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Introduction: Post-burn hypertrophic scars are an important cause of physical discomfort, limitation of movements, psychological disorders, low self-esteem and reduced quality of life. Treatment for this condition is complex and involves several options. Microneedling, also known as minimally invasive percutaneous collagen induction, is an affordable minimally invasive option that can be combined with other treatments, including ablative ones. Objective: The goal of this study was to present our microneedling approach for the treatment of hypertrophic scars after burns. Method: A prospective study of 15 patients with post-burn hypertrophic scars was conducted between October 2016 and June 2022. All patients were treated with microneedling and drug delivery of triamcinolone. Scars were evaluated using Vancouver Scar Scale (VSS), Burn Scar Assessment Scale (BSAS) and angle measurement for amplitude of movement evaluation of joints. Results: A significant improvement in the VSS score was obtained after microneedling (8.8 ± 0.44 to 4.1 ± 0.98; p = 0.012), especially in the acute group (less than 1 year after burns): 9.3 ± 0.49 to 3.5 ± 1.36; p = 0.041. There was a significant and progressive improvement of the scars throughout the treatment sessions in all criteria evaluated and in the ranges of joint movement (p = 0.012). Conclusion: Our microneedling protocol promoted a significant improvement of post-burn scars, especially in acute hypertrophic scars, and in the amplitude of joint motion. Sequential treatments provided progressive improvement. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Introduction and purpose Botulinum toxin has been used in medicine since the 1970s, although many years earlier it was known only as a biological weapon. Originally, it was used in medicine to treat strabismus in children. Over time, it has been used in the treatment of neurological disorders, excessive sweating of the armpits, wrinkles, and bladder disorders. In recent years, botulinum toxin has also begun to be used in wound healing. The paralyzing effect of botulinum toxin on the muscles within the wound eliminates micro-injuries caused by tension in these muscles. The aim of the article is to summarize information on the effects of botulinum toxin on the wound, its impact on inflammation, and the type of scar formation. Materials and methods The literature included in the PubMed databases is searched through the words such as botulinum toxin, wounds, and scars. Description of the state of knowledge: The literature review shows the breadth of the issue. Scientific studies showing the effect of using botulinum toxin on wounds emphasize its beneficial effects. However, it should be remembered that wound healing has a complex, dynamic course supported by numerous cellular processes that must be closely coordinated to effectively repair damaged tissues. Determinants influencing the course of wound healing include both local and systemic factors. Important factors influencing the process of proper wound healing are specialized wound preparation, pharmacotherapy, and other aspects of therapeutic intervention. Conclusions The range of applications of botulinum toxin is constantly expanding. In addition to reducing muscle tension within the wound, it also inhibits the production of inflammatory transmitters, limiting its development, and also reduces the development of microcirculation by preventing the development of vessels in hypertrophic scars. [ABSTRACT FROM AUTHOR]

Background: Epidermal remodeling and hypertrophy are hallmarks of skin fibrotic disorders, and keratinocyte to mesenchymal (EMT)-like transformations drive epidermis alteration in skin fibrosis such as keloids and hypertrophic scars (HTS). While phosphodiesterase 4 (PDE4) inhibitors have shown effectiveness in various fibrotic disorders, their role in skin fibrosis is not fully understood. This study aimed to explore the specific role of PDE4B in epidermal remodeling and hypertrophy seen in skin fibrosis. Methods: In vitro experiments examined the effects of inhibiting PDE4A-D (with Roflumilast) or PDE4B (with siRNA) on TGFβ1-induced EMT differentiation and dedifferentiation in human 3D epidermis. In vivo studies investigated the impact of PDE4 inhibition on HOCl-induced skin fibrosis and epidermal hypertrophy in mice, employing both preventive and therapeutic approaches. Results: The study found increased levels of PDE4B (mRNA, protein) in keloids > HTS compared to healthy epidermis, as well as in TGFβ-stimulated 3D epidermis. Keloids and HTS epidermis exhibited elevated levels of collagen Iα1, fibronectin, αSMA, N-cadherin, and NOX4 mRNA, along with decreased levels of E-cadherin and ZO-1, confirming an EMT process. Inhibition of both PDE4A-D and PDE4B prevented TGFβ1-induced Smad3 and ERK1/2 phosphorylation and mesenchymal differentiation in vitro. PDE4A-D inhibition also promoted mesenchymal dedifferentiation and reduced TGFβ1-induced ROS and keratinocyte senescence by rescuing PPM1A, a Smad3 phosphatase. In vivo, PDE4 inhibition mitigated HOCl-induced epidermal hypertrophy in mice in both preventive and therapeutic settings. Conclusions: Overall, the study supports the potential of PDE4 inhibitors, particularly PDE4B, in treating skin fibrosis, including keloids and HTS, shedding light on their functional role in this condition. [ABSTRACT FROM AUTHOR]

A pressure of approximately 15–25 mmHg is used for effective compression therapy to prevent and treat hypertrophic scar formation in patients with burns. However, conventional facial compression garments present challenges owing to inadequate pressure distribution in curved areas such as the cheeks, around the mouth, and the slope of the nose. This study aimed to evaluate the utility of a custom-made 3D compression mask equipped with pressure sensors to treat facial burn scars. This single-blinded, prospective randomized controlled trial was conducted between May and October 2023, involving 48 burn scars in 12 inpatients with facial burns. We created the custom-made 3D compression mask equipped with pressure sensors, inner lined with biocompatible silicon, and a harness system using 3D printing technology, which can continuously monitor whether an appropriate pressure of 15–25 mmHg maintains. The biological scar properties, Vancouver Scar Scale (VSS), and Patient and Observer Scar Assessment Scale (POSAS) scores in patients with facial burns were assessed before applying the compression mask and garment and at 4 and 12 weeks after application. Pre-application assessment of biological scar properties, VSS, and POSAS revealed no statistically significant differences between the 3D mask and control groups (p > 0.05 for all). Throughout the 12-week application, skin hydration and scar thickness significantly increased (p < 0.001) and reduced (p = 0.010), respectively , in the 3D mask group compared to the control group. Additionally, significant improvements in scar pliability (p = 0.004) and height (p = 0.009) of VSS, itching (p = 0.047), scar stiffness (p = 0.001), thickness (p = 0.011), and irregularity (p < 0.001) of POSAS-patient component, and scar thickness (p = 0.001), pliability (p = 0.012), and surface area (p = 0.027) of the POSAS-observer component were observed in 3D mask group throughout the 12-week application compared to the control group. The customized 3D compression mask equipped with pressure sensors significantly improved scar thickness, skin hydration, and various assessment scale parameters throughout the 12-week application. • Customized 3D compression mask maintains a pressure of approximately 15–25 mmHg. • Real-time pressure feedback aids scar management. • More improved facial scar thickness and skin hydration in the 3D mask group. • 3D compression masks were more effective than conventional compression garment. [ABSTRACT FROM AUTHOR]

