Treatment Of Hypertrophic Scars Research Articles

Comparative study of efficacy of intense pulsed light versus Intralesional triamcinolone in the treatment of hypertrophic scars and keloids

Keloids and hypertrophic scars are hyperproliferative response of dermal connective tissue to trauma. Their management remains a challenge for practitioners as there is still no universally accepted treatment, leading to recurrences which are frustrating for patients and clinicians alike. Hence, it becomes essential to determine a modality with highest efficacy, least recurrence and better patient compliance.To compare the therapeutic effectiveness of Intralesional triamcinolone acetonide versus Intense pulsed light for treatment of keloids and hypertrophic scars.A single centre, cross-sectional study was conducted on 60 patients. Patients were randomly allocated in two groups, group one received Intralesional steroids ( ILS)-triamcinolone acetonide and group two was treated by Intense pulsed light(IPL).Both groups were accessed for improvement every 15 days until 5 sessions were complete.Both study groups showed significant changes after treatment. Patients treated with ILS showed greater reduction in height. IPL group showed significant reduction in vascularity . Pigmentary outcomes were more favourable with IPL, whereas with ILS hypopigmentation was noted as a common side effect. Both groups showed significant reduction in pliability.Both regimens showed excellent responses with minimum recurrence rates, indicating their high efficacy in management of keloids and hypertrophic scars.

Discussion of the Most Effective Scar Treatment Methods

Scars are a natural consequence of the wound healing process, but excessive scarring can lead to aesthetic and functional concerns. This paper aims to review current scar treatment methods, including modern techniques such as laser therapies, microneedling, corticosteroid injections, and silicone dressings. Special attention is given to the treatment of hypertrophic scars and keloids, which present significant challenges in contemporary medicine. An analysis of recent studies highlights the effectiveness of these methods in improving scar appearance and reducing discomfort associated with scars. Additionally, emerging experimental therapies, such as the use of stem cells and monoclonal antibody treatments, are discussed. The findings suggest that early intervention and individualized treatment approaches are crucial for achieving optimal aesthetic and functional outcomes.

The Role of Extracorporeal Shock Wave Therapy in Keloids and Hypertrophic Scars: A Systematic Review.

Keloids and hypertrophic scars are pathological scars that result from a prolonged and aberrant response to wound healing, resulting in raised and thickened skin lesions. Traditional treatments include occlusive dressings, compression therapy, intralesional steroids, and surgical excision with refashioning. Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment method that employs mechanotransduction to stimulate a biological cascade resulting in tissue regeneration. This review aims to explore the literature for published evidence on the role of ESWT in the treatment of keloids and hypertrophic scars. A literature search following the PRISMA guidelines was conducted on PUBMED, Google Scholar, and the Cochrane Database of Systematic Reviews, for studies demonstrating the use of ESWT in keloids and hypertrophic scars. From this, 79 articles were identified, 12 of which met the eligibility criteria and were thus analyzed and included in the study. As monotherapy for keloids, ESWT showed comparable improvements in functional and aesthetic outcomes compared to traditional intralesional steroid therapy. Keloids treated with combination therapy of ESWT with intralesional steroids had better outcomes than those treated with intralesional steroids alone. Improvements in hypertrophic scar cosmesis, discomfort, and function with the use of ESWT were reported. Histologic improvements such as decreased collagen content, reduction of fibrotic markers, and fibrogenic cytokines were also described. ESWT is a promising treatment modality for pathological scars, offering comparable outcomes to traditional therapies with added benefits such as non-invasiveness. Further research is warranted to establish optimal protocols and its role in pathological scar management.

