Purpose: Keloid tissue represents an abnormal proliferation of fibroblasts, typically resulting from skin injury. These lesions can lead to significant physiological dysfunction and aesthetic concerns, particularly when located on the face. Traditional treatments, such as intralesional injections, laser therapy, and surgical excision, have shown limited efficacy and are associated with high recurrence rates.

Materials and methods: In a recent case, a 19-year-old male with a keloid on the upper lip did not respond to local injections of triamcinolone acetonide (TAC) or carbon dioxide ablative fractional resurfacing laser therapy.

Results: A combined treatment approach involving trepanation and superficial radiotherapy successfully flattened the keloid tissue, with no recurrence observed during a 3-year follow-up period.

Conclusions: This case underscores the potential efficiency and safety of combined therapeutic interventions and contributes valuable evidence towards the development of novel treatment strategies for keloids.

Keloids are benign fibroproliferative skin scars that expand beyond the original wound site. Hypoxia and angiogenesis are thought to drive pathological scar formation in keloids. We utilized biopsies collected before, during and after the double-blinded randomized controlled trial (RCT) comparing the intralesional treatments of 5-fluorouracil and triamcinolone injections in 48 human keloids. We could not detect any cells expressing the hypoxia markers (carbonic anhydrase 9 and hypoxia-inducible factor 1α) in the three distinct regions of keloid dermis. The amount of epidermal hypoxia could not predict the response to treatment. The middle dermis of the patients obtaining a clinical response to the intralesional injections showed significant increase in mature blood vessels and in lymphatics after the treatment. Our study does not support hypoxia being the driver behind keloid formation but demonstrates that the patients obtaining a response to intralesional therapies develop more blood vessels and lymphatics in the middle dermis of the keloids during the treatment.

The Modified Buried Vertical Mattress Suture (MBVMS) has demonstrated potential in mitigating postoperative incision scar hyperplasia. This study aimed to retrospectively evaluate the efficacy of combining MBVMS with tension-reducing tape in minimizing scar formation following forearm tattoo resection.

A total of 46 patients undergoing forearm tattoo resection or partial resection were included. Participants were stratified into two cohorts: a control group (n = 17) receiving traditional intradermal sutures and a research group (n = 29) treated with MBVMS combined with tension-reducing tape. Scar width was measured at predefined intervals (3, 6, and 12 months postoperatively). Scar hyperplasia was assessed using the Observer Scar Assessment Scale (OSAS) and Patient Scar Assessment Scale (PSAS).

Both groups exhibited initial scar widening between 3 and 6 months postoperatively, followed by gradual narrowing from 6 to 12 months. However, the research group demonstrated significantly reduced scar width at all time points compared to the control group (p < 0.05). Similarly, OSAS and PSAS scores were consistently lower in the research group (p < 0.05), indicating superior cosmetic and patient-reported outcomes.

These findings suggest that MBVMS combined with tension-reducing tape effectively reduces scar hyperplasia in forearm tattoo resection, offering a promising approach for improving postoperative aesthetic outcomes.

Salidroside, a natural herb, exerts considerable anti-tumor effects in various human cancers. Evidence unveils that Salidroside mediates gene expression to affect cancer progression. Our work intended to uncover the molecular mechanism of Salidroside functional role in keloid. Expression analysis for JAG1 and miR-26a-5p in tissues and cells was performed using qRT-PCR or western blotting. For functional analysis, cell proliferation, apoptosis and migration were ascertained by CCK-8, flow cytometry and Transwell assay, respectively. The putative binding relationship between JAG1 and miR-26a-5p was further confirmed by dual-luciferase reporter assay. Salidroside exerted pharmacological properties in keloid and impaired keloid fibroblast (KF) viability. JAG1 was upregulated in keloid tissues, and its expression was repressed by Salidroside in KFs. Salidroside depleted KF proliferation and migration but stimulated apoptosis, and JAG1 knockdown largely strengthened the functional effects of Salidroside. MiR-26a-5p interacted with JAG1 3'UTR and expressed with an opposite pattern with JAG1 in keloid. Inhibition of miR-26a-5p largely abolished the effects of JAG1 knockdown in Salidroside-treated KFs, leading to the recovery of KF aggressive behaviors. Salidroside blocked KF aggressive progression by upregulating miR-26a-5p to inhibit JAG1, which provided evidence on the anti-tumor effects of Salidroside in human keloid.

Hypertrophic scar (HS) is a common fibrotic disease primarily caused by excessive activation and proliferation of fibroblasts. Dioscin, a steroidal saponin isolated from the roots of Dioscorea plants, has been shown to be effective in the management of metabolic disorders, regulation of inflammation, and inhibition of tumor growth. This study investigates the inhibitory effects of Dioscin on the proliferation and functionality of human scar fibroblasts (HSFs) and its therapeutic potential for HS, as well as the underlying mechanisms involved. The impact of Dioscin on collagen secretion and HSF activation was assessed using quantitative real-time PCR (RT-qPCR) and Western blot (WB). HSF functionality was evaluated through EdU proliferation, wound healing, transwell migration, and contracture assays. RNA sequencing revealed that Dioscin triggers HSF apoptosis and ferroptosis by compromising mitochondrial membrane potential. Immunofluorescence and WB were employed to examine the mechanisms of Dioscin-induced apoptosis and ferroptosis. The therapeutic efficacy of Dioscin was further assessed in vivo using a rabbit ear scar model. Results show that Dioscin suppresses HSF proliferation, migration, and contraction, reduces collagen secretion, and deactivates HSFs by destabilizing mitochondrial membrane potential, leading to ROS accumulation. Local administration of Dioscin significantly mitigates scar formation in rabbit ears. In conclusion, Dioscin reduces HS progression by disrupting mitochondrial membrane potential, inducing oxidative stress, and promoting apoptosis and ferroptosis in HSFs, highlighting its potential as a therapeutic agent for HS.