Paediatric patients with hypertrophic burn scars benefit from laser treatment, but this treatment's effectiveness on burn wounds stratified by specific body region and prior burn wound therapy has not been fully evaluated. We performed a single center retrospective study of pediatric burn patients, treated with fractional CO2, with or without pulse dye, laser between 2018–2022. We identified 99 patients treated with 332 laser sessions. Median age at the time of burn injury was 4.0 years (IQR 1.7, 10.0) and 7.1 years (IQR 3.6, 12.2) at the time of first laser treatment. In the acute setting, 55.2 % were treated with dermal substrate followed by autografting, 29.6 % were treated with dermal substrate alone, and 9.1 % underwent autografting alone. Most body regions showed improvement in modified Vancouver Scar Scale (mVSS) score with laser treatment. mVSS scores improved significantly with treatment to the anterior trunk (−1.18, p = 0.01), arms (−1.14, p = 0.003), and legs (−1.17, p = 0.015). Averaging all body regions, the mVSS components of pigmentation (−0.34, p < 0.001) and vascularity (−0.47, p < 0.001), as well as total score (−0.81, p < 0.001) improved significantly. Knowing the variable effectiveness of laser treatment in pediatric burn scars is useful in counseling patients and families pre-treatment. • Burn regions appears to have different response to laser therapy based on VSS. • Anterior trunk & extremity burn scars improved significantly with laser treatment. • Hypertrophic burn scars from flame and scald burns improved with laser treatment. • Burn scar pigmentation and vascularity improved significantly with laser treatment. • Response to laser therapy differs based on prior burn wound management. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Archives of Dermatological Research that discusses a cross-sectional analysis of the All of Us database to understand hypertrophic scars (HTS) in underrepresented groups. The study found that HTS patients were more likely to be Black, Asian, and female, while patients over 65, without health insurance, with lower education, and low income had lower odds of HTS. Patients with HTS also had a higher odds of various comorbidities. The letter includes two tables that provide information on the prevalence of certain characteristics and comorbidities in individuals with HTS compared to those without HTS. The study highlights the importance of early identification of at-risk populations and the need for improved accessibility and affordability of HTS diagnosis and treatment. [Extracted from the article]

This study examines a rare case of frostbite on the hands caused by liquid nitrogen, focusing on the scar maturation process. Frostbite is typically less prone to abnormal scarring compared to burns, and this report contrasts the differences in scar maturation between the two. A 31-year-old male hospital employee sustained first- to second-degree frostbite on his gloved hands from a 20-s exposure to liquid nitrogen while changing a cylinder. Conservative treatment was applied, and the patient was monitored for 9 months. The deeply affected area took 50 days to epithelialize but healed without hypertrophic scarring. A mild extension contracture was noted in the distal interphalangeal joint of the right index finger, but the skin remained supple and soft. Incidents of liquid nitrogen-induced frostbite are uncommon, with only 14 cases reported in PubMed previously. In frostbite, the wound healing involves a slow replacement of damaged connective tissue, which acts as an internal splint, reducing wound contraction. This contrasts with burns, where rapid connective tissue replacement occurs, often leading to significant wound contraction due to the presence of myofibroblasts in granulation tissue. In the presented case, the slow healing process and minimal wound contraction led to mature scarring without abnormalities, underlining a distinctive healing trajectory in frostbite injuries compared to burns. [ABSTRACT FROM AUTHOR]

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography–tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2ʹ-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis—especially that of type III—thereby reducing the type I/III ratio and improving hypertrophic scarring. [ABSTRACT FROM AUTHOR]

Background: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL. Methodology & principal findings: A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders' meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. "Clinical Cure" was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach. Conclusion: LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future. Author summary: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease caused by the parasite Leishmania spp. Literature review identified inconsistencies in methods and parameters used to evaluate treatment/alternative-interventions resulting in difficulties in comparing new treatment/interventions in clinical trials. In our international consensual study, we adopted the face-to-face nominal group technique and a judgment process to identify domains key to assessment of LCL. Subsequent measures for each domain were used to form a Core Outcome Set (COS). LeishCOM_LCL was developed as an outcome measure instrument (OMI) to capture the COS incorporating existing and newly developed tools. "Clinical Cure" was agreed as the "General Concept" to be captured through five domains. It was agreed that "Signs" domain should capture clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score. "Treatment Efficacy" was assessed by recording percentage change in size of the lesion and re-epithelialization compared to baseline. "Treatment Impact" was reflected through an investigator and the patient visual analogue score and "Clinical Sequelae" rated pigment change, atrophic/hypertrophic scars. Two open-ended questions were included to capture some aspects of "Health-Related Quality of Life". LeishCOM_LCL also records patient demographic details and was validated in a small cohort of patients. [ABSTRACT FROM AUTHOR]