The Efficacy of Botulinum Toxin Type A (BTA) in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Hypertrophic scars cause significant physical and emotional discomfort. Botulinum toxin type A (BTA) has shown promising outcomes in reducing scar formation. Research suggested its effectiveness in managing hypertrophic scars and keloids. This systematic review and meta-analysis were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled trials (RCTs). The included studies involved patients with hypertrophic scars treated with BTA. Five databases were searched from inception to August 2024. Studies were screened and selected by two independent reviewers.Data on study design, patient demographics, and interventions was extracted. The risk of bias (ROB) was assessed using the ROB revised tool developed by Cochrane (ROB2). Meta-analysis was performed using RevMan Web (The Cochrane Collaboration, London, UK) with a random-effects model due to high heterogeneity, calculating mean differences for the primary and secondary outcomes. Outcomes included VancouverScar Scale (VSS) scores, scar thickness, vascularity, pliability, and pigmentation. The systematic review identified 182 records from five databases. The screening process resulted in seven studies included in the final analysis after assessment for eligibility. The efficacy of BTA in treating hypertrophic scars and keloids was assessed. The meta-analysis showed that BTA significantly improved VSS scores, with a pooled mean difference of -1.69 (P = 0.01). However, BTA did not show a statistically significant effect on reducing scar height/thickness or improving vascularity. Scar pliability was significantly improved by BTA, with a pooled mean difference of -0.76 (P = 0.002), while there was no significant effect on pigmentation. High heterogeneity was observed across the studies. BTA could be used as an effective treatment for the components of hypertrophic scars and keloids, especially regarding their pliability and improving scar quality. However, for functions such as the change in scar height, vascularity, and pigmentation, more research is still required among larger RCTs. Future research should focus on refining the treatment regimens and the mode of action of BTA to the scar tissue.

Recovery in patients undergoing ablative fractional carbon dioxide laser for adult hypertrophic burn scars: a longitudinal cohort study

IntroductionAblative fractional carbon dioxide laser (AFCO2L) is widely used as a treatment for hypertrophic burn scars. This study aimed to evaluate clinician and patient-reported outcomes after AFCO2L treatment, safety, and identify factors influencing outcomes. MethodsThis longitudinal study recruited adult patients with hypertrophic burn scars treated with AFCO2L at a single Australian burn unit. Patients received up to four AFCO2L treatments over approximately 12 months. Outcomes were ultrasound scar thickness, the Patient and Observer Scar Assessment Scale (POSAS), and the Brisbane Burn Scar Impact Scale (BBSIP), measured at baseline and 3, 6, and 12-months post first AFCO2L treatment. Analysis used mixed effects linear models. Results47 patients were included with median age 32 years (IQR:24,53) and median burn TBSA of 35% (IQR:7.5%,48%). Statistically significant improvements between baseline and 12-month follow-up occurred in scar thickness, all POSAS and BBSIP subscores. Most improvements remained when accounting for TBSA, Fitzpatrick skin type, scar maturity, and body area treated. Patients reported transient symptoms after 61 of 89 (69%) AFCO2L treatments, but infection or delayed wound healing occurred after only 4 of 89 (4%) treatments. ConclusionThis study supports safety and improved clinician and patient-reported outcomes in patients undergoing AFCO2L for hypertrophic burn scars.

Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis.

Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. 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 .

Losartan in Situ Forming Gel as a New Treatment for Hypertrophic Scars.

Hypertrophic scars are defined as visible lesions formed by excessive wound healing that cause cosmetic and, in some cases, functional challenges in patients. This study aimed to assess the efficacy of intralesional injections of losartan-loaded in situ forming gel and compare it with the common treatment (triamcinolone) in preventing scar formation. The formulation was prepared using a thermosensitive PLGA-PEG-PLGA triblock copolymer. Ear scar tissue in rabbits represented the hypertrophic scar, and the animals were treated with three treatments in three groups. Nine weeks following the single treatment, images of the scars were obtained and quantitatively analyzed using ImageJ and light microscopy was used to evaluate the fibroblast cell number, vascularization, inflammation and collagen deposition and fibrosis in H&E-stained sample tissue. According to the results based on the ImageJ and the Vancouver criteria, the losartan in situ forming gel (F-LG) indicated significantly higher improving effects on decreased vascularity and pigmentation in comparison with triamcinolone (F-TA) and placebo as a control (F-Ctl), although the effect F-LG was almost similar to F-TA on pliability and scar height, and they were better than the control. Histological findings showed F-LG and F-TA have less inflammatory and fibroblast cells compared to F-Ctl. Also, results indicated the dermal layers of the F-TA and F-LG groups' scar were thinner, and the deposition of collagens was reduced compared to the control. Consequently, F-LG was found to be an effective treatment in reducing scarring and promoting wound healing.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Oregano essential oil-infused mucin microneedle patch for the treatment of hypertrophic scar

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-β1 (TGF-β1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally.

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.

