Prevention Of Scars Research Articles

Prophylaxis Options in Children With a History of Recurrent Urinary Tract Infections: A Systematic Review.

The prevention of urinary tract infection recurrence (UTI) in children has been a challenge yet to be solved. Current practice in children with recurrent UTI (RUTI) suggests that antibiotic prophylaxis may prevent further episodes of UTI and future complications. To conduct a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis options for the prevention of UTI and kidney scarring in children with a history of RUTI. We conducted a systematic literature search through major electronic databases (PubMed/Medline, Scopus and Cochrane Library) up to November 26th, 2023. Mean difference and SD were used for continuous outcomes and odds ratio for dichotomous outcomes. Our meta-analysis included 3335 participants from 23 studies. The primary outcome was the effect of the different prophylaxis options on the incidence of symptomatic UTI in children with RUTI during prophylactic treatment. Cranberry products and nitrofurantoin lead to lower odds of symptomatic UTI episodes during prophylaxis compared with the control group and control, trimethoprim-sulfamethoxazole, or trimethoprim groups accordingly. Nitrofurantoin may be the best option for UTI incidence reduction compared with all available documented interventions. No prophylaxis option has been shown to reduce kidney scarring. Nitrofurantoin and cranberry products may decrease the incidence of symptomatic UTI episodes in pediatric patients with a history of RUTI. Future randomized control trials studying nonantibiotic prophylaxis options focusing on children with UTI recurrence and the risk for kidney scarring are needed to draw further conclusions.

Roles of extracellular vesicles from mesenchymal stem cells in regeneration.

Mesenchymal stem cells (MSCs) are highly valued in regenerative medicine due to their ability to self-renew and differentiate into various cell types. Their therapeutic benefits are primarily due to their paracrine effects, in particular through extracellular vesicles (EVs), which are related to intercellular communication. Recent advances in EV production and extraction technologies highlight the potential of MSC-derived EVs (MSC-EVs) in tissue engineering and regenerative medicine. MSC-EVs offer several advantages over traditional cell therapies, including reduced toxicity and immunogenicity compared to whole MSCs. EVs carrying functional molecules such as growth factors, cytokines and miRNAs play beneficial roles in tissue repair, fibrosis treatment and scar prevention by promoting angiogenesis, skin cell migration, proliferation, extracellular matrix remodeling and reducing inflammation. Despite the potential of MSC-EVs, there are several limitations to their use, including variability in quality, the need for standardized methods, low yield, and concerns about the composition of EVs and the potential risks. Overall, MSC-EVs are a promising alternative to cell-based therapies, and ongoing studies aim to understand their actions and optimize their use for better clinical outcomes in wound healing and skin regeneration.

Investigating the impact of botulinum toxin type a on the migration of normal human dermal fibroblasts: An invitro wound healing assay.

Botulinum toxin A (BoNT-A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT-A. However, the data regarding the effect of BoNT-A on the migration of normal human dermal fibroblasts (NHDF) is limited. The aim of this study was to investigate the inhibitory effect of different types and dilutions of BoNT-A on the migration of NHDF. In vitro scratch wound assay, NHDF cells were cultured, incubated, and subjected to scratching using a sterile tip. Subsequently, the scratched NHDF monolayer was treated with different types of BoNT-A, including onabotulinumtoxinA (ONA), incobotulinumtoxinA (INCO), prabotulinumtoxinA (PRABO), or letibotulinumtoxinA (LETI), at varying concentrations of 10, 20, 25, 40, 50, and 100 units/milliliter (U/mL). Additionally, abobotulinumtoxinA (ABO) was administered at concentrations of 33, 50, 66, 71, 100, 150, 300, and 500 U/mL. Normal saline solution (NSS) served as a negative control. The extent of NHDF migration was evaluated by comparing each dilution of BoNT-A with the controls using high-content imaging at the 48-h time point. Furthermore, the viability of the of NHDF was assessed. The concentrations of 25, 40, and 50 U/mL of ONA (p < 0.001) and 25 U/mL of LETI (p < 0.05) demonstrated significantly inhibited NHDF migration in comparison to the control group. Conversely, all dilutions of PRABO, INCO, and ABO exhibited comparable NHDF migration to that of the control group. Regarding NHDF viability, no significant decrease was observed across any of the BoNT-A types and dilutions. Different types and dilutions of BoNT-A demonstrated variable inhibitory effects on NHDF migration invitro. The selection of BoNT-A formulation may significantly impact the clinical outcome of scar prevention related to fibroblast migration.