Background Aims Methods Results Conclusions Bleomycin, originally an antitumor drug, was explored as a pathological scar treatment in the mid‐1990s. However, its efficacy and safety profile varies among individuals.This study aimed to assess topical bleomycin's efficacy and safety in treating hypertrophic scars and keloids.We reviewed randomized controlled trials (RCTs) and controlled clinical trials (CCTs) published in English, comparing intralesional bleomycin to placebos or common intralesional scar treatments. Primary outcomes included percentage change in scar improvement, pigmentation, recurrence, atrophy, pain, telangiectasia, ulceration, patient self‐assessment, and observer assessment (>50%).Six trials met the criteria. Bleomycin significantly improved scar reduction compared to triamcinolone (p < 0.05). There was no significant difference in pigmentation (p = 0.05) and recurrence (p = 0.21) compared to other treatments. In terms of safety, bleomycin caused less skin atrophy (p < 0.01) and telangiectasia (p < 0.01) but more pain (p = 0.03) than other treatments.Bleomycin was more effective than TAC, 5‐FU, or TAC combined with 5‐FU for treating keloids and hypertrophic scars with lower skin atrophy and telangiectasia risks. However, it may cause more pain than 5‐FU or TAC. Further comprehensive studies, including RCTs, are required for objective analysis. [ABSTRACT FROM AUTHOR]

Hypertrophic scarring is an aberrant wound-healing response to reestablish dermal integrity after an injury and can cause significant abnormalities in physical, aesthetic, functional, and psychological symptoms, impacting the patient's quality of life. There is currently no gold standard for preventing and treating hypertrophic scars. Therefore, many researchers have attempted to search for antihypertrophic scar agents with greater efficacy and fewer side effects. Natural therapeutics are becoming attractive as potential alternative anti-scarring agents because of their high efficacy, safety, biocompatibility, low cost, and easy accessibility. This review demonstrates various kinds of natural product-based therapeutics, including onion, vitamin E, Gotu kola, green tea, resveratrol, emodin, curcumin, and others, in terms of their mechanisms of action, evidence of efficacy and safety, advantages, and disadvantages when used as anti-scarring agents. We reviewed the literature based on data from in vitro, in vivo, and clinical trials. A total of 23 clinical trials were identified in this review; most clinical trials were ranked as having uncertain results (level of evidence 2b; n = 16). Although these natural products showed beneficial effects in both in vitro and in vivo studies of potential anti-scarring agents, there was limited clinical evidence to support their efficacy due to the limited quality of the studies, with individual flaws including small sample sizes, poor randomization, and blinding, and short follow-up durations. More robust and well-designed clinical trials with large-scale and prolonged follow-up durations are required to clarify the benefits and risks of these agents. [ABSTRACT FROM AUTHOR]

Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis. Consistent with this, we find that SFRP2 is overexpressed in both the dermis and epidermis of human hypertrophic scar tissue and lesional tissue of a mouse scleroderma model. Knockdown of SFRP2 expression in human fibroblasts antagonises proliferation and myofibroblast differentiation, including deposition of type I collagen, suggesting that SFRP2 signalling in fibroblasts may contribute to propagation of fibrosis in hypertrophic scar, as well as in other clinical indications characterised by skin fibrosis. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Nucleoside‐modified messenger RNA (modRNA) holds the potential for facilitating genetic enhancement of stem cells. In this study, modRNA encoding hepatocyte growth factor (modHGF) was used to chemically modify adipose‐derived mesenchymal stem cells (ADSCs) and the effect of modified ADSCs on the activation of hypertrophic scar fibroblasts (HSFs) was evaluated.CCK‐8, wound healing, and transwell assays were utilized to evaluate the viability and migratory potential of modHGF‐engineered ADSCs and their effect on HSF activation. Reverse transcription‐polymerase chain reaction, western blot, and immunofluorescence staining were performed to detect the expression of collagen‐I (Col I), collagen‐III (Col III), alpha‐smooth muscle actin (α‐SMA), matrix metallopeptidase 1 (MMP‐1), and MMP‐3.Transfection of ADSCs with modHGF (HGF‐ADSC) resulted in enhanced production of HGF. Meanwhile, modHGF modification enhanced the viability and migration of ADSCs. Notably, culture media from HGF‐ADSCs exhibited a more potent inhibitory effect on the proliferation and migration of HSFs. In addition, culture media from HGF‐ADSCs inhibited extracellular matrix synthesis of HSFs, as evidenced by reduced expression levels of Col I, Col III, and α‐SMA, while increasing expression of MMP‐1 and MMP‐3. Conversely, neutralization experiments confirmed that these effects could be effectively alleviated by blocking HGF activity.modHGF modification optimizes the inhibitory effect of ADSCs on HSF activation, which provides a promising alternative for preventing and treating hyperplastic scars. [ABSTRACT FROM AUTHOR]

Keloid scars, characterized by abnormal fibroproliferation and excessive extracellular matrix (ECM) production that extends beyond the original wound, often cause pruritus, pain, and hyperpigmentation, significantly impacting the quality of life. Keloid pathogenesis is multifactorial, involving genetic predisposition, immune response dysregulation, and aberrant wound-healing processes. Central molecular pathways such as TGF-β/Smad and JAK/STAT are important in keloid formation by sustaining fibroblast activation and ECM deposition. Conventional treatments, including surgical excision, radiation, laser therapies, and intralesional injections, yield variable success but are limited by high recurrence rates and potential adverse effects. Emerging therapies targeting specific immune pathways, small molecule inhibitors, RNA interference, and mesenchymal stem cells show promise in disrupting the underlying mechanisms of keloid pathogenesis, potentially offering more effective and lasting treatment outcomes. Despite advancements, further research is essential to fully elucidate the precise mechanisms of keloid formation and to develop targeted therapies. Ongoing clinical trials and research efforts are vital for translating these scientific insights into practical treatments that can markedly enhance the quality of life for individuals affected by keloid scars. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is required. However, ex vivo amplification often reduces the desired MSC regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing and contracting extracellular matrix into scar tissue. In contrast, persistent myofibroblasts cause excessive scarring—called fibrosis—that destroys organ function. In this review, we focus on the relevance and molecular mechanisms of myofibroblast activation upon contact with stiff cell culture plastic or recipient scar tissue, such as hypertrophic scars of large skin burns. We discuss cell mechanoperception mechanisms such as integrins and stretch-activated channels, mechanotransduction through the contractile actin cytoskeleton, and conversion of mechanical signals into transcriptional programs via mechanosensitive co-transcription factors, such as YAP, TAZ, and MRTF. We further elaborate how prolonged mechanical stress can create persistent myofibroblast memory by direct mechanotransduction to the nucleus that can evoke lasting epigenetic modifications at the DNA level, such as histone methylation and acetylation. We conclude by projecting how cell culture mechanics can be modulated to generate MSCs, which epigenetically protected against myofibroblast activation and transport desired regeneration potential to the recipient tissue environment in clinical therapies. [ABSTRACT FROM AUTHOR]