Skin diseases encompass a diverse range of conditions with significant psychological and physiological impacts. N6-methyladenosine (m6A) RNA methylation is a key epitranscriptomic modification that regulates gene expression by influencing RNA stability, splicing, translation, export and degradation. Recent studies have highlighted the crucial role of m6A modification in the pathogenesis and progression of various skin diseases. m6A modification affects critical biologic processes of the skin, such as inflammation, immune response and cellular ageing. This review systematically explores the landscape of m6A modification in nontumour skin diseases, elucidating its regulatory roles and therapeutic implications, including wound healing, scar and keloid, skin ageing, psoriasis, systemic lupus erythematosus, acne vulgaris, rosacea, chronic actinic dermatitis and scleroderma. The intricate mechanisms of m6A modification can lead to the development of novel diagnostic biomarkers and therapeutic strategies, ultimately improving patient outcomes.

Keloid is a special type of scar considered prototypic of skin fibrosis. Unlike hypertrophic scars, keloids exceed the margins of the original wound, and exist over time without a quiescent or regressive phase. Although keloids do not metastasize, they exhibit tumor-like characteristics, and share many similarities. Large epidemiological study demonstrates that patients with keloids have a 1.49-fold higher risk for cancers. Keloids can lead to severe functional impairments and diminish quality of life which increases hidden costs for patients and medical systems. The main goals of treatments are to improve scar appearance, symptoms and patient's quality of life (QoL). However, the microenvironment, pathogenesis, formation and development of the keloid are complex, the efficacy of multiple treatments were limited. Therefore, this up-to-date review aimed to target the current concepts in keloid treatment and differential diagnosis. The goal is to provide a reference for doctors and researchers to improve the accuracy of diagnosis and facilitate the selection of personalized treatment methods for patients with keloids.

Hypertrophic scar (HTS) is a prevalent chronic inflammatory skin disorder characterized by abnormal proliferation and extracellular matrix deposition. N-Myc downstream regulated gene 2 (Ndrg2) is a cell stress response gene related to cell proliferation, differentiation and various fibrotic diseases. However, the role of Ndrg2 in HTS is unknown and warrants further investigation. In this study, we confirmed that the expression of Ndrg2 was increased in HTS of human and a bleomycin-induced fibrosis mouse model. We then used Ndrg2 knockout mice and found Ndrg2 deletion could significantly reduce the synthesis of collagen and alleviate skin fibrosis. In addition, the proliferation and migration of Ndrg2-interfered HTS-derived fibroblasts decreased and those of Ndrg2-overexpressed normal skin-derived fibroblasts increased. Further, by western blot analysis, we verified that the expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT and AKT were all increased after Ndrg2 overexpressed in normal skin-derived fibroblasts. Moreover, PI3K inhibitor (LY294002) administration significantly rescued the effect of Ndrg2 overexpression on skin fibrosis. In summary, our results demonstrated that Ndrg2 could promote HTS fibrosis by mediating PI3K/AKT signaling pathway. Our data suggest that Ndrg2 may be a promising therapeutic target for HTS.

Auricular keloids may be associated with social stigma and impair patients' quality of life (QoL) significantly. Little is known about the effect of different therapeutic concepts on the patient's QoL. This study aims to investigate the QoL in patients with auricular keloids undergoing a specific multimodal therapeutic regimen.

Patients suffering from auricular keloids were treated by a multimodal treatment comprising surgical excision, intralesional triamcinolone acetonide, and subsequent application of customized magnetic pressure splints. A prospective assessment of QoL was conducted using the validated Keloid Intervention Benefit Inventory-21 questionnaire at three time points.

In total, 22 auricular keloids were included in our study. All patients completed a comprehensive 1-year follow-up assessment, with an average follow-up duration of 29 months post-surgery. Quantitative analysis of QoL metrics demonstrated significant improvement of QoL at the three times of measurement (P < .0001). Significant results were also found for the subcategories general health, physical health, social interaction, and self-esteem.

This study underscores the necessity of assessment of QoL in keloid treatment. Our findings highlight the advantages of multimodal treatment in enhancing patients' QoL throughout the treatment period and managing auricular keloids with low recurrence.

The study was registered at the German Clinical Trials Register (Register ID: DRKS00016348, https://drks.de/search/en/trial/DRKS00016348).

Objective: Fibroblasts (FBs) are the cytological basis of keloid (KD) formation. This study aimed to identify the key pathogenic target cell subpopulation involved in KD recurrence. Approach: Single-cell RNA sequencing data were retrieved from public databases, revealing distinct gene expression patterns in FB subpopulations. Flow cytometry (FCM) was used to identify the surface molecular phenotypes of FBs that affect KD recurrence. Simultaneously, logistic regression analysis was performed to assess the predictive value of changes in FB subpopulation percentages for clinical KD recurrence. Results: The percentage of keloid fibroblasts was significantly greater than that in normal tissues. Through further clustering analysis of the FB population, we obtained four subpopulations, FB1-FB4, in which the percentages of FB1 subpopulation were increased, and functional enrichment analysis suggested that the FB1 subpopulation may play a greater role in extracellular matrix collagen oversynthesis in KD. In addition, the gene expression of CD26 (DPP4), CD117 (c-KIT), and CD34 in the FB1 subpopulation was significantly higher than that in FB2-4 subpopulations. Moreover, the percentage of CD26+/CD117+/CD34+ cell subpopulations in the FCM data of patients with KD recurrence was significantly increased. Regression analysis confirmed that the CD26+/CD117+/CD34+ FB subpopulation was a risk factor for relapse. Innovation: We demonstrated that the molecular phenotypic and functional heterogeneity of FBs influences KD recurrence. Conclusion: We identified key pathogenic FB subpopulations that may affect KD development, which can be used as potential markers to predict recurrence and provide potential target cell populations for future clinical treatment.

To evaluate and compare the postoperative scarring with nasolabial flap reconstruction using silicone gel versus silicone gel sheet.

This was an in vivo comparative study carried out in the Department of Oral and Maxillofacial Surgery. 10 patients who fit into the inclusion criteria were selected. The surgical procedure was carried out as per the standard protocol. The fishbowl method was used to allocate groups, group A where silicone gel application was prescribed and group B where silicone gel sheets were applied. On postoperative day 10, sutures were removed and the modality was advised as per the study protocol. In group A, silicone gel application was prescribed twice daily for 3 months. In group B, silicone gel sheet application was prescribed for 4 hours on day 1, increasing it by 2 hours a day till 1 week and then 24 hourly until 3 months. The patients were evaluated by a second investigator every 2 weeks until 3 months and at the end of 6 months. The healing of scars was evaluated as per the Vancouver Scar Scale.