A Systematic Review on Biochemical Perspectives on Natural Products in Wound Healing: Exploring Phytochemicals in Tissue Repair and Scar Prevention.

Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, including chlorogenic acid, thymol, and eugenol from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages. This review provides mechanistic insights into the significant role of pharmacologically demonstrated natural products in wound healing processes.

Enhanced Targeted Drug Delivery for Scar Prevention: Clathrin‐Coated Solid Lipid Nanoparticles for Model Drug Encapsulation

AbstractExcessive scar formation is a major complication of wound healing. Premature release of anti‐scarring drugs can negatively impact healing. This study aims to develop a targeted delivery system for the controlled release of anti‐scarring drugs during the scar formation stage. Solid lipid nanoparticles (SLNs) coated with Clathrin, a cage‐like protein, to prevent premature drug release is developed. Insulin‐like growth factor (IGF) is conjugated to the SLNs for targeted delivery via its affinity for connective tissue growth factor (CTGF), a protein overexpressed during scar formation. The IGF‐Clathrin‐SLNs exhibited a size of 300 ± 20 nm and a zeta potential of 9.23 ± 0.4 mV. In vitro studies demonstrated sustained release of the encapsulated drug‐ kynurenic acid; less than 10% of kynurenic acid is released within three days, while over 50% is released within 10 h upon Clathrin removal using a surfactant at pH 8. Cellular uptake studies confirmed targeting efficacy. Fibroblasts with low CTGF expression displayed low uptake (&lt;10%), whereas MCF7 cells with high CTGF expression showed significantly higher uptake (80%). This work demonstrates a promising targeted delivery platform for the controlled release of anti‐scarring drugs during scar formation.

Effects of low dose skin tissue derived peptides on the function and collagen expression of keloid fibroblasts

This study aims to investigate the effects of the skin tissue derived peptides on proliferation, apoptosis, migration and collagen expressions in keloid fibroblasts. From January 2015 to January 2017, patients with hypertrophic scar who underwent surgical excision in department of plastic surgery of Nanjing maternal and child health hospital were included in this retrospective study. Four peptides were selected from the differential peptides between human hypertrophic scar and normal skin tissue. They were named as peptide deregulated in hypertrophic scar 2-5 (PDHPS2-5). Bioinformatics and functional analysis were performed. A low dose of 10 μmol/L of four peptides were respectively added to the culture medium of human primary keloid fibroblasts for 24 h. Cell counting kit-8 (CCK-8) were used to detect the changes in cell viability. Cell apoptosis was detected by flow cytometry. Cell migration ability was checked by Transwell chamber. The protein expressions of collagen COL1A2 (Collagen type I alpha 2) and the myofibroblast marker gene ACTA2 (Actin alpha 2) were analyzed by Western blot. The results showed that bioinformatics prediction analysis revealed that peptide PDHPS4 has the longest half-life and the highest thermal stability. Compared with the control group, low dose of four peptides had no significant effect on the survival rate and apoptosis of keloid fibroblasts tested by CCK-8 assay and flowcytometry. Transwell analysis showed that one peptides (PDHPS5) can significantly inhibit the cell migration ability (The optical density value in Control is 0.81±0.11, in PDHPS5 is 0.27±0.03, t=8.61, P=0.001). Western blot analysis showed that four peptides (PDHPS2, PDHPS3, PDHPS4, PDHPS5) can significantly inhibit the protein expressions of COL1A2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.21±0.04, in PDHPS3 is 0.26±0.03, in PDHPS4 is 0.53±0.04, in PDHPS5 is 0.73±0.04, t=31.38, 38.54, 18.88, 11.07 respectively, all P value are less than 0.01). Three peptides (PDHPS2, PDHPS3, PDHPS5) can significantly inhibit the protein expressions of ACTA2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.64±0.05, in PDHPS3 is 0.77±0.06, in PDHPS5 is 0.47±0.07, t=12.08, 6.38, 14.06 respectively, all P value are less than 0.01). In conclusion, the differentially expressed peptides in human hypertrophic scar tissue can affect the function of keloid fibroblasts and collagen expressions to varying degrees. Among them, two peptides (PDHPS2,PDHPS3) significantly inhibit the protein expressions of COL1A2 and ACTA2. The peptide PDHPS5 has high stability, significantly suppresses cell migration, and reduces the protein expressions of COL1A2 and ACTA2, which may provide a new strategy for scar prevention and treatment.

