Search

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: 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., Aims: This study aimed to assess topical bleomycin's efficacy and safety in treating hypertrophic scars and keloids., Methods: 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%)., Results: 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., Conclusions: 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., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Hypertrophic scar (HS) formation is a cutaneous fibroproliferative disease that occurs after skin injuries and results in severe functional and esthetic disability. To date, few drugs have shown satisfactory outcomes for the treatment of HS formation. Transforming growth factor-beta (TGF-β)/Notch interaction via small mothers against decapentaplegic 3 (Smad3) could facilitate HS formation; therefore, targeting TGF-β/ Notch interaction via Smad3 is a potential therapeutic strategy to attenuate HS formation. In addition, optic atrophy 1 (OPA1)-mediated mitochondrial fusion contributes to fibroblast proliferation, and TGF-β/Smad3 axis and the Notch1 pathway facilitate OPA1-mediated mitochondrial fusion. Thus, the aim of this study was to investigate whether drugs targeting TGF-β/Notch interaction via Smad3 suppressed fibroblast proliferation to attenuate HS formation through OPA1-mediated mitochondrial fusion. We found that the TGF-β pathway, Notch pathway, and TGF-β/Notch interaction via Smad3 were inhibited by pirfenidone, the gamma- secretase inhibitor DAPT, and SIS3 in human keloid fibroblasts (HKF) and an HS rat model, respectively. Protein interaction was detected by co-immunoprecipitation, and mitochondrial morphology was determined by electron microscopy. Our results indicated that pirfenidone, DAPT, and SIS3 suppressed the proliferation of HKFs and attenuated HS formation in the HS rat model by inhibiting TGF-β/Notch interaction via Smad3. Moreover, pirfenidone, DAPT, and SIS3 hindered OPA1-mediated mitochondrial fusion through inhibiting TGF-β/Notch interaction, thereby suppressing the proliferation of HS fibroblasts and HS formation. In summary, these findings investigating the effects of drugs targeting TGF-β/Notch interaction on HS formation might lead to novel drugs for the treatment of HS formation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension., Aims: To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension., Methods: Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual-plane micro-drop injections, triamcinolone acetonide (TAC) suspension, and CO 2 via fractional CO 2 laser. Interventions were implemented in all three groups once a month for three consecutive sessions. After the final treatment, scarring was evaluated at 1, 3, 6, 12, and 24 months using the Patient and Observer Scar Assessment Scale (POSAS)., Results: The 3-month POSAS score for each scar indicator in the treatment groups was significantly lower than that in the preoperative groups (p < 0.001). The scar score in the TAC group decreased at 3 months and increased thereafter. For other groups, the scar score continually decreased at all time points according to the Patient Scar Assessment Scale. Based on the Observer Scar Assessment Scale, the scar score continuously decreased at all time points in the BTA group; in the TAC group, it decreased at 1 month and increased thereafter; and in the CO 2 group, the scar score decreased at 3 months and subsequently stabilized., Conclusions: All three treatment methods were effective. However, the BTA group experienced a reduced risk of scar recurrence and maintained long-term treatment effects., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Hypertrophic scarring is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation. Existing drugs have not achieved satisfactory therapeutic effects., Objectives: To explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for their treatment., Methods: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model., Results: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, the transforming growth factor (TGF)-β signalling pathway and other biologic pathways. Integrin β1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and profibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA can also inhibit mouse scar hyperplasia., Conclusions: ITGB1 and TGF-β signalling pathways are important for hypertrophic scar formation. Crizotinib could be a potential treatment drug for hypertrophic scars., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Boswellic acids (BAs) showed promising effects in cancer treatment, immune response regulation, and anti-inflammatory therapy. We aimed to assess the roles of alpha-BA (α-BA) in treating acute wound healing., Methods: In vivo wound-healing models were established to evaluate the therapeutic effects of α-BA. Cell assays were conducted to assess the impact of α-BA on cellular biological functions. Western blot analysis was employed to validate the potential mechanisms of action of α-BA., Results: Animal models indicated that wound healing was notably accelerated in the α-BA group compared to the control group (P < 0.01). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) assay preliminarily suggested that α-BA may accelerate wound healing by inhibiting excessive inflammatory reactions and increasing the protein levels of growth factors. Cell function experiments demonstrated that α-BA suppressed the proliferation and migration ability of human hypertrophic scar fibroblasts (HSFBs), thereby favoring wound healing. Additionally, α-BA exerted a significant impact on cell cycle progression. Mechanistically, the protein levels of key genes in nuclear factor kappa beta (NF-κB) signaling pathway, including cyclin D1, p65, IκBα, and p-IκBα, were downregulated by α-BA., Conclusions: α-BA demonstrated the ability to counteract the abnormal proliferation of skin scar tissues, consequently expediting wound healing. These findings suggest its potential for development as a new agent for treating acute wound healing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly( ε -caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization ( 1 H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS-targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose-dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP-loaded non-bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes-associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies., (© 2023 Wiley‐VCH GmbH.)