Silicone gel showed superior results than silicone gel sheet statistically in terms of pigmentation, vascularity, height and pliability (p<0.05).

In our study, we found an appreciable difference in the healing of scars in both groups. Although both methods aid in better healing of nasolabial scars, silicone gel offers better healing and is well tolerated by the patients.

Hypertrophic scars and keloids are human cutaneous fibroproliferative conditions that develop after burns, trauma, surgery, and inflammation. Vitamin D inhibits keloid fibroblast proliferation by reducing TGF-β-induced extracellular matrix formation, boosting matrix metalloproteinase activity, and reducing inflammation.

To study the effect of intralesional and systemic Vitamin D3 injection on hypertrophic scars and keloids and whether vitamin D3 deficiency increases scarring.

This study included 30 hypertrophic scars and keloid patients divided into groups depending on serum vitamin D levels. Every patient was tested for vitamin D using ELISA. Group I: patients with vitamin D deficiency or insufficiency received a systemic injection of vitamin D (cholecalciferol 200 000 I.U.) once monthly for 3 months with a calcium oral supplement and intralesional vitamin D injections on hypertrophic scars and keloids. Group II: patients with sufficient vitamin D received only intralesional vitamin D injections.

Vitamin D deficiency did not affect scar formation or severity (total Vancouver scar scale before assessment) with a p value > 0.05. All instances showed a substantial drop in vascularity, pliability, and total Vancouver scale score (p value < 0.05) following intervention, but no change in scar pigmentation or height. Scar assessment following intervention did not significantly differ between research groups (p > 0.05).

Injection of vitamin on hypertrophic scars and keloids enhances vascularity and pliability in patients with sufficient serum vitamin D levels and those with deficient or insufficient serum vitamin D levels after improving them by systemic injection of vitamin D without any effect on height and pigmentation of scars.

NCT06301178.

Background and Objectives: Pediatric patients can acquire scars from both accidental injury and surgical procedures. While scars cannot be avoided if a full-thickness injury occurs, scar visibility may be minimized through a variety of approaches. In this narrative review, we evaluate the current evidence and propose an algorithm for scar management in pediatric patients. Materials and Methods: A review of the literature was performed for scar management techniques for pediatric patients. Management modalities based on the type of scar and dosing, treatment regimen, and safety profiles are described in this article and used to create a scar management algorithm. Results: The initial step to scar management in the pediatric population involves ensuring minimal wound tension, which can be achieved through making the incision along relaxed skin tension lines, and early, minimal tension wound closure. Subsequent treatments to optimize scar care should begin 2-3 weeks following wound closure and involve the application of silicone gel or sheets and scar massaging. When topical products are insufficient, laser therapy can be utilized for the management of immature erythematous or thick scars. When mature, pathological scars form such as atrophic scars, hyperpigmentation, hypertrophic scars, or keloids, a combination of modalities is recommended. These modalities vary by scar type and include retinoids and dermabrasion for atrophic scars; retinoids, hydroquinone, and laser therapy for hyperpigmentation; and pressure therapy, corticosteroids, and laser therapy for hypertrophic scars and keloids. When mature, pathological scars persist following 12 months of non-invasive therapies, surgical excision should be considered. Conclusions: Several treatment options are available to manage scars in the pediatric population depending on scar type.

Hypertrophic scar (HS) is a disease with excessive skin fibrosis and collagen disorder, which is generally caused by abnormal wound repair process after burn and trauma. Although intralesional injection of 5-fluorouracil (5-Fu) has been used in clinical treatment of HS, the patients' compliance of injection treatment is poor. In this study, a double-layer dissolution microneedle (MN) containing asiaticoside (AS) and 5-Fu was designed for the treatment of HS. Biological macromolecules materials affected the formability, drug release, and hardness of MNs. Therefore, several types of biomacromolecules, including hyaluronic acid (HA), chitosan, and sodium alginate, which could be used to prepare MNs, underwent prescription optimization experiments and the optimized MN prescriptions were obtained. In vitro characterization showed that the MN was sufficient to deliver drugs through the skin. Animal in vivo experiments showed that AS and 5-Fu can synergistically treat HS, significantly reduce the abnormal proliferation of fibroblasts and collagen fiber deposition, and down-regulated collagen I (Col I) and transforming growth factor-β1 (TGF-β1) expression. In conclusion, the micro-needle designed in this study has great prospects in the treatment of HS.

Dermal white adipose tissue (dWAT), distinguished by its origin from cells within the dermis and independence from subcutaneous fat tissue, has garnered significant attention for its non-metabolic functions. Characterized by strong communication with other components of the skin, dWAT mediates the proliferation and recruitment of various cell types by releasing adipogenic and inflammatory factors. Here, we focus on the modulatory role of dWAT at different stages during wound healing, highlighting its ability to mediate the adipocyte-to-myofibroblast transition which plays a pivotal role in the physiology and pathology processes of skin fibrosis, scarring, and aging. This review highlights the regulatory potential of dWAT in modulating wound healing processes and presents it as a target for developing therapeutic strategies aimed at reducing scarring and enhancing regenerative outcomes in skin-related disorders.

Hypertrophic scars result from abnormal healing following skin injuries.

To delve deeper into the causal association between inflammatory factors and hypertrophic scars.

This study utilized genetic data from the FINN cohort and pertinent literature to scrutinize the nexus between a spectrum of inflammatory factors-encompassing IL-1β, interleukin 1 receptor-like 1, MCP1, RANTES/CCL5, TNFα, IL-8, IL-18, and CTACK/CCL27-and the risk of hypertrophic scarring. Our analytical strategy was based on the inverse variance weighted (IVW) approach, further bolstered by MR-Egger, weighted median, and weighted mode methods to ensure a comprehensive assessment. The reliability of our findings was rigorously appraised through Cochran's Q test, MR-Egger regression, MR-PRESSO, and leave-one-out analysis.

