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Background: Clinical practice guidelines for the prevention of catheter associated urinary tract infection (CAUTI) recommend urinary catheter securement in critical patients although there is scant research on its effectiveness. Aim: To analyse whether securement of an indwelling urinary catheter (IUC) reduces the risk of CAUTI and meatal pressure injury among intensive care unit (ICU) patients and assess medical adhesive‐related skin injury (MARSI) associated with the securement device. Study Design: Open randomized controlled trial involving patients admitted to two ICUs in Spain. In the intervention group (n = 169 patients), the IUC was secured to the thigh using an in‐house device piloted as part of this trial. Controls (n = 181) received standard care, including non‐securement of the IUC. Barrier film spray was applied to the securement site with the aim of preventing MARSI. The definitions of the main outcomes were: CAUTI was diagnosed according to the criteria of the European Centre for Disease Prevention and Control, meatal pressure injury was categorized into four grades and MARSI was classified as either erythema or skin tears. Bivariate analysis and multivariate logistic regression were performed. Log‐rank and Cox regressions were used to compare risk over time to CAUTI and meatal pressure injury in the two groups. Results: Data from 350 patients were analysed, 169 (48.29%) from IG and 181 (51.71%) from CG. In the multiple logistic regression analysis, IUC securement was an independent protective factor against both CAUTI (RR = 0.2, 95% CI [0.05, 0.67]) and meatal pressure injury (RR = 0.31, 95% CI [0.15, 0.58]). The incidence of MARSI was 7.1%. Conclusion: Effective IUC securement significantly reduces the risk of CAUTI and meatal pressure injury among ICU patients. The in‐house device piloted in the present trial is simple for nurses to use, and the incidence of MARSI was low. These results underline the benefits of IUC securement. Relevance to Clinical Practice: Indwelling urinary catheter (IUC) securement reduces the risk of urinary tract infection. IUC securement helps prevent meatal pressure injury. IUC securement with in‐house devices is safe and effective. [ABSTRACT FROM AUTHOR]

Background: Mechanical force skin injuries are common for critical care patients, especially neonates. Currently, identification and severity assessments of injuries are dependent on clinical experience and/or utilization of severity tools. Compared with adults, neonates sustain skin injuries in different anatomical locations and have decreased layers of healthy tissue (from 0.9 to 1.2 mm) creating questions around direct application of adult injury severity scales reliant on visual assessment. Aim: The aim of this scoping review (ScR) was to investigate severity scales used to report hospital acquired skin injuries for neonates. Methods: This study utilized the 2015 Joanna Briggs Institute methodology for scoping reviews and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Scoping Reviews extension. PubMed, CINAHL, COCHRANE Central, Scopus, and the reference lists of included studies were searched for studies published between 2001 and 2023, that included severity scales use within neonatal population. Two authors independently identified studies for full review, data extraction, and quality assessment. Results: A systematic database search returned 1163 records. After full test review of 109 studies, 35 studies were included. A majority of studies included were cohort or action research and conducted in the United States of America. Most studies (57%, n = 20) reported skin injuries acquired throughout the body, 14 (40%) of the studies reported the nasal area alone and one study reported no anatomical location. A total of nine severity scales or combination of scales were utilized within studies (n = 31) and four studies did not report a scale. Various versions of scales from the National Pressure Ulcer Advisory Panel (n = 16), European Pressure Ulcer Advisory Panel (n = 8) or Neonatal Skin Condition Score (n = 4) were reported, compared with locally developed classifications/scales (n = 4). Scales were predominantly of ordinal grouping (74%, n = 26) or categorical assessment (14%, n = 5). Only one scale from 2004 was validated for neonates. Conclusion: Neonatal skin injuries will continue to be reported subjectively until severity scales are consistently applied or other measurements are identified to support assessment. Additionally, without skin injury assessment uniformity, critical examination of effectiveness of skin care treatment practices will have subjective comparison. This review suggests there is a need for consistent skin assessment and severity scales that are valid for the neonatal population and their unique skin considerations. Relevance to Clinical Practice: In the context of neonatal skin, with its unique characteristics and heightened risk for injury, clinicians must stage, categorise, and describe injury locations to provide objective information on injury severity. Given the risk for injuries across the entire body, including mucous membranes, describing the depth of the injury is essential regardless of the anatomical site. Although not originally designed for this population, a modified version of the National Pressure Injury Advisory Panel (NPIAP) classification system, which incorporates additional classifications (e.g., skin tears), remains the most applicable severity assessment system currently available. This should be supplemented by clinical images or detailed descriptive language (e.g., subtle redness) until rigorously validated severity and assessment scales, based on neonatal data, are developed—particularly for infants born at less than 27 weeks gestation. [Correction added on 25 October 2024, after first online publication: The Relevance to Clinical Practice subsection in Abstract has been added on this version.] [ABSTRACT FROM AUTHOR]

Objectives: The primary objective is to compare the imaging and surgical findings in a cohort of patients with suspected penile fracture (PF). Methods: Retrospective cohort study of all patients with suspected PF over an 11-year period at a tertiary referral andrology centre. All dedicated presurgical imaging with ultrasound (US) and MRI was analysed and correlated with intraoperative findings; alternative diagnoses were recorded. Results: One hundred and ninety-three patients were included. One hundred and four (54%) had alternative diagnoses to PF including dorsal vein rupture and haematoma. Ninety-nine (51%) underwent surgical exploration of which 89 (46%) had PF. US correctly confirmed the presence and marked the site of fracture in 92% of cases. MRI was primarily used as a problem-solving tool (13 cases) and demonstrated a more extensive injury than US (12 cases). The reported size of tunical defect on imaging was a median of 7 mm (IQR 4-10) significantly smaller than on exploration (median 20 mm, IQR 10-30; P < .0001). Conclusions: US has a high positive predictive value in the confirmation of PF. MRI improves the detection and characterizing the extent of injury. Imaging marking informs surgical incision but defect size is under appreciated on all imaging modalities. Advances in knowledge: Penile imaging has a high positive predictive value to not only confirm the diagnosis of PF but to stage the extent of injury and mark the skin, which impacts the surgical technique. Alternative diagnoses to fracture are common and imaging could prevent unnecessary surgical exploration. [ABSTRACT FROM AUTHOR]

The prevalence of chronic wounds continues to be a burden in human medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is commonly isolated from infected wounds. MRSA infections primarily delay healing by impairing local immune cell functions. This study aimed to investigate the potential of mesenchymal stromal cell (MSC)-secreted bioactive factors, defined as the secretome, to improve innate immune responses in vivo. MSCs were isolated from the bone marrow of horses, which serve as valuable translational models for wound healing. The MSC secretome, collected as conditioned medium (CM), was evaluated in vivo using mouse models of acute and MRSA-infected skin wounds. Punch biopsies were used to create two full-thickness skin wounds on the back of each mouse. Acute wounds were treated daily with control medium or bone marrow-derived MSC (BM-MSC) CM. The antibiotic mupirocin was administered as a positive control for the MRSA-infected wound experiments. Wounds were photographed daily, and wound images were measured to determine the rate of closure. Trichrome staining was carried out to examine wound tissue histologically, and immunofluorescence antibody binding was used to assess immune cell infiltration. Wounds in the MRSA-infected model were swabbed for quantification of bacterial load. Acute wounds treated with BM-MSC CM showed accelerated wound closure compared with controls, as illustrated by enhanced granulation tissue formation and resolution, increased vasculature and regeneration of hair follicles. This treatment also led to increased neutrophil and macrophage infiltration. Chronic MRSA-infected wounds treated with BM-MSC CM showed reduced bacterial load accompanied by better resolution of granulation tissue formation and increased infiltration of pro-healing M2 macrophages compared with control-treated infected wounds. Collectively, our findings indicate that BM-MSC CM exerts pro-healing, immunomodulatory and anti-bacterial effects on wound healing in vivo , validating further exploration of the MSC secretome as a novel treatment option to improve healing of both acute and chronic wounds, especially those infected with antibiotic-resistant bacteria. [Display omitted] [ABSTRACT FROM AUTHOR]