Dose-Dependent Effects of Botulinum Toxin Type A on Prevention of Postoperative Scars in Various Regions in the Body: A Prospective, Double-Blind Randomized Controlled Trial.

Botulinum toxin type A (BTXA) can improve wound healing and reduce scar formation; however, the exact dose required to prevent postoperative scarring across various anatomical sites remains unclear. This study aimed to investigate the effectiveness and optimal concentrations of BTXA for preventing postoperative scarring across various common surgical sites throughout the body. In this prospective randomized controlled trial, 46 patients with benign skin tumors received injections of 1, 2.5, or 5U/0.1mL of BTXA or 0.9% saline immediately following surgical tumor excision on both sides of the incisions. Follow-ups were conducted at 7days, 15days, and 1, 3, and 6months postoperatively. Patient-reported adverse events and standardized digital photographs were collected. Scar formation was assessed using the modified Stony Brook Scar Evaluation Scale (mSBSES). All 46 patients completed the trial without severe complications. The mSBSES scores were higher in the experimental groups at all follow-ups. The 5U/0.1mL BTXA dose group demonstrated optimal scar prevention at all high-risk sites for scar hyperplasia. No significant difference was observed between the 2.5U/0.1mL and 5U/0.1mL doses for intermediate-risk sites, while 1U/0.1mL dose was sufficient for low-risk sites. Overall, 86.5% of patients were satisfied with their treatments, with 16.3% being very satisfied. Early postoperative BTXA injection can reduce or prevent hypertrophic scarring, with optimal doses ranging from 1 to 5U/0.1mL depending on the surgical site, supporting broader clinical application of BTXA. The effectiveness of different concentrations of botulinum toxin type A (BTXA) in preventing postoperative scarring was compared, expanding the scope of previous research, which focused only on the head, face, and neck regions, to include the trunk and extremity areas. Different optimal injection strategies were determined based on different surgical sites and their risks of developing hypertrophic scars. The study demonstrates that BTXA not only reduces scar formation but also enhances patient satisfaction and reduces postoperative itching and pain, contributing to overall better postoperative outcomes. By establishing the efficacy and optimal dosing of BTXA for various surgical sites, this research supports the potential for broader clinical application of BTXA in aesthetic and reconstructive surgeries. 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 .

The effect of inflammatory cytokines on the risk of hypertrophic scar: a mendelian randomization study.

