the wound site. Loading HUCMSCs onto a fish collagen sponge shows promise for treating diabetic wounds by addressing nutrient deficiency and cell supply issues, offering potential benefits for patients undergoing treatment.

Controversies in the pathophysiology of leg ulcers in sickle cell disease.

Patients with sickle cell disease (SCD) often experience painful vaso-occlusive crises and chronic haemolytic anaemia, as well as various acute and chronic complications, such as leg ulcers. Leg ulcers are characterized by their unpredictability, debilitating pain and prolonged healing process. The pathophysiology of SCD leg ulcers is not well defined. Known risk factors include male gender, poor social conditions, malnutrition and a lack of compression therapy when oedema occurs. Leg ulcers typically start with spontaneous pain, followed by induration, hyperpigmentation, blister formation and destruction of the epidermis. SCD is characterized by chronic haemolysis, increased oxidative stress and decreased nitric oxide bioavailability, which promote ischaemia and inflammation and consequently impair vascular function in the skin. This cutaneous vasculopathy, coupled with venostasis around the ankle, creates an ideal environment for local vaso-occlusive crises, which can result in the development of leg ulcers that resemble arterial ulcers. Following the development of the ulcer, healing is hindered as a result of factors commonly observed in venous ulceration, including venous insufficiency, oedema and impaired angiogenesis. All of these factors are modulated by genetic factors. However, our current understanding of these genetic factors remains limited and does not yet enable us to accurately predict ulceration susceptibility.

Substrate stiffness regulates type II diabetic fibroblast phenotype and metabolic activity.

In people living with diabetes, impaired wound healing is a major concern as the formation of ulcerated wounds can drastically reduce both the effectiveness of the healing process and the quality of life of the patient. The healing of dermal wounds in particular involves a patient's fibroblasts building up a strong extracellular matrix of mostly collagen I and collagen III fibers, which the cells of diabetic patients struggle to do. Extracellular matrix stiffness, and growth substrate stiffness in general, have already been shown to have a significant effect on the growth and development of already existent cells, and in diabetic dermal fibroblasts, morphological and physiological characteristics associated with the healing process appear to be altered from their healthy state. In this study we utilized a PDMS surface with a stiffness comparable to a wound environment (16 kPa) and a softer surface (0.2 kPa) to study the effects on diabetic and normal fibroblasts. We found diabetic fibroblast morphology became more fibroblast like when placed on the softer surfaces. This was demonstrated by a 15.6% decrease in the aspect ratio and a 16.4% increase in the circularity. The presence of the stress fibers was decreased by 19.4% in diabetic fibroblasts when placed on a softer surface. The proliferation rate of the diabetic fibroblasts was unaffected by the change in stiffness, but the metabolic activity greatly decreased (76%) on the softer surface. The results suggest that the softer surface may have a therapeutic effect on diabetic fibroblast metabolic activity. Further studies could focus on investigating this relationship and utilize it in tunable biomaterials to facilitate and accelerate the healing process for diabetic wounds.

A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Multifunctional Hydrogel Microneedle Patches Modulating Oxi-inflamm-aging for Diabetic Wound Healing.

Oxidative stress, chronic inflammation, and immune senescence are important pathologic factors in diabetic wound nonhealing. This study loads taurine (Tau) into cerium dioxide (CeO2) to develop CeO2@Tau nanoparticles with excellent antioxidant, anti-inflammatory, and anti-aging properties. To enhance the drug penetration efficiency in wounds, CeO2@Tau is encapsulated in gelatin methacryloyl (GelMA) hydrogel to prepare CeO2@Tau@Hydrogel@Microneedle (CTH@MN) patch system. Microneedle technology achieves precise and efficient delivery of CeO2@Tau, ensuring their deep penetration into the wound tissue for optimal efficacy. Rigorous in vitro and in vivo tests have confirmed the satisfactory therapeutic effect of CTH@MN patch on diabetic wound healing. Mechanistically, CTH@MN attenuates oxidative damage and inflammatory responses in macrophages by inhibiting the ROS/NF-κB signaling pathway. Meanwhile, CTH@MN activated autophagy-mediated anti-aging activity, creating a favorable immune microenvironment for tissue repair. Notably, in a diabetic mouse wound model, the multifunctional CTH@MN patch significantly promotes wound healing by systematically regulating the oxidation-inflammation-aging (oxi-inflamm-aging) pathological axis. In conclusion, the in-depth exploration of the CTH@MN system in this study provides new strategies and perspectives for treating diabetic non-healing wounds.