Skin injuries, whether due to trauma, burns, or chronic wounds, present a significant clinical challenge, highlighting the need for innovative regenerative therapies. This study focuses on the development and formulation of a drug-loaded hydrogel as a promising approach for skin regeneration. Hydrogel is designed to provide a supportive environment for cell proliferation, migration, and differentiation, while also delivering therapeutic agents to accelerate wound healing. Various biocompatible polymers and crosslinking methods are explored to optimize the hydrogel's mechanical properties, biodegradability, and drug release kinetics. Additionally, the study investigates the efficacy of different drugs, growth factors, and bioactive molecules in promoting angiogenesis, collagen synthesis, and tissue remodeling within the hydrogel scaffold. The developed drug-loaded hydrogel holds great potential for addressing a wide range of skin injuries and advancing the field of regenerative dermatology. In summary, hydrogels represent a promising avenue in skin regenerative medicine due to their unique properties that support tissue repair, drug delivery, and wound healing processes. Ongoing research continues to explore innovative applications of hydrogels to address challenges in skin regeneration and wound treatment effectively. [ABSTRACT FROM AUTHOR]

Dermal fibroblasts play a crucial role in the formation of granulation tissue in skin wounds. Consequently, the differentiation, migration, and proliferation of dermal fibroblasts are considered key factors in the skin wound healing process. However, in patients with diabetic foot ulcers, the proliferation and migration of fibroblasts are impaired by reactive oxygen species and inflammatory factors impair. Therefore, a novel magnetic gelatin-hesperidin microrobots drug delivery system was developed using microfluidics. The morphology, motility characteristics, and drug release of the microrobot were assessed, along with its impact on the proliferation and migration of human dermal fibroblasts under high-glucose conditions. Subjected to a rotating magnetic field, the microrobots exhibit precise, controllable, and flexible autonomous motion, achieving a maximum speed of 9.237 µm/s. In vitro drug release experiments revealed that approximately 78% of the drug was released within 30 min. It was demonstrated through cellular experiments that the proliferation of human dermal fibroblasts was actively promoted by the nanorobot, the migration ability of fibroblasts in a high-glucose state was enhanced, and good biocompatibility was exhibited. Hence, our study may provide a novel drug delivery system with significant potential for promoting the healing of diabetic foot wounds. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Design Method Results Conclusion Implications for the Profession and/or Patient Care Patient or Public Contribution Reporting Method Incontinence‐associated dermatitis poses a significant risk for sacral pressure injuries, infection and morbidity in healthcare settings. Despite the availability of best practice guidelines, implementation remains a challenge.To outline the implementation of a hospital‐wide programme using the Integrated Promoting Action on Research Implementation in Health Services framework to prevent and manage incontinence‐associated dermatitis and improve hospital‐acquired pressure injuries.This is an empirical research study using mixed methods.The study, conducted across surgical, medical and critical care wards between June and October 2023, aimed to address knowledge gaps, enhance clinical practice and evaluate the effectiveness of interventions. The implementation strategy included education modules, engagement of staff through focus groups and targeted interventions such as individualised toileting plans and structured skin care regimens. Data collection involved audits, incident reporting and clinician knowledge surveys.Findings indicate a reduction in hospital‐acquired incontinence‐associated dermatitis and pressure injuries postimplementation, with observed improvements in clinician knowledge. However, challenges including workload, skill mix and resource limitations were identified as barriers to implementation. The sustainability and scalability of the programme were emphasised, with ongoing monitoring and evaluation essential for long‐term success.This study underscores the importance of evidence‐based interventions, interdisciplinary collaboration and leadership support in improving patient outcomes and reducing healthcare costs associated with preventable skin injuries. Further research is needed to assess implementation in community settings and scale up interventions across healthcare networks.Analysing a hospital‐wide programme using the Integrated Promoting Action on Research Implementation in Health Service framework to prevent and manage incontinence‐associated dermatitis and improve hospital‐acquired pressure injuries, could help identify the challenges for delivering patient‐centred care.No patient or public involvement.To describe the implementation study, we referred to the StaRI Guideline.Trial Registration: This intervention study was applied to the whole population and was therefore not a trial and did not require trial registration. The study was considered low risk and the Human Research Ethics Application (HREA) was approved [ABSTRACT FROM AUTHOR]

Background: Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease's progression characteristics holds significant practical importance. Methods: Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer's protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe2+) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company. Results: In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe2+ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects. Conclusions: This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe2+ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Wound healing represents a complex biological process, critically important in clinical practice due to its direct implication in a patient's recovery and quality of life. Conservative wound management frequently falls short in providing an ideal environment for the optimal tissue regeneration, often resulting in extended healing periods and elevated risk of infection and other complications. The emerging biomaterials, particularly hydrogels, have shown substantial promise in addressing these challenges by offering properties such as biocompatibility, biodegradability, and the ability to cure wound environment. Recent advancements have highlighted the therapeutic potential of integrating cell-derived conditioned medium (CM) into hydrogel matrices. Cell-derived CM represents a rich array of bioactive molecules, demonstrating significant efficacy in modulating cellular activities crucial for wound healing, including cellular proliferation, migration, and angiogenesis. Methods: The methodology of this review adheres to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The review includes a selection of studies published within the last five years, focusing on in vivo experiments involving various types of skin injuries treated with topically applied hydrogels loaded with CM (H-CM). The search strategy refers to the PICO framework and includes the assessment of study quality by CAMARADES tool. Results: The systematic review represents a detailed evaluation of H-CM dressings wound healing efficiency based on the experimental results of cell-based assays and animal wound models. The study targets to reveal wound healing capacity of H-CM dressings, and provides a comparative data analysis, limitations of methods and discussions of H-CM role in advancing the wound healing therapy. Conclusions: The data presented demonstrate that H-CM is a promising material for advanced wound healing and regenerative medicine. These dressings possess proved in vitro/in vivo efficacy that highlights their strong clinical potential and paves the way to further investigations of H-CM formulations within clinical trials. [ABSTRACT FROM AUTHOR]

Protein-based wound dressings have garnered increasing interest in recent years owing to their distinct physical, chemical, and biological characteristics. The intricate molecular composition of proteins gives rise to unique characteristics, such as exceptional biocompatibility, biodegradability, and responsiveness, which contribute to the promotion of wound healing. Wound healing is an intricate and ongoing process influenced by multiple causes, and it consists of four distinct phases. Various treatments have been developed to repair different types of skin wounds, thanks to advancements in medical technology and the recognition of the diverse nature of wounds. This review has literature reviewed within the last 3–5 years—the recent progress and development of protein in wound dressings and the fundamental properties of an ideal wound dressing. Herein, the recent strides in protein-based state-of-the-art wound dressing emphasize the significant challenges and summarize future perspectives for wound healing applications. The graphical abstract illustrates different factors for protein-based dressing, wound healing phases, various responsive factors, and fundamental properties for an ideal wound dressing for wound healing applications. [ABSTRACT FROM AUTHOR]