Hypertrophic scar (HS) results from burns or trauma, causing aesthetic and functional issues. However, observational studies have linked inflammatory cytokines to HS, but the causal pathways involved are unclear. We aimed to determine how circulating inflammatory cytokines contribute to HS formation. Two-sample Mendelian randomization (MR) was used to identify genetic variants associated with hypertrophic scar in a comprehensive, publicly available genome-wide association study (GWAS) involving 766 patients and 207,482 controls of European descent. Additionally, data on 91 plasma proteins were drawn from a GWAS summary involving 14,824 healthy participants. Causal relationships between exposures and outcomes were investigated primarily using the inverse variance weighted (IVW) method. Furthermore, a suite of sensitivity analyses, including MR‒Egger and weighted median approaches, were concurrently employed to fortify the robustness of the conclusive findings. Finally, reverse MR analysis was conducted to evaluate the plausibility of reverse causation between hypertrophic scar and the cytokines identified in our study. In inflammatory cytokines, there was evidence of inverse associations of osteoprotegerin(OPG) levels(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01), and leukemia inhibitory factor(LIF) levels(OR = 0.51, 95% CI = 0.32 ∼ 0.82, p = 0.01) are a nominally negative association with hypertrophic scar risk, while CUB domain-domain-containing protein 1(CDCP1) level(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01) glial cell line-derived neurotrophic factor(GDNF) levels(OR = 1.42, 95% CI = 1.03 ∼ 1.96, p = 0.01) and programmed cell death 1 ligand 1(PD-L1) levels(OR = 1.47, 95% CI = 1.92 ∼ 2.11, p = 0.04) showed a positive association with hypertrophic scar risk. These associations were similar in the sensitivity analyses. According to our MR findings, OPG and LIF have a protective effect on hypertrophic scar, while CDCP1, GDNF, and PD-L1 have a risk-increasing effect on Hypertrophic scar. Our study adds to the current knowledge on the role of specific inflammatory biomarker pathways in hypertrophic scar. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for hypertrophic scar prevention and treatment.

Multi-functional scar tissue discrimination platform construction and exploration of molecular mechanism for scar formation

Scars that form after skin injury can cause structural and functional skin damage. Currently, scar tissue determination relies mainly on doctors’ subjective observations and judgments and lacks objectivity. However, current deep learning models can only achieve specific discrimination using unimodal data, which limits the comprehensive understanding of scar tissue and may reduce accuracy and stability. To solve these problems, in this study, a skin scar recognition platform based on advanced deep learning and a weighted aggregation network fusion method is proposed. It is implemented using a residual network-based CNN model and a logistic regression model with L1 regularization and is suitable for both unimodal and multimodal data. The experimental results showed that the proposed platform achieved a satisfactory accuracy of 98.26% for image discrimination. In the gene discrimination model test performed on a test dataset containing 17 gene expression samples, all samples were accurately discriminated. In addition, the proposed multimodal discrimination model achieved a discrimination accuracy of 98.23%. These results validate the effectiveness of deep feature extraction and multimodal feature fusion techniques for image discrimination tasks. On this basis, to deeply explore the pathogenesis of scar formation, a method with the ability to integrate regularization, sparsity, and orthogonality constraints, multiconstraint joint non-negative matrix factorization (MCJNMF), was used to explore the genetic correlation between collagen micrographic image features and gene expression data. In this study, we confirmed the association between the calcium signaling pathway, MAPK signaling pathway, and collagen fiber repair, and successfully identified 11 potential therapeutic targets, including TRIM59 and TBC1D9, which provide important clues for future scar treatment and prevention strategies.

Botulinum toxin type A inhibits the formation of hypertrophic scar through the JAK2/STAT3 pathway.

Hypertrophic scar (HS) is a fibrous proliferative disorder that occurs in the dermis after skin injury. Studies have confirmed that Botulinum toxin type A (BTA) is effective in scar prevention and treatment. However, the specific mechanism remains uncertain. Hypertrophic scar fibroblasts (HSFs) and normal skin fibroblasts (NSFs) from the skin tissues of HS patients were isolated and cultured. Western blot analysis was conducted to measure the expression of JAK2/STAT3 pathway-related proteins. HSFs were treated with the JAK2 inhibitor (AG490) or agonist (C-A1). The CCK-8 assay, EdU staining, scratch-wound assay and transwell assay were used to examine the biological properties of HSFs. Western blot, immunofluorescence, and Sirius red staining were used to assess the fibrosis of HSFs. Additionally, a mouse full-thickness wound model was constructed to investigate the role of BTA in wound healing. The results showed that the JAK2 and STAT3 phosphorylation levels were markedly increased in HS tissues and HSFs. AG490 treatment reduced cell viability, proliferation and migration capacity, and inhibited the fibrosis of HSFs, whereas C-A1 treatment had the opposite effect. BTA treatment inhibited the JAK2/STAT3 pathway. BTA reduced cell viability, proliferation and migration ability, and inhibited the fibrosis of HSFs, while C-A1 intervention weakened the impact of BTA. Meanwhile, BTA promoted wound healing and reduced collagen deposition in vivo. In conclusion, BTA inhibited the JAK2/STAT3 pathway, which in turn hindered the proliferation, migration and fibrosis of HSFs, and promoted wound healing in mice.