Impact of dual wavelength laser therapies in the treatment of hypertrophic scars and keloids: a systematic review

Impact of dual wavelength laser therapies in the treatment of hypertrophic scars and keloids: a systematic review

Adipose-derived mesenchymal stem cells suppress fibroblast proliferation of hypertrophic scar through CCL5 and CXCL12.

Adipose-derived mesenchymal stem cells (ADSCs) can accelerate wound healing, reduce scar formation, and inhibit hypertrophic scar (HTS). ADSCs can secrete a large amount of CCL5, and CCL5 has been proved to be pro-inflammatory and pro-fibrotic. CXCL12 (SDF-1) is a key chemokine that promotes stem cell migration and survival. Therefore, this study selected normal skin and HTS conditioned medium to simulate different microenvironments, and analyzed the effects of different microenvironments on the expression of CCL5 and CXCL12 in human ADSCs (hADSCs). hADSCs with silenced expression of CCL5 and CXCL12 were co-cultured with hypertrophic scar fibroblasts to verify the effects of CCL5 and CXCL12 in hADSCs on the proliferation ability of hypertrophic scar fibroblasts. A mouse model of hypertrophic scar was established to further confirm the effect of CCL5 and CXCL12 in hADSCs on hypertrophic scar formation. CCL5 level was found to be significantly high in hADSCs cultured in HTS conditioned medium. CXCL12 in HTS group was prominently lowly expressed compared with the normal group. Inhibition of CCL5 in hADSCs enhanced the effects of untreated hADSCs on proliferation of HTS fibroblasts while CXCL12 knockdown exerted the opposite function. Inhibition of CCL5 in hADSCs increased the percentage of HTS fibroblasts in the G0/G1 phase while down-regulation of CXCL12 decreased those. Meanwhile, the down-regulated levels of fibroblast markers including collagen I, collagen III, and α-SMA induced by CCL5 knockdown were significantly up-regulated by CXCL12 inhibition. hADSCs alleviate the HTS of mice through CCL5 and CXCL12. In summary, our results demonstrated that hADSCs efficiently cured HTS by suppressing proliferation of HTS fibroblasts, which may be related to the inhibition of CXCL12 and elevation of CCL5 in hADSCs, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of HTS.

Prophylactic Antibiotics are Unnecessary for Routine CO2 Laser Burn Scar Treatment.

CO2 ablative fractional laser (CO2 AFL) therapy is a safe and effective procedure when used in the treatment of hypertrophic scars for burn patients. It has a high patient satisfaction rate and a minimal side effect profile, typically consisting of postoperative pain, irritation, surgical site inflammation, and, in rare cases, infection. Although prophylactic antibiotics have historically been recommended, there is a paucity of literature on the topic and recent studies indicate that they may be unnecessary in routine cases. In this retrospective, single center descriptive study, 230 cases in patients with hypertrophic burn scars treated with CO2 AFL therapy were compared. 28 cases were with the use of prophylactic antibiotics and 201 cases were without the use of prophylactic antibiotics. We found that there was no significant association between the use of antibiotics and the prevention of topical skin infection in cases treated with CO2 AFL therapy (p=1). Therefore, we conclude that the omission of prophylactic antibiotics is not associated with an increased risk of infection and recommend that prophylactic antibiotics should not be indicated in the setting of routine CO2 AFL therapy for patients with hypertrophic burn scars.

Graphene Quantum Dots Reduce Hypertrophic Scar by Inducing Myofibroblasts To Be a Quiescent State.

Contrary to the initial belief that myofibroblasts are terminally differentiated cells, myofibroblasts have now been widely recognized as an activation state that is reversible. Therefore, strategies targeting myofibroblast to be a quiescent state may be an effective way for antihypertrophic scar therapy. Graphene quantum dots (GQDs), a novel zero-dimensional and carbon-based nanomaterial, have recently garnered significant interest in nanobiomedicine, owing to their excellent biocompatibility, tunable photoluminescence, and superior physiological stability. Although multiple nanoparticles have been used to alleviate hypertrophic scars, a GQD-based therapy has not been reported. Our in vivo studies showed that GQDs exhibited significant antiscar efficacy, with scar appearance improvement, collagen reduction and rearrangement, and inhibition of myofibroblast overproliferation. Further in vitro experiments revealed that GQDs inhibited α-SMA expression, collagen synthesis, and cell proliferation and migration, inducing myofibroblasts to become quiescent fibroblasts. Mechanistic studies have demonstrated that the effect of GQDs on myofibroblast proliferation blocked cell cycle progression by disrupting the cyclin-CDK-E2F axis. This study suggests that GQDs, which promote myofibroblast-to-fibroblast transition, could be a novel antiscar nanomedicine for the treatment of hypertrophic scars and other types of pathological fibrosis.