The HSP70 co-chaperone BAG3 targets unfolded proteins to degradation via chaperone assisted selective autophagy (CASA), thereby playing pivotal roles in the proteostasis of adult cardiomyocytes (CMs). However, the complex functions of BAG3 for regulating autophagy in cardiac disease are not completely understood. Here, we demonstrate that conditional inactivation of Bag3 in murine CMs leads to age-dependent dysregulation of autophagy, associated with progressive cardiomyopathy. Surprisingly, Bag3 -deficient CMs show increased canonical and non-canonical autophagic flux in the juvenile period when first signs of cardiac dysfunction appear, but reduced autophagy during later stages of the disease. Juvenile Bag3 -deficient CMs are characterized by decreased levels of soluble proteins involved in synchronous contraction of the heart, including the gap junction protein Connexin 43 (CX43). Reiterative administration of chloroquine (CQ), an inhibitor of canonical and non-canonical autophagy, but not inactivation of Atg5 , restores normal concentrations of soluble cardiac proteins in juvenile Bag3 -deficient CMs without an increase of detergent-insoluble proteins, leading to complete recovery of early-stage cardiac dysfunction in Bag3 -deficient mice. We conclude that loss of Bag3 in CMs leads to age-dependent differences in autophagy and cardiac dysfunction. Increased non-canonical autophagic flux in the juvenile period removes soluble proteins involved in cardiac contraction, leading to early-stage cardiomyopathy, which is prevented by reiterative CQ treatment. [Display omitted] • Inactivation of Bag3 in CMs initiates hypertrophic cardiomyopathy in juvenile mice • Juvenile but not late stage Bag3 -deficient CMs show increased autophagic flux • Inactivation of Atg5 does not improve cardiac function in juvenile Bag3 -cKO mice • Treatment with chloroquine normalizes cardiac function in juvenile Bag3 -cKO mice • Human BAG3P209L heart samples show similar changes as in Bag3 -cKO mice [ABSTRACT FROM AUTHOR]

Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS‐targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose‐dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP‐loaded non‐bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes‐associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies. [ABSTRACT FROM AUTHOR]

The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model. Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 µg ‧ cm-2. The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale. The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres. The formation of scars with the best elasticity was exhibited by addition 1.0 µg ‧ cm-2of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research. • The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. • Dermal substitutes based on collagen/chitosan scaffolds. • Collagen-based scaffolds represent great potential for tissue engineering applications, where they serve as carriers for newly formed cells. • Fibroblast growth factor 2 plays an important role during regeneration and reparation of a variety of tissues. • FGF2-STAB® is a 9-point mutant of human FGF2 exhibiting enhanced resistance to elevated temperature and an extended half-life of up to 20 days at 37 °C. [ABSTRACT FROM AUTHOR]

Prominent ears (PEs) are the most frequent congenital external ear deformity, occurring in ∼5% of the population. Although the deformity does not usually cause functional difficulties, it can significantly affect the patient's psychological and social health. The authors aim to present the Welsh experience of pinnaplasty, reviewing our outcomes and complications. A retrospective cross-sectional study was performed of all patients undergoing pinnaplasty in Morriston Hospital, Swansea, Wales. We represent the tertiary plastic surgery referral unit across Wales. We included all patients undergoing pinnaplasty between 2015 and 2022 inclusive. We excluded patients undergoing revision procedures or those who had no follow-up. Over the 7-year period, 236 pinnaplasties were performed and 203 were included in the analysis. Ninety-six percent of cases were performed using a cartilage-sparing approach, which represents the mainstay in our unit. The mean follow-up length for our cases was 12 months. Revision procedures were required in 4% of cases. Three hematomas (1.5%) and one (0.5%) wound dehiscence due to infection were recorded and required a return to the operating room. Suture extrusion was noted in 5% of cases (10 patients); 4.5% (9) cases were affected by either hypertrophic or keloid scarring. Across the United Kingdom, cosmetic procedures have come under scrutiny, namely, because of a difficult economic climate. In the era of tight fiscal control in health care, it is pertinent to analyze the outcomes and performance metrics of our operations regularly, thus aiding in the development of an established evidence base to advocate for our respective patients. [ABSTRACT FROM AUTHOR]

To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair. Retrospective, population-based cohort study. Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023. A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race. Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort. Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13–4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13–2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64–3.16). A dermatologic history of KHF may be a risk factor for PVR after RD repair. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

This document provides a list of articles published in the International Journal of Molecular Sciences, covering various topics in dermatology. The field of dermatology has made significant advancements through the integration of basic research and clinical dermatology, leading to the development of targeted therapies and personalized treatment approaches. Genetic research, immune mechanisms, biologic drugs, and laser technologies have all contributed to the management of skin diseases. However, challenges remain, and interdisciplinary collaboration, along with the integration of artificial intelligence and machine learning, is necessary for further progress. The articles in this list focus on conditions such as vitiligo, psoriasis, neutrophilic dermatosis, non-melanoma skin cancer, and skin drug reactions, providing valuable insights into their pathogenesis, treatment strategies, and genetic influences. The authors have declared no conflicts of interest. [Extracted from the article]

This article provides information on myopathic Ehlers-Danlos syndrome (mEDS), a rare genetic disorder. It discusses the similarities and differences between mEDS and Ullrich congenital muscular dystrophy (UCMD). The study suggests that genetic analysis, muscle imaging, and muscle pathology can help distinguish between the two conditions. The article presents a case report of a 23-month-old girl with severe phenotypes of mEDS. It also includes a table with alphanumeric data about individuals with different conditions, but the purpose of the table is unclear without further information. Additionally, the article discusses muscle MRI data comparing a patient with mEDS to a patient with UCMD, highlighting differences in muscle involvement. The study also examines muscle biopsies and identifies a novel genetic variant associated with the most severe phenotype of mEDS. Overall, the article emphasizes the importance of various diagnostic tools in differentiating mEDS from UCMD/BM. [Extracted from the article]