Platelet-rich plasma in dermatology and aesthetic medicine

Introduction and purpose Aesthetic medicine is one of the youngest fields of medicine. Initially, it focused on improving the quality of life of patients by using various treatments aimed at stopping the aging process. Over time, this branch of medicine has developed dynamically, and nowadays the treatments focus not only on improving the appearance of the skin and its defects, but are also used to treat many dermatological problems. Platelet-rich plasma (PRP) is an autologous concentrate of platelets in a small volume of plasma. having numerous applications in many fields of medicine. The aim of this work is to present the method, focusing on its positive effects in the problems of aesthetic and regenerative medicine, as well as in some dermatological diseases. Material and methods The review was baised on the articles obtained from Pubmed and Google Scholar scientific databases from recent years using the keywords: aesthetic medicine, platelet-rich plasma, dermatology. Results The presence of numerous growth factors and other active ingredients makes the action of PRP comprehensive and based on several mechanisms. Studies show a positive effect, especially in skin rejuvenation and anti-aging prevention, hair reconstruction, wound healing and reconstruction of scars of various etiologies, as well as in pigmentation disorders. Moreover, combining PRP with other methods such as laser therapy or microneedling produces a synergistic effect, improving overall treatment results. Conclusions Platelet-rich plasma is an autologous preparation obtained after centrifugation of blood collected from the patient. The properties of PRP make it widely used in many clinical situations. is used both in aesthetic medicine and in dermatological problems. It should be emphasized that further multi-center studies are needed to standardize treatment protocols and adapt them to specific problems. Keywords: aesthetic medicine, platelet-rich plasma, dermatology.

Comparative study on efficacy of benzoyl peroxide with adapalene versus plain adapalene in the treatment of acne vulgaris

BACKGROUND Acne vulgaris is a dermatological disorder of pilosebaceous unit, characterized by formation of comedones and inflammatory lesions. It is one of the most common skin manifestations among adolescents, also affecting the adult population. The treatment of acne basically involves reduction of lesions and prevention of permanent scarring. The current line of treatment for mild to moderate acne is topical medications with antimicrobials and retinoids. The present study assessed the efficacy of combination of adapalene and benzoyl peroxide in comparison to adapalene for topical treatment of mild to moderate acne vulgaris. OBJECTIVE The purpose of the study was to compare the clinical efficacy of topical adapalene and topical adapalene with benzoyl peroxide in treatment of mild to moderate cases of acne vulgaris. METHODOLOGY A prospective, comparative study was carried out among 84 patients with mild and moderate acne vulgaris visiting the Department of Dermatology, Kathmandu Medical College and Teaching Hospital, Bhaktapur, Nepal from December 2019 till March 2021. The patients fulfilling the inclusion criteria were divided into two groups. Group A received topical adapalene whereas Group B received topical adapalene with benzoyl peroxide. The efficacy of treatment in both groups were determined based on the reduction of total lesion count. Both inflammatory and non-inflammatory lesions were counted at 4th week, 8th week and 12th week. RESULTS All patients were assessed according to Global Acne Grading System (GAGS) and grouped as mild and moderate. The most frequent age group affected by acne vulgaris was 18-22 years. The mean age was 22.15 ± 5.315. Females (64.30%) were affected more commonly than males (35.7%). Majority of patients presented with moderate or inflammatory acne lesions. The face (90.5%) was most commonly affected site by acne vulgaris. The number of patients enrolled in the study were 84 out of which 63 (75%) completed the study. It was found that the reduction of non-inflammatory, inflammatory and total lesion count from the baseline were highly significant in between and both the group (P&lt;0.001). A total of 52.4% had very good result of the treatment, 44.4% of them had good result and remaining 3.2% of the patients’ result was fair. However, the efficacy of benzoyl peroxide with adapalene was found to be better than adapalene alone. CONCLUSIONThis study concluded that topical benzoyl peroxide with adapalene is more efficacious to treat mild to moderate acne vulgaris.