Background: Burn wounds require optimal medical management due to associated psycho-emotional and socioeconomic impacts and severe pain. The use of synthetic and biological dressings improves healing and reduces burn wound complications. The present study aimed to compare the outcomes of using human amniotic membrane (hAM) dressings and conventional silver sulfadiazine (SSDZ) ointment dressings in the management of second-degree burn wounds. Methods: Fifty patients who participated in this clinical trial were divided into two groups via simple randomization. All the enrolled patients, who had burnt in the last 24 h, had thermal damage mechanisms and were suffering from less than 20% second-degree heat-burn wounds on the skin surface. The target group (n = 25) was treated with hAM, and the control group (n = 25) was treated with SSDZ ointment. The researcher-designed checklist was used to determine the clinical performance in the follow-up assessments on days 7, 14, and 30. Results: No significant differences were detected in terms of sex, age, or percentage of burn wounds (p > 0.05). Wound epithelialization at days 7, 14, and 30, scar formation, wound pigmentation, pain severity, analgesia requirements, and hospital stay length (on day 30) were significantly lower in the target group (treated with hAM) than in the control group (treated with SSDZ ointment) (p < 0.05). However, treatment costs in the target group ($170) were significantly higher than those in the control group ($71) (p < 0.001). Conclusion: Despite its higher cost, hAM, as a technology-based therapy dressing, demonstrates superiority over SSDZ ointment in terms of wound healing and pain management. [ABSTRACT FROM AUTHOR]

Staphylococcus pseudintermedius has been isolated from dogs, cats, and horses and is also known as an emergent zoonotic agent. We administered orbifloxacin, a fluoroquinolone, to treat bacterial infections of cutaneous wounds caused by excessive grooming of the skin in contact with the subcutaneous port of the subcutaneous ureteral bypass (SUB) system in a cat. However, after 80 days of treatment, a severe abscess was observed in the wound and fluoroquinolone-resistant S. pseudintermedius was isolated from the abscess. The isolate was identified as a novel sequence type (ST) 2660 and contained genes for leukocidins (lukS and lukF), exfoliative toxin (siet), and biofilm regulation (icaA and icaD). The isolate was resistant to macrolide, lincosamide, fluoroquinolone, and tetracycline classes. In addition, the isolate had strong biofilm-forming ability which significantly increased with culturing at 39 °C compared with that at 37 °C, suggesting that the isolate prefers a cats' body temperature as the optimal biofilm growth condition. Notably, the biofilms were increased in the presence of doxycycline with culturing at 39 °C. This study is the first report in Japan on the new sequence type of S. pseudintermedius isolated from a companion animal and clarifies the distinctive virulence of S. pseudintermedius. [ABSTRACT FROM AUTHOR]

Burn injuries are serious injuries that have a big impact on a person's health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair. [ABSTRACT FROM AUTHOR]

Bacterial infections, especially those from drug‐resistant strains, pose a significant threat to healing diabetic skin injuries, with current treatments being intricated and often unsatisfactory. Inspired by octopuses, a biomimetic material using α‐cyclodextrin (α‐CD) and polyethylene glycol (PEG) assembled with graphene oxide end‐capped polyrotaxanes (GO‐PR) is developed, where α‐CD mimics the flexible tentacles of an octopus. Further, α‐CD is cationically modified with polyethyleneimine (PEI) to resemble octopus suction cups, creating GO‐PRP, which effectively captures and adheres to bacteria. Importantly, to emulate an octopus's ink defense, GO‐PRP is used as a carrier for nitric oxide (NO), resulting in GO‐PRP/NONOate. Utilizing the photothermal conversion of GO, near‐infrared light exposure triggers rapid heating and NO release, providing efficient antibacterial activity and biofilm dispersion, significantly reducing inflammation in diabetic skin injuries in type I rats. During wound healing, sustained NO release promotes vascular endothelial growth factor production and blood vessel regeneration, enhancing collagen formation and shortening the healing time for diabetic skin infections. Thus, octopus‐inspired GO‐PRP/NONOate emerges as a novel biomaterial for treating drug‐resistant bacterial infections in diabetic wounds in the biomedical field. [ABSTRACT FROM AUTHOR]

Ubiquitin C‐terminal hydrolase L1 (UCHL1) plays vital roles in cell proliferation, angiogenesis, inflammation and oxidative stress. Nevertheless, it is unclear whether UCHL1 could regulate the biologic behaviour of cells and ultimately influences wound healing. We aim to illustrate the roles and the underlying mechanism of UCHL1 in cutaneous wound healing. Murine full‐thickness excisional wound model was utilised to study the effects of UCHL1 on wound healing through topical administration of the UCHL1 inhibitor LDN57444, followed by assessment of wound areas and histological alterations. Subsequently, ethynyldeoxyuridine, scratch and transwell assays were performed to examine fibroblast migration and proliferation. The extracellular matrix (ECM)‐related genes expression and transforming growth factor‐β (TGF‐β)/Smad signalling pathways activation were investigated by immuno‐fluorescent staining, Western blots and quantitative reverse transcription polymerase chain reaction. We identified elevated UCHL1 expression in non‐healing wound tissues. The UCHL1 expression displayed a dynamic change and reached a peak on Day‐7 post‐wounding during the healing process in mice. Cutaneous administration of LDN57444 promoted wound healing by facilitating collagen deposition, myofibroblast activation and angiogenesis. In vitro experiments demonstrated that UCHL1 concentration dependently inhibited migration, ECM synthesis and activation of human dermal fibroblasts, which was mechanistically related to downregulation of TGF‐β/Smad signalling. Furthermore, these effects could be reversed by TGF‐β inhibitor SB431542. Our findings reveal that UCHL1 is a negative regulator of cutaneous wound healing and considered as a novel prospective therapeutic target for effective wound healing. [ABSTRACT FROM AUTHOR]

Background/Objectives: Owing to the growing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to conventional antibiotics, the development of innovative therapeutic strategies for the treatment of MRSA-infected cutaneous wounds poses a significant challenge. Methods: Here, by using polyhydroxyalkanoates (PHA), emerging biodegradable and biocompatible polymers naturally produced by various microorganisms, we developed clindamycin-loaded PHA nanoparticles (Cly-PHA NPs) as a novel approach for the treatment of MRSA-infected cutaneous wounds. Results: Cly-PHA NPs were characterized in terms of mean particle size (216.2 ± 38.9 nm), polydispersity index (0.093 ± 0.03), zeta potential (11.3 ± 0.5 mV), and drug loading (6.76 ± 0.19%). Owing to the sustained release of clindamycin over 2 days provided by the PHA, Cly-PHA NPs exhibited potent antibacterial effects against MRSA. Furthermore, Cly-PHA NPs significantly facilitated wound healing in a mouse model of MRSA-infected full-thickness wounds by effectively eradicating MRSA from the wound bed. Conclusions: Therefore, our results suggest that Cly-PHA NPs offer a promising approach for combating MRSA infections and accelerating cutaneous wound healing. [ABSTRACT FROM AUTHOR]

Cannabis sativa emerges as a noteworthy candidate for its medicinal potential, particularly in wound healing. This review article explores the efficacy of cannabis oil in reducing reactive oxygen species (ROS) during the healing of acute and chronic wounds, comparing it to the standard treatments. ROS, produced from various internal and external sources, play a crucial role in wound development by causing cell and tissue damage. Understanding the role of ROS on skin wounds is essential, as they act both as signaling molecules and contributors to oxidative damage. Cannabis oil, recognized for its antioxidant properties, may help mitigate oxidative damage by scavenging ROS and upregulating antioxidative mechanisms, potentially enhancing wound healing. This review emphasizes ongoing research and the future potential of cannabis oil in dermatological treatments, highlighted through clinical studies and patent updates. Despite its promising benefits, optimizing cannabis oil formulations for therapeutic applications remains a challenge, underscoring the need for further research to realize its medicinal capabilities in wounds. [ABSTRACT FROM AUTHOR]