The genetic prediction results revealed a significant association between CTACK and hypertrophic scars (OR 1.21, 95% CI 1.05-1.4, p = 0.01) using the IVW method, although it was not corroborated by other MR analysis methods. The remaining inflammatory factors did not exhibit significant correlations with the risk of hypertrophic scar formation (all p > 0.05). The absence of significant heterogeneity among the IVs was indicated by Cochran's Q test. MR-Egger and MR-PRESSO analyses collectively suggested no substantial horizontal pleiotropy influencing the results, except for the relationship between RANTES and hypertrophic scars. Upon exclusion of an outlier, the causal relationship between RANTES and hypertrophic scars was found to be non-significant.

Our MR analysis supports a causal association between CTACK and hypertrophic scars, enhancing our understanding of scar formation and suggesting potential targeted therapeutic strategies for treatment.

Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions postcutaneous injury, and even though KD remains neoplastically benign, keloid lesions behave locally aggressive, invasive and expansive. To date, there is limited understanding and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim in this study was to identify putative causative candidates in KD by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analysis to demonstrate that NF-kB-p65 (RELA) from the cytosolic fraction and CAPN2 from the whole-cell lysate were statistically significantly upregulated in KD and associated with alterations in relevant key signaling pathways, including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, subcellular fractionation and metaproteogenomic analyses have identified, to our knowledge, 2 previously unreported biomarkers of significant relevance to keloid diagnostics and therapeutics.

Hypertrophic scar (HS) is acknowledged as a pathological fibro-proliferative disease of the dermis, resulting from excessive connective tissue growth. HS significantly impacts patient quality of life due to both social and functional issues. Despite various treatments, therapeutic effectiveness remains limited, necessitating further exploration of underlying factors and mechanisms.

The current study was designed to determine the causal relationship between skin microbiota and HS employing a bidirectional Mendelian randomization (MR) approach.

We utilized genome-wide association study (GWAS) data from the PopGen cohort and the FinnGen database. Independent single nucleotide polymorphisms (SNPs) linked to the skin microbiota were identified as instrumental variables (IVs) chosen for the two-sample MR analysis. Key analytical approaches included inverse variance weighting (IVW), MR-Egger, simple median, simple mode, and weighted mode, with MR-Egger intercept test and Cochrane's Q test used to detect potential horizontal pleiotropy and heterogeneity.

The two-sample MR analysis identified significant causal relationships between specific skin microbiota features and HS. Notably, Enhydrobacter, Micrococcus, and Acinetobacter on moist skin exhibited protective effects against HS, whereas Finegoldia and Lactobacillales on dry skin were linked to an increased risk of HS. Sensitivity analyses verified the strength of these results, revealing no notable horizontal pleiotropy or heterogeneity.

Our research reveals a unidirectional causal relationship between certain skin microbiota and HS, suggesting that modulation of skin microbiota could be a novel therapeutic approach for HS management. These results emphasize the significance of considering skin microbiota in the pathogenesis and treatment of HS.

This randomized controlled trial aimed to investigate the potential benefits of local application of triamcinolone acetonide combined with topical recombinant bovine basic fibroblast growth factor in promoting wound healing and reducing scar formation after circumcision using a stapler device.

A total of 192 patients with phimosis or redundant prepuce were randomly assigned to either the observation group (n = 96) or the control group (n = 96). Both groups underwent circumcision using a stapler device. Postoperatively, the observation group received wet dressings of 2 mg/mL triamcinolone acetonide solution combined with topical recombinant bovine basic fibroblast growth factor until complete wound healing. The control group received saline wet dressings and standard postoperative wound care. Outcome measures included: postoperative edema, time to resolution of swelling at the incision edges, wound exudate, healing time, staple removal time and rate, scar formation, and patient satisfaction with penile cosmesis.

The observation group demonstrated significantly faster healing times and lower incidence of edema from the seventh postoperative day compared to the control group (P < .05). Furthermore, the observation group exhibited superior outcomes in terms of complete staple removal time, staple detachment rate, scar hypertrophy, and cosmetic scores using the modified Stony Brook Scar Evaluation Scale (P < .05). Patient satisfaction with penile cosmesis was also significantly higher in the observation group (P < .05).

This study underscores the principle of "prevention over treatment" in scar management following stapler circumcision. The findings suggest that the combined use of triamcinolone acetonide and recombinant bovine basic fibroblast growth factor may be beneficial in reducing postoperative edema, improving scar formation, and enhancing patient satisfaction. However, further research is warranted to validate these findings, establish optimal treatment protocols, and ultimately assess the long-term efficacy and safety of this combined therapy.

The synergistic effect of corticosteroids and 5-fluorouracil (5-FU) for the treatment of pathological scarring is widely documented. While topical administration can be a painless, convenient way to convey the two active ingredients, physical enhancement techniques such as microneedling are required to deepen their skin penetration and achieve the therapeutic effect. A novel approach to keloid and scar treatment is given by microincision, i.e., micrometric-sized columnar perforations which allow the drugs to diffuse into the skin and promote tissue proliferation in a more physiological structure. Combining the delivery of triamcinolone acetonide (TAC) and 5-FU with microincision is an innovative approach that could improve the speed and efficacy of regenerative treatments. This study evaluated the effectiveness of the skin treatment with a device combining microincisions and photobiomodulation, in the skin permeation of a combination of TAC and 5-FU. Increasing treatment times (4, 6, and 8 min) led to higher drug penetration compared to intact skin, with a more noticeable effect for 5-FU compared to TAC. Specifically, all treatment durations were significantly more effective (p < 0.05) than the control for 5-FU, while TAC showed less variation between treatments. Moreover, it was shown that in-vitro, the permeation improvement given by the red-light treatment was mainly due to the mechanical massage, which pushed the actives into the microchannels created by the treatment. The application of prolonged skin microincision times ensured much higher skin permeation of both TAC and 5-FU compared to microneedling on healthy excised skin.