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) – Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions

BackgroundSevere cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. MethodsProspective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Resultswe report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). ConclusionIn the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registrationANZCTR ACTRN12619000241134. Registered 19 February 2019.

Current otolaryngologic applications of the novel self-assembling RADA-16 peptide matrix.

A novel bioresorbable agent on the market is PuraGel® (3-D Matrix, Tokyo, Japan), a RADA-16 product that acts as a synthetic hemostatic and space-filling gel that promotes wound healing and prevents adhesion formation. Given the reported benefits of accelerated wound healing and scar tissue prevention, there are multiple otolaryngologic applications where RADA-16 might improve outcomes. Our study highlights current utilization and associated post-operative complications with this product.

Targeting the Epigenome Reduces Keloid Fibroblast Cell Proliferation, Migration, and Invasion

Keloids are pathological fibroproliferative scars resulting from abnormal collagen deposition within and beyond the margins of the initial cutaneous insult. Keloids negatively impact quality of life functionally and cosmetically, with current treatment modalities unsatisfactory. Recent studies indicate that epigenetic dysregulation is central to the development and progression of keloids. Here we evaluate the functional significance of epigenetic targeting strategies in vitro using patient-derived keloid fibroblasts treated with small molecule inhibitors of HDACs, LSD1, CoREST and p300, as potential therapies for keloids. We find that both the dual-acting CoREST inhibitor, corin, and the HDAC inhibitor, entinostat, reduce fibroblast proliferation more than the LSD1 inhibitor, GSK-LSD1; additionally, corin was the most effective inhibitor of migration and invasion across keloid fibroblasts. RNA-seq analysis of keloid fibroblasts treated with corin demonstrates coordinate upregulation of many genes including key mediators of cell adhesion such as claudins. Corin also downregulates gene sets involved in cell cycle progression, including reduced expression of cyclins A1 and B2 compared to DMSO. These results highlight a significant role for epigenetic regulation of pathologic mediators of keloidal scarring and suggest that inhibitors of the epigenetic CoREST repressor complex may prove beneficial in the prevention and/or treatment of keloidal scarring in patients.

Alexis® Orthopedic Protector Provides Wound Protection and Aids in Hypertrophic Scar Prevention in Total Hip Arthroplasty.

Total hip arthroplasty (THA) is one of the most widely performed orthopedic surgeries. Techniques for small skin incisions and preservation of muscles and tendons have been developed. However, avoiding skin complications and muscle damage due to forced deployment and surgical manipulation is challenging. This study aimed to investigate whether the use of Alexis® Orthopedic Protector (Applied Medical Resources Corp., Rancho Santa Margarita, CA, USA) affects postoperative outcomes. This was a retrospective cohort study including 118 patients who underwent primary THA by the same surgeon at our single institution between March 2021 and March 2023. Protectors were used alternately for each operation. Fifty-nine patients were in the protector-using group (P group), and 59 were in the nonprotector-using group (N group), with comparisons made between groups. Protectors were placed under the fascia in all patients. Preoperative blood tests showed no difference in renal and hepatic function between the two groups. No differences in postoperative C-reactive protein (CRP) and creatine kinase (CK) values or in the Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ) and Numerical Rating Scale (NRS) scores were observed. Postoperative redness was significantly higher in the N group than in the P group (49.2% vs. 7%). The percentage of hypertrophic scars at three months postoperatively was 18.6% in the N group and 7% in the P group. Furthermore, the Japan Scar Workshop Scar Scale (JSS) indicated that hypertrophic scars were significantly worse in the N group than in the P group (p = 0.0012). Alexis® Orthopedic Protectors can not only provide short-term wound protection but also reduce the rate and degree of hypertrophic scarring.