Skin pathological fibrosis conditions, such as hypertrophic scars (HS) and keloids, where the scar tissue is raised and extends beyond the original wound boundary, are aesthetically unappealing and sometimes painful or itchy, significantly impacting the life quality of patients. In this review, the advances of nanobiomaterials in treating skin pathological fibrosis are summarized and discussed. The focus is on the therapeutic approaches to cellular and molecular targets of HS, highlighting the potential of nanotechnology in scar management. The biofunctional nanomaterials can modulate inflammation, regulate angiogenesis, and promote fibroblast apoptosis. The nanotechnology‐based drug delivery systems such as liposomes, ethosomes, and dendritic macromolecules can improve the solubility, stability, and efficacy of drugs, and enhance precise delivery, resulting in better outcomes in HS therapy. Integrating nanomaterials or nanostructures into hydrogels, nanofibers, and microneedles can enhance the biological functionality and maximize the therapeutic effect of nanoparticles (NPs) at the wound site. The important potential of nanotechnology‐based scar treatment should be further explored to overcome the current challenges and promote its application in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aims to compare the efficacy rates in treating hypertrophic scars among four distinct groups of patients who either underwent fractional Erbium: yttrium‐aluminum‐garnet (Er:YAG) laser or microplasma radiofrequency technology as standalone treatments or in combination with compound betamethasone transdermal administration. Method: The study retrospectively examined 208 patients treated at our institution from April 2011 to December 2022 for hypertrophic scars, receiving no less than three treatments (with an interval of 8 weeks between each). The patients were categorized into four groups: the F group (treated with fractional Er:YAG laser), the F + B group (treated with fractional Er:YAG laser combined with compound betamethasone transdermal administration), the P group (treated with microplasma radiofrequency technology), and the P + B group (treated with microplasma radiofrequency technology combined with compound betamethasone transdermal administration). The therapeutic effects were evaluated based on the changes in the Vancouver Scar Scale (VSS) scores before and after treatment in these groups. Results: There was no statistically significant difference in the VSS scores among the four groups before treatment. After undergoing three sessions of the aforementioned four types of treatment, all groups showed a decrease in VSS scores, with average posttreatment VSS scores for the F group scored 5.15 ± 2.084, F + B group scored 3.7 ± 1.781, P group scored 4.41 ± 1.933, and P + B group scored 3.16 ± 1.775, respectively. With an increasing number of treatments, the total effective rate gradually increased in all four groups, and the combination treatment using compound betamethasone transdermal administration proved more effective than the standalone treatment. Conclusion: All four treatments yielded favorable outcomes, with the combined therapy involving compound betamethasone transdermal administration proving more effective than the standalone treatments, meriting further clinical attention. [ABSTRACT FROM AUTHOR]

The role of glial scars in the pathophysiology of spinal cord injury (SCI) is widely recognized, as they pose physical barriers against axonal regeneration and persistent chronic inflammation by releasing cytotoxic agents, thereby impeding nerve repair. Consequently, preventing glial scarring has emerged as an important therapeutic objective in SCI management. Following SCI, astrocytes undergo a phenotypic transition into scar‐forming astrocytes, which critically depends on the activation of inflammatory responses and the integrin‐N‐cadherin pathway. To explore improved SCI treatment, a nano‐antagonist hydrogel (Nano‐ant Gel), comprising N‐cadherin nano‐antagonists and a polyphenol hydrogel designed to inhibit glial scarring by mitigating inflammatory response and modulating astrocyte behavior, thereby facilitating spinal cord‐injury repair, is developed and characterized. The hydrogel exhibits notable anti‐inflammatory properties, specific calcium ion‐adsorption capabilities, and antagonistic effects against N‐cadherin, effectively impeding the formation and aggregation of scar‐forming astrocytes. Its efficacy is comprehensively assessed using a model of contusive SCI, with which it effectively inhibits glial scar formation and promotes axonal regeneration. Notably, the Nano‐ant Gel significantly improves the locomotor functions of mice with SCI, suggesting that it represents a promising approach for treating the condition. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI. The heterogeneous characters of fibrotic scars after spinal cord injury remains unclear. Here, the authors show the heterogeneous distribution, source and function of meningeal fibroblasts and perivascular fibroblasts in fibrotic scars. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) with noninvasiveness and high safety has emerged as a promising therapeutic approach for the management of hypertrophic scars (HS). However, the low transdermal delivery and overexpressed levels of intracellular glutathione (GSH) severely hinder its therapeutic effectiveness. Herein, a multifunctional biomimetic nanoplatform (NDs@EV‐RGD) composed of arginine‐glycine‐aspartic acid (RGD)‐modified cucumber‐derived extracellular vesicles (EVs) and copper‐based metal‐organic framework nanodots (Cu‐MOF NDs) is designed for PDT‐mediated HS treatment. The EVs with low Young's modulus exhibit excellent deformability which endow NDs@EV‐RGD with the capacity to overcome the compact stratum corneum barrier, thereby significantly improving their transdermal delivery efficiency. Notably, the RGD targeting peptide displays specific binding to α1β1 integrin on the fibroblast membranes within HS, leading to the high accumulation efficiency of NDs@EV‐RGD at the HS site. Under near‐infrared laser irradiation, NDs@EV‐RGD efficiently generates abundant reactive oxygen species, inducing the apoptosis of excessively proliferated fibroblasts. Moreover, Cu‐MOF NDs interact with the local GSH, leading to GSH depletion and a significant enhancement in PDT efficacy. Furthermore, NDs@EV‐RGD demonstrates a remarkable therapeutic effect in improving the appearance of HS in a rabbit ear HS model, promoting the apoptosis and remodeling of collagen fibers. Therefore, this work provides a promising biomimetic platform for HS treatment. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine‐enhanced computed tomography (LIE‐CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT‐derived scar substrates in NICM. We sought assess the relationship between scar location on LIE‐CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT.From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial‐enhanced imaging for anatomical modeling and LIE‐CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure.Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow‐up of 120 days (interquartile range [IQR]: 41–365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8–65). CT‐derived total scar volume positively correlated with intrinsic QRS duration (r = .34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0–8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3–2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9–10.7]; p = 0.078; lateral scar OR: 1.7 [0.5–5.9]; p = 0.391).In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE‐CT have nearly threefold increased risk of need for repeat ablation. [ABSTRACT FROM AUTHOR]