Objective: This retrospective study aims to compare the efficacy rates in treating hypertrophic scars among four distinct groups of patients who either underwent fractional Erbium: yttrium-aluminum-garnet (Er:YAG) laser or microplasma radiofrequency technology as standalone treatments or in combination with compound betamethasone transdermal administration., Method: The study retrospectively examined 208 patients treated at our institution from April 2011 to December 2022 for hypertrophic scars, receiving no less than three treatments (with an interval of 8 weeks between each). The patients were categorized into four groups: the F group (treated with fractional Er:YAG laser), the F + B group (treated with fractional Er:YAG laser combined with compound betamethasone transdermal administration), the P group (treated with microplasma radiofrequency technology), and the P + B group (treated with microplasma radiofrequency technology combined with compound betamethasone transdermal administration). The therapeutic effects were evaluated based on the changes in the Vancouver Scar Scale (VSS) scores before and after treatment in these groups., Results: There was no statistically significant difference in the VSS scores among the four groups before treatment. After undergoing three sessions of the aforementioned four types of treatment, all groups showed a decrease in VSS scores, with average posttreatment VSS scores for the F group scored 5.15 ± 2.084, F + B group scored 3.7 ± 1.781, P group scored 4.41 ± 1.933, and P + B group scored 3.16 ± 1.775, respectively. With an increasing number of treatments, the total effective rate gradually increased in all four groups, and the combination treatment using compound betamethasone transdermal administration proved more effective than the standalone treatment., Conclusion: All four treatments yielded favorable outcomes, with the combined therapy involving compound betamethasone transdermal administration proving more effective than the standalone treatments, meriting further clinical attention., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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.

Introduction: Pathological scars, such as hypertrophic scars and keloids, are characterized by the proliferation of fibroblasts and the deposition of collagen that often cause pruritus, pain, and disfigurement. Due to their high incidence and deformity, pathological scars have resulted in severe physical and psychological trauma for patients. Intralesional injection of 5-fluorouracil (5-Fu) is a recommended option for treating pathological scars. However, the efficacy of 5-Fu injection was limited and unstable due to limited drug penetration and short retention time., Methods: Liposomes are promising carriers that have advantages, such as high biocompatibility, controlled release property, and enhanced clinical efficacy. Here, we constructed a transdermal 5-Fu-loaded liposome (5-Fu-Lip) to provide a more effective and safer modality to scar treatment., Results: Compared to 5-Fu, 5-Fu-Lip showed superior ability in inhibiting primary keloid fibroblasts proliferation, migration, and collagen deposition, and also significantly inhibited human umbilical vein endothelial cells (HUVECs) proliferation and microvessel construction. In vivo experiments demonstrated that 5-Fu-Lip can significantly reduce the severity of hypertrophic scars in a rabbit ear wounding model., Discussion: 5-Fu-Lip provides a promising strategy to improve drug efficacy, which has great potential in the treatment of pathological scars., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Li et al.)