Antihypertrophic Scar Effect of Iraqi Plantago major Extracts

Background: Plantago major, historically renowned for its medicinal attributes across diverse cultures, has recently been under the research spotlight for its antihypertrophic scar effects. Aim: To investigate the efficacy of Plantago major extracts in the treatment of hypertrophic scars, particularly comparing the effects of methanol and ethyl acetate extracts. Methodology: Samples of the plant, procured from Baghdad's Al-Salihiya Neighbourhood in November 2021, underwent authentication at the Iraqi local Herbarium in the Al-Razi centre for alternative medicine. Using the Soxhlet apparatus, the dried plant material was extracted with methanol and subsequently partitioned with ethyl acetate. Both the ethyl acetate and methanol extracts were later formulated into ointments. Results: The ointments were tested on hypertrophic scars induced in rats. Three groups of 12 rats each were used—ethyl acetate, methanol, and a control group using only Vaseline. Both extracts demonstrated efficacy in reducing scars, with the methanol extract showing more pronounced results. Conclusion: The methanol extract displayed superior outcomes, potentially attributable to its richer phytochemical content compared to the ethyl acetate extract.

First results of laser treatment in our pediatric burn patients

Objectives: This study aimed to share the first results of the laser application we started using in our center to treat hypertrophic scars formed after burns. Patients and methods: The retrospective study was conducted with 10 pediatric patients (5 males, 5 females; median age: 3.5 years; range, 30 month to 10 years) treated for post-burn hypertrophic scars between January 2023 and July 2023. Burn patients to whom we applied Nd:YAG (neodymium:yttrium aluminum garnet) laser due to complaints such as contracture, hypertrophic scar, and itching were evaluated. Of all patients who underwent laser application, some received intralesional steroid application during the same session. The patient's age, sex, burn agent, burn percentage, scar areas, number of sessions, post-laser complaints, findings, the patient scar assessment scale (PSAS), and the observer scar assessment scale (OSAS) were evaluated. Results: The burn agent was two flame burns and eight scald burns. A graft was not applied in four patients, and a graft was used in six patients. The time between the burn dates and laser application ranged between seven months and eight years. One patient underwent four laser sessions, one patient had three laser sessions, and the other patients underwent one session. It was observed in the controls that after laser application, the itching decreased significantly, the hypertrophic scar softened, and its color faded. The PSAS and OSAS scores were found to be statistically significantly reduced (p&lt; 0.01). Conclusion: In the treatment of post-burn hypertrophic scars with Nd:YAG laser treatment, the hypertrophic scar softens, its color fades, itching decreases significantly, and there is a decrease in contracture. Treatment satisfaction of patients and parents had a positive psychological impact on the family. Furthermore, laser therapy can reduce the cost of expensive post-burn care. The increasing use of laser applications also reveals the need for standardization.

Increased Patient Compliance with Silicone Gel Sheeting and Topical Silicone Gel for Hypertrophic Scar Improves Scar Outcomes

Background: Although silicone-based products are widely used for hypertrophic scar (HS) treatment, limited research exists on the correlation between patient compliance of silicone products and scar outcomes. This study aims to investigate whether continuous and consistent use of topical silicone gel (TSG) and silicone gel sheet (SGS) improves scar characteristics and whether patient compliance influences scar outcomes.Methods: A total of 79 patients with HS were randomized into either TSG (n=38) or SGS group (n=41) by an independent physician who had not seen the patients. Patient compliance was assessed based on application frequency and duration. Patients were divided into three subgroups according to compliance. Scar characteristics were evaluated using the Vancouver Scar Scale (VSS) and patient self-assessment via a visual analogue scale (VAS) for 6 months.Results: VSS pigmentation and scar height worsened in patients who applied silicone products for less than 3 days per week, especially in the TSG group. Patients who applied silicone products for more than 4 days per week showed significant improvements in all factors. Patients reported improvements in VAS scar height, pigmentation, and hardness as application time increased. Pain and itching improved regardless of application time.Conclusion: Continuous and consistent use of TSG and SGS improved HS outcomes. Applying silicone products more than 4 days in a week correlated with better scar characteristics, except pain and itching. Applying silicone products less than 3 days in a week is not recommended, as this may worsen scar height and pigmentation.