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 μg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco's phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In Hurler syndrome, corneal opacification is a common finding but rarely manifests as hypertrophic scars. A 6‐year‐old boy with Hurler syndrome had a hypertrophic scar on his left eye, which was successfully treated with superficial keratectomy. [ABSTRACT FROM AUTHOR]

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well‐defined molecular mechanism governing hypertrophic scarring has led to less‐than‐ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF‐β/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL‐1 and COL‐3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF‐β1/Smad3 pathway by suppressing TGF‐β1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen‐based extracellular matrix and fibrosis through the TGF‐β1/Smad3 pathway. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM‐derived EVs represent a promising cell‐free therapy for the treatment of cardiac fibrosis. To this end, we optimized the culture conditions of human adult CMs to obtain a large yield of EVs without compromising cellular integrity by using a defined combination of small molecules. EVs were isolated by ultracentrifugation, and their characteristics were analysed. Finally, their effect on fibrosis was tested. Treatment of TGFβ‐activated human cardiac fibroblasts with EVs derived from CMs using our culture system resulted in a decrease in fibroblast activation markers and ECM accumulation. The rescued phenotype was associated with specific EV cargo, including multiple myocyte‐specific and antifibrotic microRNAs, although their effect individually was not as effective as the EV treatment. Notably, pathway analysis showed that EV treatment reverted the transcription of activated fibroblasts and decreased several signalling pathways, including MAPK, mTOR, JAK/STAT, TGFβ, and PI3K/Akt, all of which are involved in fibrosis development. Intracardiac injection of CM‐derived EVs in an animal model of cardiac fibrosis reduced fibrotic area and increased angiogenesis, which correlated with improved cardiac function. These findings suggest that EVs derived from human adult CMs may offer a targeted and effective treatment for cardiac fibrosis, owing to their antifibrotic properties and the specificity of cargo. [ABSTRACT FROM AUTHOR]

[Display omitted] • Attenuated auxotrophic Salmonella Typhimurium was utilized for the anti-tumor effect. • Reduction of endotoxicity was rendered by lipid A modification. • Regulated expression of ClyA at higher cell density under QS signaling. • Engineered Salmonella Typhimurium enhanced safety and tumor invasion. • ClyA expressing Salmonella reduced 67 % of tumors in mouse CT 26 cancer model. The limitations of conventional cancer therapies necessitate target-oriented, highly invasive, and safe treatment approaches. Hence, the intrinsic anti-tumor activity of Salmonella can offer better options to combat cancers. This study aims to utilize attenuated Salmonella and deliver cytolytic protein cytolysin A (ClyA) under quorum sensing (QS) signaling for precise localized expression in tumors but not in healthy organs. The therapeutic delivery strain was imposed with tryptophan auxotroph for selective colonization in tumors by trpA and trpE deletion, and lipid-A and O-antigen were altered by pagL and rfaL deletions using lambda red recombination method. The strain was transformed with the designed QS-controlled ClyA expression vector which was validated by western blot. The in vivo passaged therapeutic strain was used for treatment four times at a weekly interval, with a dose of 5 × 106 CFU/mouse for cancer therapy. The attenuated strain induced minimal endotoxicity-related cytokines TNF-α, IL-1β, and IFN-γ and exhibited adequate colonization despite earlier exposure in mice. The QS-controlled ClyA expression was confirmed by western blot from bacterial cultures grown at different cell densities. The results demonstrated that the in vivo passaged strain preferentially colonized the tumor after vacating the spleen, liver, and lung, leaving no outward histological scars. The anti-cancer effect of the designed construct was evaluated in the murine CT26 colon cancer model. The expression of ClyA increased tumoricidal activity by 67 % compared to vector control. Hence, the anti-tumor effect of the engineered Salmonella strain was improved by ClyA expression via QS activation after achieving the threshold bacterial cell density. Further, immunohistochemical staining of the tumor and other organs corroborated the QS-controlled tumor-specific expression of ClyA. Overall, the results imply that the developed anti-cancer Salmonella has low endotoxicity and QS-controlled expression of ClyA as beneficial safety elements and supports recurrent Salmonella inoculation by O-antigen deficiency. [ABSTRACT FROM AUTHOR]

Hypertrophic scarring is a significant complication post burn injury, especially for delayed healing after 3 weeks. Burn injuries healing prior to 3 weeks also have the potential to develop hypertrophic scarring, even when prescribed prophylactic conservative scar interventions. A retrospective chart audit reviewed 326 burn patients treated at a paediatric tertiary hospital from 2014 to 2019 who sustained a partial thickness burn, healed >14 days and did not receive skin grafting. A scar was deemed hypertrophic if >1 mm in height. Early hypertrophic scar prevalence was defined as 3–6 months post burn, while persistent hypertrophic scarring was defined as 12–18 months post burn. Median days to wound closure was 18. The prevalence of early and persistent hypertrophic scarring was 56.1% and 16.3%, respectively. Seventeen (5.2%) children underwent medical interventions for scar modulation. Early signs of hypertrophic scarring were seen in just over half the patients presenting to burn therapy and despite scar intervention, persistent hypertrophic scarring was seen in 16.3%. At both time points, just over half of the children presenting healed between 14 and 21 days. Therefore, children healing prior to 21 days have potential to develop hypertrophic scarring. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scars (HS) are dermal diseases characterized by excessive fibroblast proliferation and collagen deposition following burns or trauma. While Tenascin-C (TNC)'s role in promoting visceral fibrosis has been established, its impact on skin tissue fibrosis remains unclear. This study aims to investigate the effects of TNC on HS. Methods: RNA sequence and IHC techniques were used to examine the upregulation of TNC gene in human hypertrophic scar tissue compared to normal tissues. Knockdown of TNC in Human skin fibroblasts (HFF-1) cells was achieved, and expression of Col1 and Col3 was evaluated using qPCR. Sirius red collagen staining assessed impact on total collagen content and ECM deposition. Effects on cell proliferation and migration were investigated through cck-8 and cell scratch experiments. Lentivirus infection was used to knock out TNC, and resulting samples were injected into ear wound of rabbits. Effects of TNC knockout on ear scar formation were measured using digital morphology, ultrasound, SEI, H&E, and Masson trichrome methods. Results: Cell experiments: downregulation of TNC decreased Col1 and Col3 expression, leading to reduced collagen production and extracellular matrix deposition. It did not affect HFF-1 cell proliferation and migration. Animal experiments: TNC knockdown promoted wound healing and reduced collagen deposition in rabbit ears. Conclusion: This study suggests that knocking down TNC inhibits collagen formation and extracellular matrix deposition, thereby inhibiting hypertrophic scar formation. Therefore, TNC can be considered a potential biomarker for HS formation and may offer promising treatment strategies for clinical management of hypertrophic scars. [ABSTRACT FROM AUTHOR]