Keloids are abnormal scars formed due to fibroblast dysfunction and excessively deposited extracellular matrix (ECM). Despite the unclear process leading to the occurrence of keloids, several studies have demonstrated that histamine and its H1 receptor can effectively regulate fibroblast functions, contributing to keloid formation. Chlorpheniramine maleate (CPM) as a first-generation H1 antihistamine has been widely applied in symptomatic treatment of allergic conditions but its effects on keloids are unknown. This study holds the objective of exploring its effect on keloids. Cell Counting Kit-8 (CCK-8), apoptosis, cell cycle and migration assays were conducted to determine the effects of CPM on human keloid fibroblasts (KFs), with its therapeutic effect evaluated by constructing a keloid model in nude mice. RNA sequencing analysis, ELISA, western blotting and immunohistochemistry assisted in examining the anti-keloid mechanism of CPM. It was observed that CPM inhibited the proliferation and migration of KFs, promoted apoptosis of KFs, and blocked the G0/G1 phase of KFs. Moreover, local intralesional injection of CPM into nude mice keloid model significantly reduced keloid scars. According to RNA sequencing analysis, the gene expression of IL-6 and JAK-STAT signaling pathway were both negatively related in CPM group versus the control group. According to the in vivo and vitro experiment results, the anti-keloid activity of CPM was attributed to its inhibitory effect on the IL-6/JAK1/STAT3 signal pathway. In summary, CPM holds great potential for localized treatment of keloids.

Background: Postoperative scarring can significantly impact physical function, aesthetic outcomes, and overall quality of life. Effective scar management is crucial to mitigate these effects. This study aimed to compare the efficacy of silicone sheets (SS) and hyperbaric oxygen therapy (HBOT) in minimizing postoperative scar formation and improving wound healing outcomes. Methods: A total of 40 patients with clean, non-infected linear postoperative wounds were enrolled in a 12-week prospective observational study. Participants were randomly assigned to either the HBOT or SS group. The HBOT group underwent seven sessions of HBOT starting 4 weeks postoperatively, while the SS group applied silicone sheets to the wound from 4 to 12 weeks postoperatively. Scar outcomes were evaluated at 4, 8, and 12 weeks using the Patient and Observer Scar Assessment Scale (POSAS), which measures various parameters, including vascularity, pigmentation, thickness, relief, pliability, surface area and overall opinion. Results: After applying exclusion criteria, 33 patients completed the study, with 18 in the HBOT group and 15 in the SS group. Both interventions significantly improved scar parameters such as vascularity, thickness, relief, pliability, and overall opinion over 12 weeks. SS was particularly effective in reducing pigmentation, while HBOT achieved greater reductions in scar surface area. By the study's conclusion, SS demonstrated superior outcomes in vascularity, pigmentation, scar thickness, relief, pliability, and overall appearance, whereas HBOT excelled in reducing surface area. Conclusion: Both HBOT and SS are effective scar management options, each with unique benefits. Selecting the appropriate treatment based on patient-specific needs and wound characteristics is essential to achieve optimal outcomes and enhance patient satisfaction.

Keloid, scar caused by atypical wound repair, represents a significant difficulty for specialists in plastic surgery and dermatology. Adipose-derived mesenchymal stem cells (ADSCs) can regulate fibrotic phenotypes of keloid fibroblasts (KFs) in a paracrine fashion, but whether small extracellular vesicles (SEVs) are the key functional carrier in ADSC paracrine regulation of KFs remains unknown. This study aims to explore whether the regulatory effects of conditioned medium (CM) obtained from ADSCs on KFs can be impaired by decreased SEV content in the ADSC-CM.

Clinical specimens were utilized to extract keloid fibroblasts (KFs), normal fibroblasts (NFs), and adipose-derived stem cells (ADSCs). Fibroblasts were cultured with CM obtained from ADSCs untreated or treated with the sphingomyelinase inhibitor GW4869. The features of SEVs derived from ADSC-CM were characterized, and fibroblast proliferation, migration, apoptosis, and expression of ECM proteins were analyzed.

The sphingomyelinase inhibitor GW4869 successfully reduced the SEV content in ADSC-CM, and both control ADSC-CM and ADSC-CM with reduced SEV content significantly inhibited KF proliferation, migration, and α-SMA synthesis but not KF apoptosis, whereas only NF proliferation was inhibited by ADSC-CM. The reduced SEV content only affected the inhibition of KF proliferation induced by ADSC-CM.

ADSC-CM inhibits various fibrotic phenotypes of KFs, but decreasing the SEV content in ADSC-CM did not significantly alter the antifibrotic effects of ADSC-CM. Thus, SEVs may not be the key mediator of ADSCs paracrine regulation of KFs.

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Hypertrophic scar (HS) is a common fibroproliferative disorders with no fully effective treatments. The conversion of fibroblasts to myofibroblasts is known to play a critical role in HS formation, making it essential to identify molecules that promote myofibroblast dedifferentiation and to elucidate their underlying mechanisms. In this study, we used comparative transcriptomics and single-cell sequencing to identify key molecules and pathways that mediate fibrosis and myofibroblast transdifferentiation. Epidermal stem cell-derived extracellular vesicles (EpiSC-EVs) were isolated via ultracentrifugation and filtration, followed by miRNA sequencing to identify miRNAs targeting key molecules. After in vitro and in vivo treatment with EpiSC-EVs, we assessed antifibrotic effects through scratch assays, collagen contraction assays, Western blotting, and immunofluorescence. Transcriptomic sequencing and rescue experiments were used to investigate the molecular mechanism by which miR-203a-3p in EpiSC-EVs induces myofibroblast dedifferentiation. Our results indicate that PIK3CA is overexpressed in HS tissues and positively correlates with fibrosis. EpiSC-EVs were absorbed by scar-derived fibroblasts, promoting dedifferentiation from myofibroblasts to quiescent fibroblasts. Mechanistically, miR-203a-3p in EpiSC-EVs plays an essential role in inhibiting PIK3CA expression and PI3K/AKT/mTOR pathway hyperactivation, thereby reducing scar formation. In vivo studies confirmed that EpiSC-EVs attenuate excessive scarring through the miR-203a-3p/PIK3CA axis, suggesting EpiSC-EVs as a promising therapeutic approach for HS.