Evaluation of Silicone-Based Gel for the Treatment of Hypertrophic Scarring in Rat Models

Background: Hypertrophic scarring represents an aberrant response to wounds in certain individuals, manifesting with symptoms such as itching, tenderness, pain, and pigmentation. This study aimed to investigate the impact of a silicone-based gel on the healing of hypertrophic scars, particularly those originating from deep tissue wounds.Methods: A rat model of wound healing and scarring was established, and 12 rats were randomly assigned to three groups: Dermatix Ultra group, SFG-100 silicone-gel group, and non-treated group. Rats in the treated groups (Dermatix Ultra and SFG-100 silicone-gel) received twice-daily applications for 8 weeks. Histologic analysis, including biopsy, was conducted to evaluate the scar elevation index, epidermis thickness, and the number of granulation veins.Results: Overall, both the Dermatix Ultra and SFG-100 silicone-gel groups exhibited improvements in hypertrophic scar healing, accompanied by a significant reduction in skin pigmentation. Histopathologically, scars in both treated groups displayed a notable decrease in scar elevation index, epithelial thickness, and collagen disorganization compared to the non-treated group. However, no significant difference was observed between the Dermatix Ultra and SFG-100 silicone-gel groups.Conclusion: The results suggest that SFG-100 silicone-gel is an effective therapeutic agent for hypertrophic scars. Further research is warranted to elucidate the mechanisms underlying its efficacy and to optimize its application for clinical use.

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.

CD248 interacts with ECM to promote hypertrophic scar formation and development

Hypertrophic scar (HS) presents a significant clinical challenge, frequently arising as a fibrotic sequela of burn injuries and trauma. Characterized by the aberrant activation and proliferation of myofibroblasts, HS lacks a targeted therapeutic approach to effectively reduce this dysregulation. This study offers novel evidence of upregulated expression of CD248 in HS tissues compared to normal skin (NS) tissues. Specifically, the expression of CD248 was predominantly localized to α-SMA+-myofibroblasts in the dermis. To explain the functional role of CD248 in dermal myofibroblast activity, we employed a targeted anti-CD248 antibody, IgG78. Both CD248 intervention and IgG78 treatment effectively suppressed the proliferative, migratory, and ECM-synthesizing activities of myofibroblasts isolated from HS dermis. In addition, IgG78 administration significantly attenuated HS formation in an in vivo rabbit ear model. The LC/MS analysis coupled with co-immunoprecipitation of HS tissues indicated a direct interaction between CD248 and the ECM components Fibronectin (FN) and Collagen I (COL I). These findings collectively suggest that CD248 may function as a pro-fibrotic factor in HS development through its interaction with ECM constituents. The utilization of an anti-CD248 antibody, such as IgG78, represents a promising novel therapeutic strategy for the treatment of HS.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

BACKGROUND Hypertrophic scar (HTS) is dermal fibroproliferative disorder, which may cause physiological and psychological problems. Currently, the potential mechanism of WuFuYin (WFY) in the treatment of HTS remained to be elucidated. AIM To explore the potential mechanism of WFY in treating HTS. METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HTS-related genes were obtained from the GeneCards, DisGeNET, and National Center for Biotechnology Information. The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analysis. A protein + IBM-protein interaction (PPI) network was developed using STRING database and Cytoscape. To confirm the high affinity between compounds and targets, molecular docking was performed. RESULTS A total of 65 core genes, which were both related to compounds and HTS, were selected from multiple databases. PPI analysis showed that CKD2 , ABCC1 , MMP2 , MMP9 , glycogen synthase kinase 3 beta (GSK3B ), PRARG , MMP3 , and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG ) were the hub targets and MOL004941, MOL004935, MOL004866, MOL004993, and MOL004989 were the key compounds of WFY against HTS. The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway. Moreover, by performing molecular docking, we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity. CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941, MOL004989, and MOL004993 were the main compounds of WFY in HTS treatment.