Partial-thickness burns are the most common form of burns, affecting the dermis and possibly resulting in scarring and infection. The Spincare System is a new device that uses electrospinning technology to create a temporary skin-like matrix that can be applied to wounds. This study evaluated the performance, safety, and efficacy of Spincare in treating superficial to partial-thickness burns not considered for surgery. A prospective single-arm, open-label, multicenter study was conducted in 3 adult burn units across Israel. Forty-four patients with superficial to intermediate burns of up to 10% of TBSA were enrolled. Spincare was applied to the wounds, and follow-up visits were performed on days 7, 14, and 21 and months 3 and 6 posttreatment. Thirty-one patients with 36 wounds completed the day 21 visit. The mean wound healing area on day 21 was 97.26 ± 9.41%, and the mean healing time was 12.8 ± 4.3 days. Only one moderate adverse event was observed concerning the treatment, and it is important to acknowledge the potential progression of this hypertrophic scar into a keloid. This study demonstrated that Spincare is a safe and effective device for treating superficial to intermediate partial-thickness burns. Spincare achieved rapid and complete wound healing with a low incidence of adverse events. [ABSTRACT FROM AUTHOR]

Burn injuries are frequently disastrous catastrophes that can cause significant skin damage and frequently result in hypertrophic scarring. Recovery from burn injury includes 3 domains—medical, functional, and psychiatric. Psychological concerns affect both the quality of life and the disease recovery. This study assesses the prevalence of major depression or clinically significant symptoms of depression among patients hospitalized for acute burn injury, as well as their persistence once diagnosed. It is a prospective cohort that was studied in 1%-40% of patients with body surface area burn, where the Beck Depression Inventory was used as a depressive symptom measure. A total of 108 patients were included in the study, out of which 42 (38.8%) exhibited depressive symptoms. Type of burn did not affect the prevalence of depression, whereas total body surface area had an impact on prevalence rate. The Beck Depression Inventory score assessment during the study revealed that 8.4% of participants exhibited worsening of scores during the study period and only 3.4% showed improvement throughout the study. Patients with mild depressive symptoms at admission were likely to recover, whereas those with severe depressive symptoms were less likely to recover from the psychological state. To conclude, depression was more prevalent among burn survivors from the Indian community. [ABSTRACT FROM AUTHOR]

Introduction and purpose In recent years, there has been notable progress in the role of light-emitting technologies, including lasers and other energy-based devices, across various medical disciplines. Dermatology stands out as one of the prominent fields where laser treatments have gained significant popularity. In the clinical setting, a variety of laser types are utilized. A fundamental aspect of ensuring the safe use of laser devices involves comprehending their mechanisms at the tissue level. This knowledge enables practitioners to attain the desired outcomes effectively while minimizing the risk of complications. Lasers have demonstrated effectiveness in treating cutaneous vascular conditions because of their capacity to selectively target intravascular oxyhemoglobin. Rosacea, juvenile hemangioma, and port wine stains are among the vascular skin conditions for which laser therapy has shown notable success. Laser therapy is employed in treating hypertrophic scars, keloids, and acne scars because it facilitates the restructuring of the skin's architecture at the scar site, with the goal of minimizing its size and visibility. Laser therapy stands as the gold standard for removing tattoos. Materials and methods The methodology for conducting literature search involved utilizing medical subject headings terms to explore PubMed. Search terms included: “lasers”, “intense pulsed light”, “dermatology”, “rosacea”, “acne”, “scars”, “tattoo removal”. Conclusions Laser dermatological treatments are gaining popularity worldwide, driving new innovations and clinical applications. This review highlights the significant role and diverse clinical applications of lasers and intense pulsed light in dermatological practice. Improving the quality of skin in patients suffering from skin diseases can significantly increase their quality of life. [ABSTRACT FROM AUTHOR]

Diabetic wounds, a prevalent diabetes complication, pose significant challenges in treatment. MicroRNA-engineered exosomes (miR-exo) are a promising new treatment for diabetic wounds; however, their mechanism remains to be completely understood. Therefore, we aimed to conduct a meta-analysis to evaluate the efficacy of miR-exo treatment in the management of diabetic wounds. To achieve this aim, academic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were searched for papers published before July 4, 2023. Outcome indicators (e.g., rate of wound healing, neovascular count, rate of re-epithelialization, deposition of collagen, breadth of scar, and inflammatory factors) were assessed. Six studies (total of 72 animals) met inclusion criteria and were analyzed. The amalgamated data revealed that miR-exo treatment exhibited superior results compared to those of control therapy. miR-exo treatment significantly enhanced the rate of wound healing, increased the number of neovascular formations, accelerated the rate of re-epithelialization, increased collagen deposition, reduced scar width, while significantly downregulating the expression of inflammatory factors. Our findings indicate that miR-exo treatment augments overall diabetic wound healing, especially when administered in conjunction with innovative dressings. To ascertain the optimal parameters for miR-exo treatment in managing diabetic wounds, future studies must encompass rigorous, large-scale, double-blinded clinical trials while incorporating long-term follow-up assessments for enhanced reliability and accuracy. [ABSTRACT FROM AUTHOR]