Cutaneous hypertrophic scar is a fibro-proliferative hard-curing disease. Recent studies have proved that antagonists of angiotensin II type 1 receptor (AT1R) and agonists of type 2 receptor (AT2R) were able to relieve hypertrophic scar. Therefore, establishing new methods to pursue dual-target lead compounds from Chinese herbs is in much demand for treating scar.

To this end, we immobilized AT1R or AT2R onto the surface of silica gel from cell lysates through a specific covalent bond by bioorthogonal chemistry. The columns containing immobilized AT1R or AT2R were jointly utilized to pursue potential bioactive compounds simultaneously binding to AT1R and AT2R from the extract of Rhei Radix et Rhizoma. Their functions on AT1R and AT2R expressions were investigated by in vitro and in vivo experiments.

Aloe-emodin and emodin were identified as the potential bioactive compounds binding to both of the two receptors, thereby improving the appearance and pathomorphology of hypertrophic scar. They blocked the AT1R pathway to down-regulate the expression of transforming growth factor-β1 (TGF-β1) and stimulate matrix metalloproteinase-1 (MMP-1) expression. As such, the expression of collagen I/III reduced. Conversely, the bindings of the two compounds to AT2R reduced the production of nuclear factor-кB1 (NF-кB1), whereby the generation of interleukin-6 (IL-6) was blocked.

We reasoned that aloe-emodin and emodin had the potential to become dual-target candidates against hypertrophic scar through the regulation of AT1R and AT2R signaling pathways. It showed considerable potential to become a universal strategy for pursuing multi-target bioactive compounds from Chinese herbs by the utilization of diverse immobilized receptors in a desired order.

This study investigated the knowledge, attitude, and practice (KAP) of aesthetic medicine practitioners concerning laser and/or light therapy for hypertrophic scars. Conducted at Hebei Medical University Third Hospital from December 25, 2023, to January 7, 2024, the cross-sectional study utilized a self-administered questionnaire to gather socio-demographic data and KAP scores. A total of 424 valid questionnaires were collected, with 220 (52.26%) female participants. The mean scores were 27.24 ± 4.28 for knowledge (range 8-40), 34.14 ± 3.49 for attitude (range 9-45), and 26.22 ± 3.46 for practice (range 6-30). Significant positive correlations were observed between knowledge and attitude (r = 0.471, P < 0.001), knowledge and practice (r = 0.593, P < 0.001), and attitude and practice (r = 0.640, P < 0.001). Multivariate logistic regression revealed that both knowledge (OR = 1.260, P < 0.001) and attitude scores (OR = 1.547, P < 0.001), along with the intermediate professional title (OR = 0.233, P = 0.042), were significantly associated with proactive practice. The findings indicate a need for targeted educational initiatives to enhance practitioners' knowledge in this area.

Bacterial colonisation in hypertrophic scars (HSs) has been reported, yet the precise mechanism of their contribution to scar formation remains elusive. To address this, we examined HS and normal skin (NS) tissues through Gram staining and immunofluorescence. We co-cultured fibroblasts with heat-inactivated Staphylococcus aureus (S. aureus) and evaluated their levels of apoptosis and proliferation by flow cytometry and Cell Counting Kit-8 assay, respectively. Additionally, we performed proteomic analysis and western blotting to identify upregulated proteins. To assess autophagy levels, we examined light chain 3 (LC3) expression through western blotting and immunofluorescence, and transmission electron microscopy (TEM) was performed to detect autophagy-associated vesicles. Our results demonstrated a notable increase in bacterial load, primarily S. aureus, in HS tissues. Furthermore, S. aureus promoted fibroblast proliferation and enhanced the expression of profibrotic markers such as transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), collagen I, collagen III and α smooth muscle actin (α-SMA). Proteomic analysis highlighted heat shock factor-binding protein 1 (HSBP1) as a key upregulated protein mediating the profibrotic effects induced by S. aureus. Knockdown of HSBP1 reversed these effects. Intriguingly, HSBP1 also upregulated LC3 and Beclin-1 expression and increased the number of autophagosomes in fibroblasts. Finally, when fibroblasts stimulated by S. aureus were treated with HSBP1 siRNA, autophagy levels decreased significantly. Collectively, our findings suggest that S. aureus, via HSBP1, stimulates fibroblast proliferation and promotes their transition into myofibroblasts, triggering autophagy and fibrosis. These results underscore the potential of HSBP1 as a therapeutic target for the management of HSs.

Keloids, characterized by protruding scars that extend beyond the original skin damage site, cause significant emotional stress and reduced quality of life. Their exact pathogenesis remains unclear, with various hypotheses including growth factor imbalances and extracellular matrix changes. No single treatment is universally accepted, but multiple modalities like triamcinolone acetonide injection (TAC), laser therapies, and surgery are commonly used.

This retrospective study involved East Asian patients who underwent keloid scar excision between March 2019 and June 2022. Patients were divided into two groups: one receiving only TAC injections and the other a combination of TAC and Nd:YAG laser therapy. The efficacy of treatments was evaluated using the modified Vancouver Scar Scale (mVSS) and the Patient and Observer Scar Assessment Scale (POSAS), with follow-ups at six and twelve months after operation.

The study involved 111 patients. Both treatment groups showed significant improvements in mVSS and POSAS scores, but the combination therapy group demonstrated a statistically significant improvement in POSAS scores and lower recurrence rates at 12 months compared to the TAC-only group. However, there was no significant difference in patient satisfaction between the groups.

Dual therapy involving TAC injection and Nd:YAG laser treatment was more effective than TAC injection alone for managing keloid scars after surgery. This combination therapy showed better outcomes in preventing keloid recurrence and improving scar status at 12 months after operation, along with significant improvements in patient-reported outcomes.

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Hypertrophic scar (HS) is a fibroproliferative disorder resulting from abnormal healing of skin tissue after injury. Although various therapies are currently employed in clinical to treat HSs, there is no widely accepted standard therapy. Micro-plasma radiofrequency (MPR) and autologous chyle fat grafting are emerging treatments for this condition, and they have demonstrated promising therapeutic outcomes in clinical applications. The aim of this study is to investigate the effectiveness and safety of combining MPR with autologous chyle fat grafting for the treatment of HSs.