Background/Objectives: Wound healing relies on a coordinated process with the participation of different mediators. Natural products are a source of active compounds with healing potential. Isoorientin is a natural flavone recognized as having several pharmacological properties, such as anti-inflammatory effects, making it a potential treatment for wounds. We investigated the effect of isoorientin on the healing of excisional skin wounds. Methods: Male Swiss mice were subjected to the induction of excisional skin wounds (6 mm diameter) and treated with a vehicle (2% dimethyl sulfoxide in propylene glycol) or 2.5% isoorientin applied topically once a day for 14 days. The wound area was measured on days 0, 3, 7, and 14. Histopathological analyses were performed on the cicatricial tissue after 14 days. The myeloperoxidase activity and the interleukin-1β, tumoral necrosis factor (TNF)-α, and interleukin-6 concentrations were determined on the third day. Results: We observed that 3 days after the topical application of isoorientin, the lesion area was significantly smaller when compared to those of the vehicle (p < 0.01) and control (p < 0.05) groups. No difference was observed after 7 and 14 days of induction. Despite this, on day 14, histological analysis of cicatricial tissue from the animals treated with isoorientin showed reduced epidermal thickness (p < 0.001) and increased collagen deposition (p < 0.001). These effects were accompanied by decreased myeloperoxidase activity and interleukin-1β concentration on the third day of induction, without alteration in TNF-α and interleukin-6. Conclusions: The treatment with isoorientin promoted better tissue repair in excisional wounds in mice, which may be linked to the modulation of the early inflammatory response. [ABSTRACT FROM AUTHOR]

The article discusses the importance of wound dressings in clinical practice, focusing on the development of cooling wound dressings to regulate wound temperature and promote healing. Various functional polymer-based dressings with antibacterial and cooling properties are highlighted, showcasing their potential for skin tissue engineering and wound management. The integration of passive radiative cooling (PRC) properties into biocompatible dressings is emphasized, offering a noninvasive approach to wound care. The article also explores the use of nanomaterials, conductive polymers, and biodegradable materials in wound dressings, underscoring the need for further research to enhance clinical applications and patient outcomes. [Extracted from the article]

Background: The immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage‐related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established. Objective: This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions. Methods and results: Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage‐specific knockout of Trem2 (T2‐cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)‐4 binds directly to Trem2, inactivating MAPK/AP‐1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co‐culture of fibroblasts and macrophages showed that macrophages from T2‐cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing. Conclusions: These analyses offer novel insight into the role of IL‐4/Trem2 signalling as a mediator of myeloid cell‐fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing. [ABSTRACT FROM AUTHOR]

Background: Undesirable injuries during the intraoperative period, such as pressure injuries caused by improper positioning, medical devices, or adhesive tapes, can lead to patient harm and decreased satisfaction. This study aims to identify the risk factors of pressure injuries during the intraoperative period and the characteristics of these injuries. Methods: A retrospective case‑control study was conducted at King Khaled University Hospital in Riyadh, Saudi Arabia. Data were collected from the hospital incident reporting system and electronic medical records for incidents reported from January 1, 2022 to December 31, 2022. Inclusion criteria consisted of all patients with a reported pressure injury, including pressure ulcers, medical adhesive‑related skin injuries, or medical device‑related pressure injuries, occurring at least once during surgery. Results: Among the 113 patients, 57 (50.44%) had intraoperative pressure injuries (cases), while 56 (49.56%) did not (controls). The most common locations for pressure injuries were the lips (33.33%). Most of these injuries were classified as Medical Adhesive‑Related Skin Injury (61.40%). Stage 1 injuries were observed in 47 cases (82.46%), while Stage 2 injuries were observed in 10 cases (17.54%). Duration of surgery and device tightness were identified as significant risk factors (P < 0.001). Conclusion: This case‑control study identified the duration of surgery and device tightness as significant risk factors for intraoperative pressure injuries. The findings emphasize the importance of implementing evidence‑based prevention strategies. Healthcare professionals should prioritize staff education and training, while future research should focus on conducting prospective, multicenter studies and developing risk assessment tools and innovative medical devices. [ABSTRACT FROM AUTHOR]

Materials engineering has become an important tool in the field of hydrogel dressings used to treat difficult-to-heal wounds. Hydrogels filled with bioactive substances used as a targeted healing system are worthy of attention. Vitamin C has healing and supporting effects in the treatment of many skin problems. The aim of the research was to produce a hydrogel biomaterial enriched with ascorbic acid for use as a dressing for difficult-to-heal wounds. A total of four different dressings were developed, each with different modifications in each layer. The dressing with vitamin C in the third layer was shown to release vitamin C ions more slowly than the dressing with vitamin C in the first layer. The studies conducted have shown that the dressings containing vitamin C have, among other things, a higher compressive strength, are characterised by a lower relative shortening after the application of force and shorten without damage at a lower force than in the case of a dressing without vitamin C. The dressings designed have a very good stability in the temperature range of 18 °C to 60 °C. It was found that the higher the vitamin C content in the dressing, the greater the increase in the specific heat value of the transformations. Therefore, hydrogel dressings containing vitamin C may be candidates for local delivery of vitamin C to the skin and protection of the wound area. [ABSTRACT FROM AUTHOR]

Hydrogels have emerged as promising candidates for biomedical applications, especially in the treatment of skin wounds, as a result of their unique structural properties, highly tunable physicochemical properties, and excellent biocompatibility. The integration of smart-response features into hydrogels allows for dynamic responses to different external or internal stimuli. Therefore, this paper reviews the design of different smart-responsive hydrogels for different microenvironments in the field of skin wound therapy. First, the unique microenvironments of three typical chronic difficult-to-heal wounds and the key mechanisms affecting wound healing therapeutic measures are outlined. Strategies for the construction of internal stimulus-responsive hydrogels (e.g., pH, ROS, enzymes, and glucose) and external stimulus-responsive hydrogels (e.g., temperature, light, electricity, and magnetic fields) are highlighted from the perspective of the wound microenvironment and the in vitro environment, and the constitutive relationships between material design, intelligent response, and wound healing are revealed. Finally, this paper discusses the severe challenges faced by smart-responsive hydrogels during skin wound repair and provides an outlook on the combination of smart-responsive hydrogels and artificial intelligence to give scientific direction for creating and using hydrogel dressings that respond to stimuli in the clinic. [ABSTRACT FROM AUTHOR]

This study investigates the development and application of electrospun wound dressings based on polylactic acid (PLA) nanofibers, chitosan, and copper nanoparticles (CuNPs) for the treatment of purulent skin wounds. The materials were evaluated for their structural, antibacterial, and wound healing properties using an animal model. PLA/Ch-CuNPs demonstrated the most significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, surpassing the other tested materials. The integration of CuNPs into the nanofiber matrices not only enhanced the antimicrobial efficacy but also maintained the structural integrity and biocompatibility of the dressings. In vivo experiments using a rat model showed that PLA/Ch-CuNPs facilitated faster wound healing with reduced exudative and inflammatory responses compared to PLA alone or PLA-CuNPs. Histological and immunohistochemical assessments revealed that the combination of PLA, chitosan, and CuNPs mitigated the inflammatory processes and promoted tissue regeneration more effectively. However, this study identified potential toxicity related to copper ions, emphasizing the need for careful optimization of CuNP concentrations. These findings suggest that PLA/Ch-CuNPs could serve as a potent, cost-effective wound dressing with broad-spectrum antibacterial properties, addressing the challenge of antibiotic-resistant infections and enhancing wound healing outcomes. [ABSTRACT FROM AUTHOR]