Multifunctional Gold Nanozyme-Engineered Amphotericin B for Enhanced Antifungal Infection Therapy.

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.

Guiding the Path to Healing: CuO2 -Laden Nanocomposite Membrane for Diabetic Wound Treatment.

Diabetic chronic wounds pose significant clinical challenges due to their characteristic features of impaired extracellular matrix (ECM) function, diminished angiogenesis, chronic inflammation, and increased susceptibility to infection. To tackle these challenges and provide a comprehensive therapeutic approach for diabetic wounds, the first coaxial electrospun nanocomposite membrane is developed that incorporates multifunctional copper peroxide nanoparticles (n-CuO2 ). The membrane's nanofiber possesses a unique "core/sheath" structure consisting of n-CuO2 +PVP (Polyvinylpyrrolidone)/PCL (Polycaprolactone) composite sheath and a PCL core. When exposed to the wound's moist environment, PVP within the sheath gradually disintegrates, releasing the embedded n-CuO2 . Under a weakly acidic microenvironment (typically diabetic and infected wounds), n-CuO2 decomposes to release H2 O2 and Cu2+ ions and subsequently produce ·OH through chemodynamic reactions. This enables the anti-bacterial activity mediated by reactive oxygen species (ROS), suppressing the inflammation while enhancing angiogenesis. At the same time, the dissolution of PVP unveils unique nano-grooved surface patterns on the nanofibers, providing desirable cell-guiding function required for accelerated skin regeneration. Through meticulous material selection and design, this study pioneers the development of functional nanocomposites for multi-modal wound therapy, which holds great promise in guiding the path to healing for diabetic wounds.

Development and functional testing of a novel in vitro delayed scratch closure assay.

As the development of chronic wound therapeutics continues to expand, the demand for advanced assay systems mimicking the inflammatory wound microenvironment in vivo increases. Currently, this is performed in animal models or in in vitro cell-based models such as cell culture scratch assays that more closely resemble acute wounds. Here, we describe for the first time a delayed scratch closure model that mimics some features of a chronic wound in vitro. Chronic wounds such as those suffered by later stage diabetic patients are characterised by degrees of slowness to heal caused by a combination of continued localised physical trauma and pro-inflammatory signalling at the wound. To recreate this in a cell-based assay, a defined physical scratch was created and stimulated by combinations of pro-inflammatory factors, namely interferon, the phorbol ester PMA, and lipopolysaccharide, to delay scratch closure. The concentrations of these factors were characterised for commonly used human keratinocyte (HaCaT) and dermal fibroblast (HDF) cell lines. These models were then tested for scratch closure responsiveness to a proprietary healing secretome derived from human Wharton's jelly mesenchymal stem cells (MSCs) previously validated and shown to be highly effective on closure of acute wound models both in vitro and in vivo. The chronically open scratches from HaCaT cells showed closure after exposure to the MSC secretome product. We propose this delayed scratch closure model for academic and industrial researchers studying chronic wounds looking for responsiveness to drugs or biological treatments prior to testing on explanted patient material or in vivo.

Histomorphometric analysis of excisional cutaneous wounds with different diameters in an animal model.