We performed a retrospective study on patients diagnosed with HS in a single center between January 2020 and December 2023. According to the treatments, patients were divided into three groups, with 6 months follow-up. The single therapy group received MPR alone for two times. The combined therapy Group 1 first received the MPR treatment followed by the combined treatment. The combined therapy Group 2 first received the combined treatment and then received the MPR treatment. The effectiveness of treatment was evaluated using the Vancouver Scar Scale (VSS) and the Patient Scar Assessment Scale (PSAS). The Visual Analog Scale (VAS) was used to assess the patients' pain on the day of treatment and 1 day after treatment. Adverse events and complications were recorded to assess the safety of treatment.

A total of 73 patients diagnosed with HS were enrolled in this study, including 35 patients in the single therapy group, 18 patients in the combined therapy Group 1, and 20 patients in the combined therapy Group 2. After the treatments were completed, all three groups exhibited significant effectiveness. The two combined therapy groups scored lower after treatments in the VSS, which includes height, vascularity, pliability, and total scores, as well as in the PSAS, which includes color, stiffness, thickness, and total scores, compared to the single therapy group, with a statistically significant difference. Regarding pain response to treatment, there was no statistical difference in VAS among the three groups. No statistical difference in the overall incidence of adverse events was observed among the three groups, and no severe complications were recorded.

This study revealed the combination of MPR and autologous chyle fat grafting showed superior effectiveness compared to MPR alone in treating HSs, without any observed increase in overall adverse event frequency. For patients diagnosed with HS, this combination therapy stands as a promising and effective clinical intervention.

Observational studies have linked pathological scars to hypertension; however, the causality remains ambiguous. In this study, we aimed to explore this issue using Mendelian randomization (MR). We obtained genome-wide association study data for hypertrophic scar and hypertension from the IEU Open genome-wide association study project [hypertension (containing 9851,867 SNPs, observation group of 124,227, and control group of 337,653), hypertrophic scars (containing 16,380,443 SNPs with a sample mass of 207,482), and keloids (containing 24,197,210 SNPs and sample volume of 481,912)]. The inverse variance weighted method and MR-Egger test were used, followed by a sensitivity analysis. With hypertension as the exposure and hypertrophic scar as the outcome, we obtained the IVW analysis results (OR = 0.264, 95% CI = 0.098-0.709, P = .008) and the MR-Egger test results (OR = 0.036, 95% CI = 0.002-0.544, P = .017); for keloid as the outcome, the results of IVW analysis showed OR = 0.592, 95% CI = 0.293-1.195, P = .143. Contrary to the findings of observational studies, our results revealed hypertension as a protective factor against hypertrophic scarring, and was unrelated to keloids.

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.

Wound healing is an ongoing concern for the medical community. The limitations of traditional dressings are being addressed by materials and manufacturing technology. Microneedles (MNs) are a novel type of drug delivery system that has been widely used in cancer therapy, dermatological treatment, and insulin and vaccine delivery. MNs locally penetrate necrotic tissue, eschar, biofilm and epidermis into deep tissues, avoiding the possibility of drug dilution and degradation and greatly improving administration efficiency with less pain. MNs represent a new direction for wound treatment and transdermal delivery. In this study, we summarise the skin wound healing process and the mechanical stimulation of MNs in the context of the wound healing process. We also introduce the structural design and manufacture of MNs. Subsequently, MNs are categorised according to the loaded drugs, where the design of the MNs according to the traumatic biological/biochemical microenvironment (pH, glucose, and bacteria) and the physical microenvironment (temperature, light, and ultrasound) is emphasised. Finally, the advantages of MNs are compared with traditional drug delivery systems and their prospects are discussed.

Keloid scarring is a fibroproliferative disease of the skin, which can significantly impact one's quality of life through cosmetic concerns, physical discomfort (itchy; painful), restricted movement, and psychological distress. Owing to the poorly understood pathogenesis of keloids and their high recurrence rate, the efficacy of keloid treatment remains unsatisfactory, particularly in patients susceptible to multiple keloids. We conducted fecal metagenomic analyzes and both untargeted and targeted plasma metabolomics in patients with multiple keloids (MK, n = 56) and controls with normal scars (NS, n = 60); tissue-untargeted metabolomics (MK, n = 35; NS, n = 32), tissue-targeted metabolomics (MK, n = 41; NS, n = 36), and single-cell sequencing analyzes (GSE163973). Differences in the gut microbiota composition, plasma metabolites, and tissue metabolites were observed between the MK and NS groups; the core gut microbiota, Oxalobacter formigenes, Bacteroides plebeius, and Parabacteroides distasonis, were identified via the gut microbiome co-occurrence network. Single-cell data helped clarify the specific cells affected by plasma metabolites. An area under the curve analysis using a random forest model based on fecal metagenomics, plasma metabolomics, and tissue metabolomics revealed that gut bacteria, plasma, and tissue metabolites were effective in distinguishing between MK and NS groups. Decreased Bacteroides plebeius could lower uracil levels, altering systemic lipid metabolism, which may change the metabolic phenotype of secretory reticular fibroblasts in wounds, potentially leading to MK. These findings may open new avenues for understanding the multifactorial nature of keloid formation from the gut-skin axis and highlight the potential for novel therapeutic strategies targeting keloid lesions and the underlying systemic imbalances affected by the gut microbiome.

Wound regeneration with integral function and cutaneous appendages remains challenging in wound dressing applications. Cellulose nanofibers (CNF) exhibit remarkable characteristics in wound dressing applications; however, their utility in the wound healing process is limited by insufficient scar inhibition and regenerative healing. Herein, inspired by fibroblast heterogeneity mediating wound healing and skin regeneration, we developed a CNF scaffold designed to block Dipeptidyl Peptidase 4 positive (DPP4+) fibroblasts for regenerative healing. CNF encapsulated sitagliptin (SITA) and zinc sulfide nanoparticles (NZnS), namely CNF@SITA@NZnS, to fabricate a novel biomaterial for scar reduction and regenerative healing. The scaffold promoted scarless healing and hair follicle regeneration in rats. In vivo experiments, the wounds in the scaffold showed less skin fibrosis, a better collagen ratio and more new hair follicles. In vitro experiments showed that the scaffold material promoted scarless healing, possibly by inhibiting the secretion of extracellular matrix and fibroblast-to-myofibroblast conversion. The promotion of hair follicle regeneration by the scaffold material may be due to promotion of the migration and proliferation of human hair follicle papilla cells. RNA sequencing is performed to explore the underlying mechanisms, which can activate ECM-receptor interaction pathway in favor of the wound healing process. The inhibiting effect of CNF@SITA@NZnS scaffold on DPP4+ fibroblasts can be a potential target to reduce scarring and promote skin regeneration.