Skin wounds, due to their high vulnerability to infections, represent a significant public health issue. These wounds are not only disabling but also entail costly treatments and slow recovery. Consequently, it is crucial to implement new treatments based on bioactive and natural antimicrobial compounds utilizing fibers, polymers, hydrocolloids, and hydrogels to control potential infections and promote wound healing. This study aimed to develop a biocomposite with antimicrobial activity for the treatment of skin wounds, using sodium alginate, bamboo fiber, and a natural antimicrobial as ingredients. The physico-mechanical properties (Young's modulus, tensile strength, elongation at break, moisture absorption, and water vapor permeability) and antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Staphylococcus hominis were determined. The results demonstrated that the designed biocomposite possesses adequate physico-mechanical properties, such as flexibility, strength, and water absorption capacity, in addition to exhibiting antibacterial activity, making it suitable to be used as a dressing in wound treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion Open skin wounds increase the risk of infections and can compromise health. Therefore, applying medications to promote healing at the injury site is crucial. In practice, direct drug delivery is often difficult to maintain for a long time due to rapid absorption or wiping off, which reduces the efficiency of wound healing. Consequently, the development of bioactive materials with both antibacterial and wound‐healing properties is highly desirable.This study synthesized liposomes loaded with glycyrrhizic acid (GA) and asiaticoside (AS) by film dispersion‐ultrasonication method, which were then incorporated into a GelMA solution and cross‐linked by ultraviolet light to form a bioactive composite hydrogel for wound dressings.This hydrogel is conducive to the transport of nutrients and gas exchange. Compared with GelMA hydrogel (swelling rate 69.8% ± 5.7%), the swelling rate of GelMA/Lip@GA@AS is lower, at 52.1% ± 1.0%. GelMA/Lip@GA@AS also has better compression and rheological properties, and the in vitro biodegradability is not significantly different from that of the collagenase‐treated group. In addition, the hydrogel polymer has a stable drug release rate, good biocompatibility, and an angiogenic promoting effect. In vitro experiments prove that, at concentrations of 0.5, 1, 2, and 3 mg/mL, GelMA/Lip@GA@AS can inhibit the growth of Staphylococcus aureus.We synthesized GelMA/Lip@GA@AS hydrogel and found it possesses advantageous mechanical properties, rheology, and biodegradability. Experimental results in vitro showed that the bioactive hydrogel could efficiently release drugs, exhibit biocompatibility, and enhance angiogenesis and antimicrobial effects. These results suggest the promising application of GelMA/Lip@GA@AS hydrogel in wound‐dressing materials. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effects of topical naltrexone on wound healing in freshwater fish. ANIMALS 25 blackbelt cichlids (Vieja maculicauda). METHODS A randomized, controlled, experimental trial was performed, with each individual serving as its own control. Bilateral 6-mm periepaxial cutaneous wounds were created in the body-wall skin of each fish under anesthesia. Three treatment groups were as follows: topical 0.04% naltrexone in administration vehicle (iLEX ointment; iLEX Health Products) at day 0 only (n = 10), topical 0.04% naltrexone in iLEX every 72 to 96 hours (n = 10), or iLEX only every 72 to 96 hours (n = 5) for 10 total treatments. The contralateral wound was left untreated as a control. Fish were maintained in a common enclosure at 24.7 to 25.4 °C for 35 days. Macroscopic wound assessment and image collection were performed every 72 to 96 hours. On day 35, fish were humanely euthanized, and skin samples were collected for histopathology. RESULTS Time to complete visual resolution of wound healing was faster (P = .002) in wounds treated every 72 to 96 hours with topical 0.04% naltrexone in iLEX (day 19.4) compared to untreated wounds (day 23.3). An interaction between treatment and day was observed (P = .002), with fish treated with 0.04% naltrexone in iLEX every 72 to 96 hours having reduced (P < .05) wound area compared to both controls and fish treated with topical 0.04% naltrexone in iLEX once. No significant differences were noted in histologic sections of wound sites examined at day 35. CLINICAL RELEVANCE Fish improved earlier postsurgery and time to complete wound resolution was faster in wounds treated with topical 0.04% naltrexone in iLEX every 72 to 96 hours. [ABSTRACT FROM AUTHOR]

Abnormal healing following skin injury, such as slow healing and scar formation, can significantly affect an individual's life. Complex treatment methods and cumbersome instruments have reduced the efficacy of treating such diseases. In this study, a novel biocompatible liquid metal (LM) composite wound dressing (LGPU) is designed by synthesizing polyurea polyurethane (PU) and blending it with LM modified with glutathione (GSH), a bioactive three‐peptide compound. The effects of external electrical stimulation (ES) on wound‐induced hair follicle neogenesis are explored. The dressings exhibited a few important properties, including conductivity, high stretchability, recyclability, and, most importantly, excellent self‐healing capacity, owing to the liquid nature of the LM fillers and the highly dynamic characteristics of hydrogen bonds. Furthermore, the combination therapy with LGPU and ES promoted fibroblast migration and accelerated wound healing. The wounds treated with the combination therapy fully healed in nine days, while the wounds in the blank group are still in a scabbing state. Remarkably, this treatment method can activate the regeneration and healthy growth of hair follicles at the site of injury, which is beneficial for reducing wound scarring. Collectively, this innovative therapy provides a facile strategy to accelerate skin wound healing and achieve scar‐free repair. [ABSTRACT FROM AUTHOR]

Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using in-silico analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 in vitro. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely via its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, trans -dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing. [Display omitted] • FSTL1 is a promigratory protein crucial for keratinocyte migration that facilitates cutaneous wound healing. • Post-translational modification (PTM) of FSTL1 determines the tissue specific functionality of the protein. • A novel phosphorylation PTM at S165 was found to be critical for its pro-migratory function in vitro • S165 phosphorylation does not affect its secretion or proliferative effect on keratinocytes. [ABSTRACT FROM AUTHOR]

The skin injuries pose a substantial public health challenge, not only due to their physical trauma but also the accompanying pain and complexities in wound healing. In the current research, Inula helenium extract and lidocaine were loaded into electrospun PVA/calcium alginate nanofibers to promote skin wounds healing and alleviate the resulting pain. Various in vitro experiments were utilized to characterize these dressings. Wound healing potential of these constructs and their analgesic effects were studied in a rat model of skin wounds. Our developed scaffolds released the loaded drugs in a slow manner and showed antioxidative and anti-inflammatory activities. Fiber size measurement showed that drug-loaded and drug-free scaffolds had around 418.025 ± 140.11 nm and 505.51 ± 93.29 nm mean fiber size, respectively. Bacterial penetration assay confirmed that drug-loaded scaffolds reduced bacterial infiltration through the matrices. Wound healing study showed that on day 14th, the dressings loaded with inula helenium extract and lidocaine could close the wounds up to 91.26 ± 5.93%. In addition, these scaffolds significantly reduced the animals pain sensitivity. ELISA assay results implied that these dressings modulated inflammation and reduced tissue's oxidative stress. [ABSTRACT FROM AUTHOR]