Hypertrophic scar (HS) is a fibroproliferative skin disease characterized by abnormal wound healing and pathological excessive fibrosis of the skin. Currently, the molecular mechanism of the disease is still largely unknown, and there is no effective drug treatment. In this study, we explored the effect of Rynchopeterine on the formation of HS. HS fibroblasts (HSFs) were isolated from the HS tissues of patients recovering from severe burns. After treating HSFs with different concentrations of Rynchopeterine, CCK-8, EdU, and Annexin V-FITC/PI assays were used to detect the proliferation, apoptosis, and contractile ability of HSFs. RT-qPCR and Western blotting were performed to evaluate the effect of Rynchopeterine on the expression of miR-21 and hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). The dual-luciferase reporter gene was used to verify the targeting relationship between miR-21 and HIF1AN. Rynchopeterine reduced the expression of Col1a2, Col3a1, and α-SMA, inhibited proliferation and contraction of HSFs, and increased apoptosis in a dose-dependent manner. miR-21 was highly expressed in HS tissues and HSFs, and Rynchopeterine could inhibit miR-21 expression. Overexpression of miR-21 and knockdown of HIF1AN increased proliferation, activation, contraction, and collagen synthesis of HSFs, and inhibited their apoptosis. In vivo, Rynchopeterine could reduce the collagen content of the dermis and the positive ratio of PCNA and α-SMA. Rynchopeterine is a good therapeutic agent for HS, which up-regulates the expression of HIF1AN by inhibiting miR-21, thereby inhibiting the formation of HS., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hypertrophic scars (HS) are a common disfiguring condition in daily clinical encounters which brings a lot of anxieties and concerns to patients, but the treatment options of HS are limited. Black cloth ointment (BCO), as a cosmetic ointment applicable to facial scars, has shown promising therapeutic effects for facial scarring. However, the molecular mechanisms underlying its therapeutic effects remain unclear., Material and Methods: Network pharmacology was first applied to analyze the major active components of BCO and the related signaling pathways. Subsequently, rabbit ear scar model was successfully established to determine the pharmacological effects of BCO and its active component β-elemene on HS. Finally, the molecular mechanism of BCO and β-elemene was analyzed by Western blot., Results: Through the network pharmacology, it showed that β-elemene was the main active ingredient of BCO, and it could significantly improve the pathological structure of HS and reduce collagen deposition. BCO and β-elemene could increase the expression of ER stress-related markers and promote the increase of apoptotic proteins in the Western blot experiment and induce the apoptosis of myofibroblasts., Conclusions: Our findings indicate that the material basis for the scar-improving effects of the BCO is β-elemene, and cellular apoptosis is the key mechanism through which the BCO and β-elemene exert their effects., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Keloids and hypertrophic scars cause physical and psychosocial problems. A combination of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) may enhance the treatment of pathologic scars, although the evidence base is limited. The authors compared the efficacy and complication rates of combination intralesional TAC and 5-FU with those of monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars., Methods: Embase, MEDLINE, and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using the Cochrane risk of bias tool., Results: Of 277 articles screened, 13 studies were included, comprising 12 randomized control trials and one nonrandomized study. Six studies compared combination intralesional therapy versus monotherapy 5-FU, and nine studies compared combination intralesional therapy versus monotherapy TAC. The combined group demonstrated superior objective treatment efficacy compared with the monotherapy TAC group (OR, 3.45; 95% CI, 2.22 to 5.35; I 2 = 0%; P < 0.00001) and monotherapy 5-FU group (OR, 4.17; 95% CI, 2.21 to 7.87; I 2 = 0%; P < 0.0001). Telangiectasia was less frequent in combination therapy (OR, 0.24; 95% CI, 0.11 to 0.52; I 2 = 0%; P = 0.0003) compared with monotherapy TAC., Conclusions: Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared with monotherapy TAC or 5-FU. Patient-reported outcome measures should be incorporated in the design of future research to justify clinical recommendations., Clinical Relevance Statement: Combined TAC and 5-FU has demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU in the treatment of hypertrophic scars and keloids., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza - Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo . After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-β 1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.

Hypertrophic scars and keloids are the results of an exaggerated healing process and are often associated with significant patient morbidity. Fractional ablative lasers create microchannels in the skin and penetrate into the substance of the scar, inducing a normal healing response in zones of created damage. Focal delivery of scar-modulating agents into the scar through these microchannels-a process termed laser-assisted drug delivery (LADD)-is a promising and developing treatment modality. In this systematic review, we aim to critically examine the evidence of LADD in the treatment of hypertrophic scars and keloids. The evidence suggests that LADD improves outcomes in hypertrophic scars and keloids. LADD is a more effective treatment modality than the topical application of agents in hypertrophic scars and equally effective as the intralesional injection of agents in keloids. There were few reports of adverse events. Evidence supports the use of LADD as an adjunct to non-surgical measures or a treatment modality to be used before more invasive measures such as surgical excision. However, the quality of evidence supporting this conclusion is inconsistent and lacks power. Additional studies are required to optimize dosages, laser settings, and agent choices for the treatment of these lesions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Keloids (KD) and hypertrophic scars (HTS), which are quite raised and pigmented and have increased vascularization and cellularity, are formed due to the impaired healing process of cutaneous injuries in some individuals having family history and genetic factors. These scars decrease the quality of life (QOL) of patients greatly, due to the pain, itching, contracture, cosmetic problems, and so on, depending on the location of the scars. Treatment/prevention that will satisfy patients' QOL is still under development. In this article, we review pharmacotherapy for treating KD and HTS, including the prevention of postsurgical recurrence (especially KD). Pharmacotherapy involves monotherapy using a single drug and combination pharmacotherapy using multiple drugs, where drugs are administered orally, topically and/or through intralesional injection. In addition, pharmacotherapy for KD/HTS is sometimes combined with surgical excision and/or with physical therapy such as cryotherapy, laser therapy, radiotherapy including brachytherapy, and silicone gel/sheeting. The results regarding the clinical effectiveness of each mono-pharmacotherapy for KD/HTS are not always consistent but rather scattered among researchers. Multimodal combination pharmacotherapy that targets multiple sites simultaneously is more effective than mono-pharmacotherapy. The literature was searched using PubMed, Google Scholar, and Online search engines.