Minimally invasive surgical approach to model hypertrophic scarring in the rabbit ear.

Current strategies for hypertrophic scar prevention and treatment are limited. To facilitate these efforts, a minimally invasive hypertrophic scar model was created in a rabbit ear for the first time based on previous methods used to induce ischemia. Six New Zealand white rabbits (12 ears total) were studied. First, ischemia was achieved by ligating the cranial artery, cranial vein and central artery, while preserving the caudal artery, caudal vein and central vein, respectively. The relative level of ischemia induced at time of surgery, both baseline and maximum perfusion, was assessed with a fluorescent light-assisted angiography and demonstrated lower rates of perfusion in the ischemic ears. Following vascular injury, a 2-cm full thickness linear wound was created on the ventral ear and closed with 4 - 0 Nylon sutures under high tension. For each rabbit, one ear received a combination of ischemia and wounding with suture tension (n = 6), while the other ear was non-ischemic with wounding and suture tension alone (n = 6). Four weeks post-operatively, ischemic ears developed scar hypertrophy (histological scar thickness: 1.1 ± 0.2mm versus 0.5 ± 0.1mm, p < 0.05). Herein, we describe a novel, prototypical minimally invasive rabbit ear model of hypertrophic scar formation that can allow investigation of new drugs for scar prevention.

The Efficacy of Onion Extract on the Prevention or Treatment of Scars: A Systemic Review.

Scars are common and debilitating outcomes of burn injury, with no current consensus regarding the gold standard in scar management. Non-invasive interventions such as silicone gels are popular adjuvant treatments due to ease of application. Onion extract (OE) has been proposed as a potential scar treatment modality due to its anti-microbial and anti-inflammatory properties. A systematic search of the literature was conducted using PubMed, Scopus, and Cochrane for articles published between January 2000 and December 2021. Inclusion criteria were studies: (a) involved OE gel or OE treatment, and (b) those assessing scar prevention or treatment outcomes. Patient and physician reported scar outcomes after treatment and adverse effects were recorded. A total of 21 articles were included in the final review. Five studies found statistically significant improvements in overall scores and individual VSS components in the OE treatment group compared to the silicone groups. Several studies found combined treatment of OE with other topical treatment modalities such as triamcinolone or silicone gel produced significant improvements in scar symptoms. In this review, reported adverse effects were minimal, often consisting of self-resolving pruritus, irritation, and erythema. This review supports OE's potential utility in scar prevention and treatment. Most studies reported minimal adverse events with OE application and significant benefits in specific scar characteristics. Further research is needed to investigate scar outcomes after treatment with OE with larger sample sizes and a follow up period greater than a year.

SHH induces macrophage oxidative phosphorylation and efferocytosis to promote scar formation

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.

Early topical mitomycin-C prevents stricture formation in children with caustic ingestion.

Stricture formation is the most common remote complication of caustic ingestion. The aim of this study was evaluation of the efficacy of early topical endoscopic application of mitomycin C (MMC) in prevention of stricture formation after corrosive ingestion in children. We enrolled 78 children with a history of caustic ingestion within 48 h in a prospective, randomised-controlled study. Only 61 children completed the study and were classified into two groups: group A and B. After initial stabilisation, patients in group A (n = 30) received topical application of MMC within the initial 48 h while patients in group B (n = 31) only received conventional management. Follow-up endoscopic dilatation was done every 2 weeks to patients in either group until no need for further dilatation. The barium study, which was done on the third week, revealed that all the patients (100%) on conservative management (group B) had strictures while only nine patients (30%) in group A had strictures (P < 0.001). The median number of dilatations required for patients in group B was 26 (min. = 23 and max. = 32) while in group A, it was 0 (min. = 0 and max. = 7) (P < 0.001). The success of early MMC application was complete response in 26 patients (86.7%), partial response in 3 patients (10%) and no response in 1 patient (3.3%). On the other side, conventional therapy with endoscopic dilatation achieved complete response in 11 patients (35.5%). Early topical MMC application proved its efficacy and safety in prevention of scar and stricture formation in children following caustic ingestion.