Designing a wound dressing with controlled uptake, antibacterial, and proper biocompatibility is crucial for the appropriate wound healing process. In this study, alginate/tetracycline (Alg/TC) beads were produced and embedded into chitosan/pluronic/agarose semi-interpenetrating polymer network hydrogel, which serves as a potential biocompatible dressing for treating skin wounds. The effect of pluronic content on the porosity, swelling, mechanical characteristics, and degradation of the hydrogel was investigated. Furthermore, the impact of Alg beads on TC release was subsequently examined. In the absence of Alg beads, faster release was observed. However, after incorporating beads into the hydrogels, the release was sustained. Particularly, the hydrogel containing Alg beads exhibited a nearly linear release, reaching 74% after 2 days in acidic media. The antimicrobial activity and biocompatibility of the hydrogel were also evaluated to assess the capability of the TC-loaded hydrogels for wound dressing applications. The hydrogel demonstrated efficient antibacterial features against Gram-positive and Gram-negative bacteria. Additionally, the sample behavior was evaluated against exposure to yeast. Furthermore, based on biocompatibility studies using HFF2 cells, the TC-loaded hydrogel exhibited remarkable biocompatibility. Overall, this novel composite hydrogel shows remarkable biocompatibility and antibacterial activities which can be used as a great potential wound dressing to prevent wound infections due to its effective inhibition of bacterial growth. [ABSTRACT FROM AUTHOR]

Background and Objectives: Muscle loss is a known complication of ICU admission. The aim of the study was to investigate the effect of neuromuscular functional magnetic stimulation (FMS) on quadriceps muscle thickness in critically ill patients. Materials and Methods: Among ICU patients one quadriceps was randomized to FMS (Tesla Stym, Iskra Medical, Ljubljana, Slovenia) stimulation and the other to control care. Quadriceps thickness was measured by ultrasound (US) in transversal and longitudinal planes at enrolment, Days 3–5, and Days 9–12. The trial stopped early following an interim analysis comparing muscle thickness differences between groups using repeated measures ANOVA. Results: Of 18 patients randomized, 2 died before completing the trial. The final analysis reported included 16 patients (female 38%, age 68 ± 10 years, SOFA 10.8 ± 2.7). Three mild skin thermal injuries were noted initially, which were later avoided with proper positioning of FMS probe. Primary outcome comparison showed that quadriceps thickness in transversal and longitudinal planes decreased in the non-stimulated legs and, but it did not change in FMS legs (−4.1 mm (95%CI: −9.4 to −0.6) vs. −0.7 mm (95%CI: −4.1 to −0.7) (p = 0.03) and −4.4 mm (95%CI: −8.9 to −1.1) vs. −1.5 mm (95%CI: −2.6 to −2.2) (p = 0.02), respectively) (ANOVA difference between groups p = 0.036 and 0.01, respectively). Conclusions: In the critically ill, neuromuscular FMS is feasible and safe with precautions applied to avoid possible skin thermal injury. FMS decreases the loss of quadriceps muscle thickness. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) remains an urgent and formidable challenge to global public health. Developing new medicines or alternative therapies to address AMR is imperative. Herein, we rationally designed and synthesized a series of Au(I)‐based aggregation‐induced emission luminogens (AIEgens) to combat drug‐resistant bacterial infections. Through systematic screening, we identified an optimal AIEgen, called complex 5, which can rapidly discriminate between gram‐positive (G+) and gram‐negative bacteria (G−) bacteria, and exert robust and broad‐spectrum antimicrobial potency against diverse drug‐resistant bacterial strains, including those intractable to treat in clinic. Furthermore, extensive testing against a variety of clinical drug‐resistant isolates, coupled with the successful treatment of methicillin‐resistant Staphylococcus aureus‐infected skin wounds unequivocally validates the high efficiency and broad‐spectrum activity of complex 5. Therefore, complex 5 emerges as a promising candidate for combating drug‐resistant bacterial infections in clinic, and this work provides inspiration for developing new solutions to address the escalating global challenge of AMR. [ABSTRACT FROM AUTHOR]

The development of new wound dressings made from biomaterials, which offer a better cost–benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%–4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro‐inflammatory cytokine (IL‐1 α and TNF‐α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro‐inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans. [ABSTRACT FROM AUTHOR]

In engineering, DIC is a widely used measurement technique. Its major advantage is that it provides real-time results (displacements, accelerations, stresses, strains, deformations) of the surface under examination relatively quickly and without contact. However, its application in medicine, biomechanics, and the field of criminalistics is novel. The present research focuses mainly on the frontier areas of forensics and medicine. The research aims to define the test boundary conditions and preparatory activities to measure the surface of the animal and then human skin. Injuries caused by low-energy ballistic bullets, blunt-force trauma, and cuts and punctures caused by knives and/or blades will be investigated. The present research focuses on puncture injuries in animal skin. The main challenge is to create a speckle pattern on the surface that can track deformation well. The research is about developing and validating this. The GOM ARAMIS measurement system was applied for the measurements. This paper demonstrates that a suitable preparation, painting procedure, and measurement setup has been established to measure the above effects, i.e., to identify displacements and deformations of up to tenths of a millimeter with sufficient accuracy. The evaluation of the results will also show that this method could be used in forensic applications, the automotive industry, medical orthopedics, and the textile industry. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) is a promising complement to tissue repair and regenerative medicine approaches. CAP has therapeutic potential in infected cutaneous wounds by mechanisms which remain enigmatic. Here, CAP is shown to activate phagocyte NADPH oxidase complex NOX2. CAP induced increased intracellular reactive oxygen species, alleviated by NOX2 inhibitors. Genetic and pharmacological inhibitions of NOX2 in macrophages and bioengineered skin infected with Staphylococcus aureus and treated with CAP reduced intracellular oxidants and increased bacterial survival. CAP triggered Rac activation and phosphorylation of p40phox and p47phox required for NOX2 assembly and activity. Furthermore, CAP induced collagen I expression by fibroblasts. Infection and healing kinetics showed that murine skin wounds infected with S. aureus and treated with CAP are characterized by decreased bacterial burden, increased length of neoepidermis and extracellular matrix formation. Collectively, our findings identify mechanisms triggered by CAP that subdue infection and result in enhanced repair following skin injury. [ABSTRACT FROM AUTHOR]

Background Keloids are excessive formations of scar tissue that develop at the site of a skin injury. Due to their invasive nature, they have a negative impact on the skin's appearance and are prone to recurrence, making them a challenging condition to treat with regard to skin aesthetics. Objectives The objective of this article was to compare the long-term effects of dermatologic trephination with nonsurgical treatments for scars and evaluate the clinical value of the treatments. Methods A retrospective analysis was conducted of 48 patients who received keloid treatment in the Department of Dermatology and Department of Thoracic Surgery at our hospital from January 2021 to October 2023. Twenty-four patients received dermatologic trephination, and 24 patients received nonsurgical treatment. Outcome measures included scar appearance, scar healing time, pain and itching levels, and patient satisfaction. Results The healing time of patients receiving dermatologic trephination was significantly shorter than that of patients in the nonsurgical group. The degree of itching in patients undergoing dermatologic trephination was significantly lower than that of patients in the nonsurgical group. The satisfaction of patients who received dermatologic trephination was significantly higher than that of patients in the nonsurgical group. Conclusions In this study we demonstrated that trephination achieves better long-term results in keloid revision, including improved keloid appearance, itching symptoms, and patient satisfaction. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]