The skin wound model in rats is a fundamental stage in preclinical trials, but there is a lack of standardization in these trials regarding the initial wound area, making analysis and comparison between studies difficult. Therefore, this study evaluates the healing progression of excisional skin lesions of varying diameters in Wistar rats, aiming to identify the optimal wound size for monitoring treatment effects on wound healing. Excisions of 0.8, 1.5, 2.0 and 3.0 cm in diameter were made on the back of the animals. Thirty animals were used per treatment and evaluated on days 3, 7, 10, 14 and 21 after surgery. The lesions were cleaned daily with saline solution until they were completely closed. The 0.8 cm group showed complete repair on D14, while in the other groups, the wounds persisted until day 21, with a reddened surface and no complete epidermal coverage, but with greater keratinization and presence of appendages in the 1.5 cm lesions. Therefore, as a standardization model for creating skin wounds, we suggest using 1.5 or 2.0 cm excisions, considering that 0.8 cm wounds close very early and 3.0 cm wounds, although behaving similarly to 2.0 cm wounds, are more invasive for the animals. The 1.5 cm model proved to be suitable for closure within 21 days. When evaluating a product intended to accelerate wound healing, 2.0 cm lesions are recommended to assess the effectiveness of the treatment.

Housing Characteristics and Hospital Admissions due to Falls on Stairs: A National Birth Cohort Study.

OBJECTIVE: To assess associations between housing characteristics and risk of hospital admissions related to falls on/from stairs in children, to help inform prevention measures. STUDY DESIGN: An existing dataset of birth records linked to hospital admissions up to age 5 for a cohort of 3 925 737 children born in England between 2008 and 2014, was linked to postcode-level housing data from Energy Performance Certificates. Association between housing construction age, tenure (eg, owner occupied), and built form and risk of stair fall-related hospital admissions was estimated using Poisson regression. We stratified by age (<1 and 1-4 years), and adjusted for geographic region, Index of Multiple Deprivation, and maternal age. RESULTS: The incidence was higher in both age strata for children in neighborhoods with homes built before 1900 compared with homes built in 2003 or later (incidence rate ratio [IRR], 1.40; 95% CI, 1.10-1.77 [age <1 year], 1.20; 95% CI, 1.05-1.36 [age 1-4 years]). For those aged 1-4 years, the incidence was higher for those in neighborhoods with housing built between 1900 and 1929, compared with 2003 or later (IRR, 1.26; 95% CI, 1.13-1.41), or with predominantly social-rented homes compared with owner occupied (IRR, 1.21; 95% CI, 1.13-1.29). Neighborhoods with predominantly houses compared with flats had higher incidence (IRR, 1.24; 95% CI, 1.08-1.42 [<1 year] and IRR 1.16; 95% CI, 1.08-1.25 [1-4 years]). CONCLUSIONS: Changes in building regulations may explain the lower fall incidence in newer homes compared with older homes. Fall prevention campaigns should consider targeting neighborhoods with older or social-rented housing. Future analyses would benefit from data linkage to individual homes, as opposed to local area level.

Effects of mitochondrial transplantation on chronic pressure wound healing in a human patient.

BACKGROUND AIMS: Wound healing is a multistage process that requires a concerted effort of various cell types. The intricate processes involved in the healing of wounds result in high energy requirements. Furthermore, mitochondria play a crucial role in the healing process because of their involvement in neo angiogenesis, growth factor synthesis, and cell differentiation. It is unclear how mitochondria transplantation, a promising new approach, influences wound healing. METHODS: In this study, healthy autologous mitochondria obtained from skeletal muscle were injected into chronic pressure wounds as an intervention to promote wound healing. RESULTS: Mitochondrial transplantation accelerated wound healing by reducing wound size, increasing granulation tissue, and hastening epithelialization. CONCLUSIONS: This study is the first to demonstrate the therapeutic efficacy of mitochondrial transplantation in wound healing.

Analysis of risk factors related to chronic non-healing wound infection and the construction of a clinical prediction model.