Cortex Moutan is the root bark of the buttercup plant Paeonia suffruticosa Andr, of Ranunculaceae family. It has been utilized in Chinese medicine for thousands of years to treat a multitude of diseases, and traditional Chinese documents allege that it has heat-clearing, antipyretic, anti-inflammatory and detoxicating properties. Paeonol is a bioactive substance extracted from Cortex Moutan, which is considered to be one of its most effective metabolites. Recent studies have illustrated that paeonol treatment can alleviate skin damage, relieve the inflammatory response in patients with numerous dermatological conditions, and inhibit anomalous proliferation of skin tissue. Accordingly, paeonol may serve as a potential therapeutic agent for a variety of skin conditions. This review summarizes the physicochemical properties and pharmacokinetics (PK) characteristics of paeonol, and mechanisms of operation in diverse skin diseases, including dermatitis, psoriasis, pruritus, photoaging, hyperpigmentation, and hyperplasticscar. Additionally, much of the evidence is based on animal experiments. Furthermore, it explores the prospects of enhancing paeonol's efficacy through extraction, synthesis, and formulation innovations, as well as strategies to overcome its limitations in dermatological therapy. This review aims to provide a more reliable theoretical basis for the clinical application of paeonol.

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.

This protocol introduces a streamlined and efficient method for isolating human fibroblast from skin primary cell culture with a specific focus on its application to keloid, hypertrophic scar, and normal skin biopsies. Additionally, the absence of suitable animal models for keloid and hypertrophic scar has led preclinical research to rely on in vitro studies using primary cell cultures. This approach addresses the challenges of existing protocols in terms of time, cost, equipment, and technical expertise required. The method involves derivation, culture, and characterization analysis including cell proliferation, migration, and fibroblastic marker (Vimentin, CD90, CD73, and CD105) expression. Our study yielded high amounts of fibroblast from tested skin explants while maintaining their in vivo-like characteristics and behaviour. Immunostaining assay confirmed that the cultivated fibroblast was positively expressed Vimentin. Flowcytometry results showed high expression of CD90 and CD73 while relatively showing lower expression of CD105. Fibroblast derived from keloid tissue showed the highest rate of proliferation and migration ability compared to the other samples. These findings suggest an efficient and reproducible technique to cultivate high qualified fibroblast from human skin in normal or pathological condition, particularly for keloid and hypertrophic scar. The application of this protocol provides a foundation for further studies to investigate the progression and potential intervention of aberrant fibrotic dermatological disorder, in vitro.

Background/Objectives: Dermal fibroblasts (DFs) are key participants in skin hypertrophic scarring, and their properties are being studied to identify the molecular and cellular mechanisms underlying the pathogenesis of skin scarring. Methods: In the present work, we performed a comparative analysis of DFs isolated from normal skin (normal dermal fibroblasts, NDFs), and hypertrophic scar skin (hypertrophic scar fibroblasts, HTSFs). The fibroblasts were karyotyped and phenotyped, and experiments on growth rate, wound healing, and single-cell motility were conducted. Results: Comparative analysis revealed a minor karyotype difference between cells. However, HTSFs are characterized by higher proliferation level and motility compared to NDFs. These significant differences may be associated with quantitative and qualitative differences in the cell secretome. A proteomic comparison of NDF and HTSF found that differences were associated with metabolic proteins reflecting physiological differences between the two cells lines. Numerous unique proteins were found only in the vesicular phase of vHTSFs. Some proteins involved in cell proliferation (protein-glutamine gamma-glutamyltransferase K) and cell motility (catenin delta-1), which regulate gene transcription and the activity of Rho family GTPases and downstream cytoskeletal dynamics, were identified. A number of proteins which potentially play a role in fibrosis and inflammation (mucin-5B, CD97, adhesion G protein-coupled receptor E2, antileukoproteinase, protein S100-A8 and S100-A9, protein caspase recruitment domain-containing protein 14) were detected in vHTSFs. Conclusions: A comparative analysis of primary cell cultures revealed their various properties, especially in the cell secretome. These proteins may be considered promising target molecules for developing treatment or prevention strategies for pathological skin scarring.

Laser therapy has emerged as a promising treatment modality for improving the appearance and symptoms associated with hypertrophic and keloid scars. In this network meta-analysis, we aimed to evaluate the efficacy of different laser types in treating hypertrophic and keloid scars.

A comprehensive search of four databases was conducted to identify relevant studies published up until July 2023. Data were extracted from eligible studies and pooled as mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous data in a network meta-analysis (NMA) model, using R software.

A total of 18 studies, comprising 550 patients, were included in the analysis. Pooling our data showed that fractional carbon dioxide (FCO2) plus 5-fluorouracil (5-FU) was superior to control in terms of Vancouver Scar Scale (VSS), pliability score, and thickness; [MD = - 5.97; 95% CI (- 7.30; - 4.65)], [MD = - 2.68; 95% CI (- 4.03; - 1.33)], [MD = - 2.22; 95% CI (- 3.13; - 1.31)], respectively. However, insignificant difference was observed among FCO2 plus 5-FU compared to control group in terms of erythema, vascularity, redness and perfusion, and pigmentation [MD = - 0.71; 95% CI (- 2.72; 1.30)], [MD = - 0.44; 95% CI (- 1.26; 0.38)], respectively.

Our NMA found that the FCO2 plus 5-FU was the most effective intervention in decreasing the VSS and thickness, while FCO2 plus CO2 was the most effective intervention in decreasing the pliability score. Further research is needed to determine the optimal laser parameters and long-term efficacy of laser therapy in hypertrophic and keloid scars.

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 .