Abstract Scar tissue is the inevitable result of repairing human skin after it has been subjected to external destructive stimuli. It leads to localized damage to the appearance of the skin, accompanied by symptoms such as itching and pain, which reduces the quality of life of the patient and causes serious medical burdens. With the continuous development of economy and society, there is an increasing demand for beauty. People are looking forward to a safer and more effective method to eliminate pathological scarring. In recent years, adipose-derived stem cells (ADSCs) have received increasing attention from researchers. It can effectively improve pathological scarring by mediating inflammation, regulating fibroblast proliferation and activation, and vascular reconstruction. This review focuses on the pathophysiological mechanisms of hypertrophic scarring, summarizing the therapeutic effects of in vitro, in vivo, and clinical studies on the therapeutic effects of ADSCs in the field of hypertrophic scarring prevention and treatment, the latest application techniques, such as cell-free therapies utilizing ADSCs, and discussing the advantages and limitations of ADSCs. Through this review, we hope to further understand the characterization of ADSC and clarify the effectiveness of its application in hypertrophic scarring treatment, so as to provide clinical guidance.

Yul Hee Kim,1 Han-Seul Kim,1 Hyeung Kyoo Kim,2 Soo Young Kim,2 Jeonghun Lee,2 You Chan Kim,1 Young Joon Park1 1Department of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea; 2Department of Surgery, Ajou University School of Medicine, Suwon, Republic of KoreaCorrespondence: Young Joon Park, Department of Dermatology, Ajou University Hospital, 164, World Cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-Do, Suwon, Republic of Korea, Tel +82-31-219-5187, Email aro@ajou.ac.krPurpose: Early intervention of surgical scars with a pulsed dye laser is known to effectively prevent pathologic scars. Despite multiple reports on the effectiveness of the treatment, very few studies have demonstrated its appropriate initiation timing. In this study, our objective was to determine the optimal timing for initiating laser treatment following thyroidectomy.Methods: This study retrospectively analyzed 91 patients undergoing pulsed dye laser treatment post-thyroidectomy, grouping them by treatment initiation timing. The patients underwent treatment at intervals of 3– 4 weeks with at least five sessions. Those with a high pliability score were injected with intralesional corticosteroids. The Antera 3D® skin imaging analyzer was used to assess biophysical parameters.Results: The total Vancouver Scar Scale score significantly reduced after treatment in all groups. The Vancouver Scar Scale score reduction rate was significantly higher after treatment in the group for which the treatment was initiated within 3 weeks of surgery. The pigmentation and erythema score analyzed by Antera 3D® was also lower in this group.Conclusion: Early intervention using a pulsed dye laser within 3 weeks of thyroidectomy can substantially inhibit pathological scar development, providing physicians with a guide for optimal treatment commencement.Keywords: hypertrophic scars, laser treatment of scar, scar, pulsed dye laser

Wound management is an important issue that places enormous pressure on the physical and mental health of patients, especially in cases of infection, where the increased inflammatory response could lead to severe hypertrophic scars (HSs). In this study, a hydrogel dressing was developed by combining the high strength and toughness, swelling resistance, antibacterial and antioxidant capabilities. The hydrogel matrix was composed of a double network of polyvinyl alcohol (PVA) and agarose with excellent mechanical properties. Hyperbranched polylysine (HBPL), a highly effective antibacterial cationic polymer, and tannic acid (TA), a strong antioxidant molecule, were added to the hydrogel as functional components. Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA. In the in vivo studies of methicillin-resistant Staphylococcus aureus (MRSA) infection, the hydrogel had shown obvious promotion of wound healing, and more profoundly, significant suppression of scar formation. Due to the common raw materials and simple preparation methods, this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.

Excessive scar formation such as hypertrophic scars and keloids, resulting from trauma or surgical procedures, present a widespread concern for causing disfigurement, discomfort, and functional limitations. Macrophages play pivotal roles in maintaining tissue homeostasis, orchestrating tissue development, repair, and immune responses, and its transition of function and phenotype plays a critical role in regulating the balance between inflammation and tissue regeneration, which is central to cutaneous scar formation. Recent evidence suggests the involvement of Sonic Hedgehog (SHH) in the induction of anti-inflammatory M2-like macrophage phenotypes within tumor microenvironments. In our study, we observed increased SHH expression in human hypertrophic scars, prompting an investigation into its influence on macrophage polarization, efferocytosis, and cutaneous scar formation. Our findings reveal that SHH can enhance oxidative phosphorylation (OXPHOS) in macrophages, augment macrophage efferocytosis, and promote M2 polarization, finally contributing to the progression of cutaneous scar formation. Notably, targeting SHH signaling with vismodegib exhibited promising potential in mitigating scar formation by reversing the effects of enhanced OXPHOS and M2 polarization in macrophages. In conclusion, this study underscores the critical roles of macrophage metabolism, particularly OXPHOS, efferocytosis and SHH signaling in cutaneous scar formation. Understanding these mechanisms provides new avenues for potential interventions and scar prevention strategies. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) is a complex health problem that affects millions of individuals worldwide. It consists of two main types, Ulcerative Colitis (UC) and Crohn's Disease (CD), which have distinct characteristics and symptoms. Both UC and CD can lead to intestinal fibrosis, a condition characterized by excessive tissue scarring. Current therapies for IBD aim to induce remission, improve quality of life, and prevent complications, but there is still a need for more effective treatments. Recent research has also highlighted the role of the gut microbiota in IBD and the potential for targeting it to modulate inflammation and fibrosis. Overall, understanding the molecular mechanisms underlying IBD is crucial for developing targeted therapies and improving long-term outcomes for patients. [Extracted from the article]

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar—a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. Methods: The transforming growth factor-β1 (TGF-β1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. Results: Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-β1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. Conclusions: Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism. [ABSTRACT FROM AUTHOR]

Background: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-β (TGF-β), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-β remain poorly understood. Methods: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-β-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. Results: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-β-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-β-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-β treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. Conclusion: Our results shed light on KAT14 as a key effector of TGF-β–induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis. [ABSTRACT FROM AUTHOR]