Short sequences of amino acids called peptides have a wide range of biological functions and the potential to treat a number of diseases. Bioactive peptides can be derived from different sources, including marine organisms, and synthetic design, making them versatile candidates for production of therapeutic agents. Their therapeutic effects span across areas such as antimicrobial activity, cells proliferation and migration, synthesis of collagen, and more. This current review explores the fascinating realm of bioactive peptides as promising therapeutic agents for skin wound healing. This review focuses on the multifaceted biological effects of specific peptides, shedding light on their potential to revolutionize the field of dermatology and regenerative medicine. It delves into how these peptides stimulate collagen synthesis, inhibit inflammation, and accelerate tissue regeneration, ultimately contributing to the effective repair of skin wounds. The findings underscore the significant role several types of bioactive peptides can play in enhancing wound healing processes and offer promising insights for improving the quality of life for individuals with skin injuries and dermatological conditions. The versatility of peptides allows for the development of tailored treatments catering to specific wound types and patient needs. As continuing to delve deeper into the realm of bioactive peptides, there is immense potential for further exploration and innovation. Future endeavors may involve the optimization of peptide formulations, elucidation of underlying molecular and cellular mechanisms. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by protozoan parasites from different species of leishmania. The disease is transmitted by female sandflies that carry these parasites. In this study, datasets on leishmaniasis published in the GEO database were analyzed and summarized. The analysis in all three datasets (GSE43880, GSE55664, and GSE63931) used in this study has been performed on the skin wounds of patients infected with a clinical form of leishmania (Leishmania braziliensis), and biopsies have been taken from them. To identify differentially expressed genes (DEGs) between leishmaniasis patients and controls, the robust rank aggregation (RRA) procedure was applied. We performed gene functional annotation and protein-protein interaction (PPI) network analysis to demonstrate the putative functionalities of the DEGs. The study utilized Molecular Complex Detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to detect molecular complexes within the protein-protein interaction (PPI) network and conduct analyses on the identified functional modules. The CytoHubba plugin's results were paired with RRA analysis to determine the hub genes. Finally, the interaction between miRNAs and hub genes was predicted. Based on the RRA integrated analysis, 407 DEGs were identified (263 up-regulated genes and 144 down-regulated genes). The top three modules were listed after creating the PPI network via the MCODE plug. Seven hub genes were found using the CytoHubba app and RRA: CXCL10, GBP1, GNLY, GZMA, GZMB, NKG7, and UBD. According to our enrichment analysis, these functional modules were primarily associated with immune pathways, cytokine activity/signaling pathways, and inflammation pathways. However, a UBD hub gene is interestingly involved in the ubiquitination pathways of pathogenesis. The mirNet database predicted the hub gene's interaction with miRNAs, and results revealed that several miRNAs, including mir-146a-5p, crucial in fighting pathogenesis. The key hub genes discovered in this work may be considered as potential biomarkers in diagnosis, development of agonists/antagonist, novel vaccine design, and will greatly contribute to clinical studies in the future. [ABSTRACT FROM AUTHOR]

A burn is a type of injury to the skin or other tissues caused by heat, chemicals, electricity, sunlight, or radiation. Burn injuries have been proven to have the potential for long-term detrimental effects on the human body. The conventional therapeutic approaches are not able to effectively and easily heal these burn wounds completely. The main potential drawbacks of these treatments include hypertrophic scarring, contracture, infection, necrosis, allergic reactions, prolonged healing times, and unsatisfactory cosmetic results. The existence of these drawbacks and limitations in current treatment approaches necessitates the need to search for and develop better, more efficient therapies. The regenerative potential of microRNAs (miRNAs) and the exosomal miRNAs derived from various cell types, especially stem cells, offer advantages that outweigh traditional burn wound healing treatment procedures. The use of multiple types of stem cells is gaining interest due to their improved healing efficiency for various applications. Stem cells have several key distinguishing characteristics, including the ability to promote more effective and rapid healing of burn wounds, reduced inflammation levels at the wound site, and less scar tissue formation and fibrosis. In this review, we have discussed the stages of wound healing, the role of exosomes and miRNAs in improving thermal-induced wounds, and the impact of miRNAs in preventing the formation of hypertrophic scars. Research studies, pre-clinical and clinical, on the use of different cell-derived exosomal miRNAs and miRNAs for the treatment of thermal burns have been documented from the year 2000 up to the current time. Studies show that the use of different cell-derived exosomal miRNAs and miRNAs can improve the healing of burn wounds. The migration of exosomal miRNAs to the site of a wound leads to inhibition of apoptosis, induction of autophagy, re-epithelialization, granulation, regeneration of skin appendages, and angiogenesis. In conclusion, this study underscores the importance of integrating miRNA and exosome research into treatment strategies for burn injuries, paving the way for novel therapeutic approaches that could significantly improve patient outcomes and recovery times. [ABSTRACT FROM AUTHOR]

The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced skin injury is a significant adverse reaction to radiotherapy. However, there is a lack of effective prevention and treatment methods for this complication. Ferulic acid (FA) has been identified as an effective anti-radiation agent. Conventional administrations of FA limit the reaching of it on skin. We aimed to develop a novel FA hydrogel to facilitate the use of FA in radiation-induced skin injury. Methods: We cross-linked carbomer 940, a commonly used adjuvant, with FA at concentrations of 5%, 10%, and 15%. Sweep source optical coherence tomography system, a novel skin structure evaluation method, was applied to investigate the influence of FA on radiation-induced skin injury. Calcein-AM/PI staining, CCK8 assay, hemolysis test and scratch test were performed to investigate the biocompatibility of FA hydrogel. The reducibility of DPPH and ABTS radicals by FA hydrogel was also performed. HE staining, Masson staining, laser Doppler blood flow monitor, and OCT imaging system are used to evaluate the degree of skin tissue damage. Potential differentially expressed genes were screened via transcriptome analysis. Results: Good biocompatibility and in vitro antioxidant ability of the FA hydrogels were observed. 10% FA hydrogel presented a better mechanical stability than 5% and 15% FA hydrogel. All three concentrations of FA remarkably promoted the recovery of radiation-induced skin injury by reducing inflammation, oxidative conidiation, skin blood flow, and accelerating skin tissue reconstruction, collagen deposition. FA hydrogel greatly inhibiting the levels of NLRP3, caspase-1, IL-18, pro-IL-1β and IL-1β in vivo and vitro levels through restraining the activation of NLRP3 inflammasome. Transcriptome analysis indicated that FA might regulate wound healing via targeting immune response, inflammatory response, cell migration, angiogenesis, hypoxia response, and cell matrix adhesion. Conclusions: These findings suggest that the novel FA hydrogel is a promising therapeutic method for the prevention and treatment of radiation-induced skin injury patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the use of cyanoacrylate-based adhesives and their effects on the closure of surgical wounds. Different commercial and surgically indicated cyanoacrylate molecules were compared with each other and with conventional suture. The materials were evaluated for polarization time, scar resistance, inflammatory index, and healing. Promising results were observed in surgical wounds treated with adhesive compared to suture thread. Cyanoacrylate-based adhesives are widely used in wound closure, providing good cosmetic results and little discomfort. However, reports in the literature are found about negative effects that include the release of cytotoxic chemicals during biodegradation. In this study, we sought to evaluate and compare the effectiveness of four cyanoacrylate-based adhesives on the closure of skin incisions in Rattus norvegicus. The animals (n = 140) were divided into five groups of 28 animals each according to the wound closure technique: G1 and G2 (n-2-ethyl-cyanoacrylate); G3 (n-2-butyl-cyanoacrylate); G4 (n-2-octyl-cyanoacrylate); and G5 (5 nylon stitches). Midline incisions measuring 5.0 cm in length were created and closed using the different materials evaluated, and on D3, D7, D14, and D21, tensiometric and histopathological analyses were performed. Shorter wound closure and adhesion times were observed in G4 animals. At D3 and D7, G5 presented greater tensiometric resistance in the animals of G5, with a decrease in D14 and D21 compared to the other groups. On the other hand, the wounds of G3 and G4 were more resistant in D14 and D21, reaching maximum resistance values. Polymorphonuclear and mononuclear cells are more prevalent and more granulation tissue was observed in G5. The deposition of type III collagen was more evident in G5, whilst there was no difference in the amount of type I collagen in any of the groups treated with cyanoacrylate adhesives. Larger areas stained positive for VEGF-α in G2 and smaller areas in G4, with peaks at D7 and D14. In general, cyanoacrylate adhesives cause less intense inflammatory reactions, resulting in shorter healing times when compared to nylon sutures. [ABSTRACT FROM AUTHOR]