This study is aimed to analyse the risk factors associated with chronic non-healing wound infections, establish a clinical prediction model, and validate its performance. Clinical data were retrospectively collected from 260 patients with chronic non-healing wounds treated in the plastic surgery ward of Shanxi Provincial People's Hospital between January 2022 and December 2023 who met the inclusion criteria. Risk factors were analysed, and a clinical prediction model was constructed using both single and multifactor logistic regression analyses to determine the factors associated with chronic non-healing wound infections. The model's discrimination and calibration were assessed via the concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Multivariate logistic regression analysis identified several independent risk factors for chronic non-healing wound infection: long-term smoking (odds ratio [OR]: 4.122, 95% CI: 3.412-5.312, p < 0.05), history of diabetes (OR: 3.213, 95% CI: 2.867-4.521, p < 0.05), elevated C-reactive protein (OR: 2.981, 95% CI: 2.312-3.579, p < 0.05), elevated procalcitonin (OR: 2.253, 95% CI: 1.893-3.412, p < 0.05) and reduced albumin (OR: 1.892, 95% CI: 1.322-3.112, p < 0.05). The clinical prediction model's C-index was 0.762, with the corrected C-index from internal validation using the bootstrap method being 0.747. The ROC curve indicated an area under the curve (AUC) of 0.762 (95% CI: 0.702-0.822). Both the AUC and C-indexes ranged between 0.7 and 0.9, suggesting moderate-to-good predictive accuracy. The calibration chart demonstrated a good fit between the model's calibration curve and the ideal curve. Long-term smoking, diabetes, elevated C-reactive protein, elevated procalcitonin and reduced albumin are confirmed as independent risk factors for bacterial infection in patients with chronic non-healing wounds. The clinical prediction model based on these factors shows robust performance and substantial predictive value.

Engineering of a decellularized bovine skin coated with antibiotics-loaded electrospun fibers with synergistic antibacterial activity for the treatment of infectious wounds.

An ideal antibacterial wound dressing with strong antibacterial behavior versus highly drug-resistant bacteria and great wound-healing capacity is still being developed. There is a clinical requirement to progress the current clinical cares that fail to fully restore the skin structure due to post-wound infections. Here, we aim to introduce a novel two-layer wound dressing using decellularized bovine skin (DBS) tissue and antibacterial nanofibers to design a bioactive scaffold with bio-mimicking the native extracellular matrix of both dermis and epidermis. For this purpose, polyvinyl alcohol (PVA)/chitosan (CS) solution was loaded with antibiotics (colistin and meropenem) and electrospun on the surface of the DBS scaffold to fabricate a two-layer antibacterial wound dressing (DBS-PVA/CS/Abs). In detail, the characterization of the fabricated scaffold was conducted using biomechanical, biological, and antibacterial assays. Based on the results, the fabricated scaffold revealed a homogenous three-dimensional microstructure with a connected pore network, a high porosity and swelling ratio, and favorable mechanical properties. In addition, according to the cell culture result, our fabricated two-layer scaffold surface had a good interaction with fibroblast cells and provided an excellent substrate for cell proliferation and attachment. The antibacterial assay revealed a strong antibacterial activity of DBS-PVA/CS/Abs against both standard strain and multidrug-resistant clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. Our bilayer antibacterial wound dressing is strongly suggested as an admirable wound dressing for the management of infectious skin injuries and now promises to advance with preclinical and clinical research.

IL-17 in wound repair: bridging acute and chronic responses.

Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation of white blood cell count, increased reactive oxygen species, and the potential risk of bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays a crucial role in regulating immune responses, has been identified as a promising target for treating inflammatory skin diseases. This review aims to delve deeper into the potential pathological role and molecular mechanisms of the IL-17 family and its pathways in wound repair. The intricate interactions between IL-17 and other cytokines will be discussed in detail, along with the activation of various signaling pathways, to provide a comprehensive understanding of IL-17's involvement in chronic wound inflammation and repair.