The poor healing of diabetic wounds is characterized by prolonged inflammation and decreased collagen deposition. Diabetic patients exhibit changes in the plasma concentrations of pro-inflammatory cytokines, and the role of specific dressings may have an impact on healing. This study aims to evaluate the effects of a combined treatment comprising a bacterial cellulose dressing and melatonin application on the regulation and expression of inflammatory cytokines, VEGF, PCNA, and collagen in the healing of cutaneous wounds of diabetic rats. Pro-inflammatory cytokines, including IL-6, TNF-α, and VEGF, along with PCNA and type I and III collagen, were evaluated after 14 days. Immunohistochemistry showed decreased levels of IL-6, TNF-α, and VEGF, along with an increased expression of PCNA and type I collagen, in the groups treated exclusively with melatonin and bacterial cellulose associated with melatonin compared to the control and the commercial healing agent. It was concluded that treating the skin lesions of diabetic animals supplemented with melatonin using a bacterial cellulose-based dressing has positive effects in regulating the expression of inflammatory cytokines, vascular endothelial growth factor, and collagen, showing that this association could be a viable therapy approach in wound healing. [ABSTRACT FROM AUTHOR]

Nowadays, there has been an increasing research interest into N-halamine compounds due to their wide antimicrobial properties and no drug resistance. Most of the research mainly focuses on small molecular N-halamines, while few studies are on macromolecule N-halamines. In this work, antibacterial N-halamine polymer materials based on proteins (GS-Cl) were synthesized with an antibacterial component of oxidative chlorine, a support component of a gelatin sponge. After carrying out systematic characterization, the GS-Cls exhibited well-defined porous morphology and had a high efficiency in the killing of Gram-positive bacteria (E. coli) and Gram-negative bacteria (S. aureus). The loading of oxidative chlorine (Cl+%) could be controlled by changing the NaClO concentrations and chlorination times. The biocompatibility was confirmed as well. In vivo experiments suggested that the GS-Cl sample could effectively promote the healing of skin wounds in mice E. coli and S. aureus infection models. These studies show that proteins can be chlorinated and endowed with antimicrobial properties, which has great application potential in the treatment of bacteria-infected wounds. [ABSTRACT FROM AUTHOR]

Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized pathological function of S100A9 overexpression in wounds with impaired healing that directly affects ECM functions in fibroblasts. S100A9 was analyzed in two different mouse models mimicking the features of the two most prominent types of non-healing wounds in humans. Db/db mice were used as a model for diabetes-associated impaired wound healing. Iron-overloaded mice were used to mimic the conditions of impaired wound healing in chronic venous leg ulcers. The skin wounds of both mouse models are characterized by delayed wound closure, high and sustained expression of pro-inflammatory mediators and a substantially decreased ECM deposition, all together the hallmarks of non-healing wounds in humans. The wounds of both mouse models also present a solid and prolonged expression of S100A8 and S100A9 that coincides with a compromised ECM deposition and that was confirmed in chronic wounds in humans. Mechanistically, we reveal that S100A9 directly affects ECM deposition by shifting the balance of expression of ECM proteins and ECM degrading enzymes in fibroblasts via toll-like-receptor 4-dependent signaling. Consequently, blocking S100A9 during delayed wound healing in db/db mice restores fibroblast ECM functions eliciting increased matrix deposition. Our data indicate that the dysregulation of S100A9 directly contributes to a compromised ECM deposition in chronic wounds and further suggests S100A9 as a promising therapeutic target to improve tissue repair in chronic wounds. [ABSTRACT FROM AUTHOR]

Skin-resident regulatory T cells (Tregs) play an irreplaceable role in orchestrating cutaneous immune homeostasis and repair, including the promotion of hair regeneration via the Notch signaling ligand Jagged-1 (Jag1). While skin Tregs are indispensable for facilitating tissue repair post-wounding, it remains unknown if Jag1-expressing skin Tregs impact wound healing. Using a tamoxifen inducible Foxp3creERT2Jag1fl/fl model, we show that loss of functional Jag1 in Tregs significantly delays the rate of full-thickness wound closure. Unlike in hair regeneration, skin Tregs do not utilize Jag1 to impact epithelial stem cells during wound healing. Instead, mice with Treg-specific Jag1 ablation exhibit a significant reduction in Ly6G + neutrophil accumulation at the wound site. However, during both homeostasis and wound healing, the loss of Jag1 in Tregs does not impact the overall abundance or activation profile of immune cell targets in the skin, such as CD4+ and CD8+ T cells, or pro-inflammatory macrophages. This collectively suggests that skin Tregs may utilize Jag1-Notch signalling to co-ordinate innate cell recruitment under conditions of injury but not homeostasis. Overall, our study demonstrates the importance of Jag1 expression in Tregs to facilitate adequate wound repair in the skin. [ABSTRACT FROM AUTHOR]

Background: Diabetic skin wound is a complex problem due to the disruption of normal repairing program and lack of effective remedy. Lucilia sericata larvae (maggot) is a folk method to treat chronic skin wound, while its therapeutic effects on that caused by diabetic remains unknown. Objective: This study aims to investigate the therapeutic effects of maggot extract (M.E.) on diabetic skin wound and its molecular mechanism by establishing the skin wound model of diabetic Sprague Dawley (SD) rats. Methods: Diabetic model was established by injecting intraperitoneally streptozotocin in SD rats under specific pathogen-free (SPF) conditions. The rat fasting blood glucose values were ≧16.7 mmol/L 72 hours after intraperitoneal streptozotocin (60mg/kg body weight) injection. The rats were divided into five groups (n = 10/group): normal group: normal SD rats without any treatment, diabetic blank group: the diabetic rats without any treatment, Vaseline group: the diabetic rats dressed with Vaseline, recombinant human epidermal-growth-factor (rhEGF) group: the diabetic rats dressed with a mixture of Vaseline and 200 μg/g rhEGF, M.E. group: the diabetic rats dressed with a mixture of Vaseline and 150 μg/ml maggot extract. The round open wounds (1.0 cm in diameter) down to the muscle fascia were made on both sides of rat dorsa by removing the skin layer (epidermis and dermis) and were daily photographed for calculating their healing rates. Hematoxylin-eosin (HE) and Masson's trichrome staining were performed on skin wound sections to analyze re-epithelialization and granulation tissue formation. Immunohistochemical (IHC), immunofluorescent (IF) stainings and Western blotting were conducted to analyze the statuses of STAT3 signaling. Results: The average wound healing rates on the 14th day were 91.7% in the normal, 79.6% in M.E., 71% in rhEGF, 55.1% in vaseline and 43.3% in the diabetes blank group. Morphological staining showed more active granulation tissue formation, re-epithelialization and neovascularization in M.E.-group than those in the blank and the vaseline-treated groups. Decreased p-STAT3 nuclear tranlocation and down-regulated Bcl-2, CyclinD1 and vascular endothelial growth factor (VEGF) expression were evidenced in the diabetic rats, which could be improved by rhEGF and especially M.E. Conclusion: Maggot extract would be an alternative and/or adjuvant candidate for the better management of diabetic skin wounds because of its activity in enhancing STAT3 activation. [ABSTRACT FROM AUTHOR]

Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo's protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action. [ABSTRACT FROM AUTHOR]