The primary objective of this study is to examine the efficiency of various regenerative medicine approaches, such as platelet-rich plasma, cell therapy, stromal vascular fraction, exosomes and stem cell-conditioned medium, in the process of healing hypertrophic and keloid scars. Major databases including PubMed, Scopus and Web of Science were systematically searched, and based on the content of the articles and the inclusion and exclusion criteria, eight articles were selected. Out of these eight articles, there were two non-randomized clinical trial studies (25%), one randomized, single-blinded comparative study (12.5%), one retrospective clinical observational study (12.5%) and four randomized clinical trial studies (50%). We employed EndNote X8 and Google Sheets to conduct article reviews and extract relevant data. Following the review phase, the studies underwent analysis and categorization. In all eight reviewed studies, the effectiveness of regenerative medicine in treating hypertrophic scars and keloids has been proven. Out of these studies, five (62.5%) focused on the effectiveness of platelet-rich plasma, two study (25%) examined the effectiveness of stromal vascular fraction and one study (12.5%) explored the efficacy of stem cell-conditioned medium. In two studies (25%), the treatment methods were added to standard treatment, while in six studies (75%), regenerative medicine was used as the sole treatment method and compared with standard treatment. The use of these treatment methods did not result in any serious side effects for the patients. Regenerative medicine is an effective method with minimal side effects for the treatment of hypertrophic scars and keloids. It can be used as a monotherapy or in combination with other treatment methods. However, further studies are needed to thoroughly evaluate the effectiveness of all sub-branches of this method., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Hypertrophic scars can have significant and far-reaching effects on patients that range from itching to creating difficulty with mobility, all of which can negatively impact the individual's quality of life. A recent study showed that many patients with recent scars report pain, burning, pruritus, erythema, in combination with psychological difficulties that impact bodily movement, choice of clothing, and participation in leisure activities. Botulinum toxin Type A (BoNTA) and intense pulsed light (IPL) have shown promise in treating such scars. We propose a novel treatment protocol involving a 4-week intervention with hyperdiluted BoNTA injections and supplemental treatment with IPL for erythema, and a 6-month scar scale assessment and photographic documentation that occurs before and 6 months after treatment. We report four cases where using hyperdiluted BoNTA, either alone or in conjunction with IPL, substantially reduced scar size, improved overall scar appearance, and diminished erythema in areas on the face and the breasts. Although this report suggests that a schedule of alternating treatments with BoNTA and IPL may be beneficial in reducing scar size and enhancing appearance, further research is necessary to better understand the most effective dosages, the relationship between BoNTA and IPL, and the optimal management of scarring., Competing Interests: Conflict of Interest: Mike Clague is a former employee and consultant for Allergan and has worked with Galderma, Croma Pharma, and Hugel Aesthetics as a neurotoxin trainer and consultant. Dr. Greg Goodman is on the Allergan and Galderma Advisory Board and is the owner of Facecoach. Cindy Taing and Lauren Stuart are trainers with Facecoach. Dr. John Delaney is the cofounder and director of Fresh Clinics, a specialist medical supervision business for nonsurgical cosmetic procedures. Dr. John Holbrook is the cofounder and director of Fresh Clinics and is a member of Allergan's Scientific Advisory Panel in Australia. The other authors report no conflicts of interest., (Copyright © 2024 International Society of Plastic and Aesthetic Nurses. All rights reserved.)

Pathologic scars include keloids and hypertrophic scars due to abnormal wound healing. Both cause symptoms of itching and pain; they also affect one's appearance and may even constrain movement. Such scars place a heavy burden on the individual's physical and mental health; moreover, treatment with surgery alone is highly likely to leave more scarring. Therefore, there is an urgent need for a treatment that is both minimally invasive and convenient. Photodynamic therapy (PDT) is an emerging safe and noninvasive technology wherein photosensitizers and specific light sources are used to treat malignant tumors and skin diseases. Research on PDT from both the laboratory and clinic has been reported. These findings on the treatment of pathologic scars using photosensitizers, light sources, and other mechanisms are reviewed in the present article., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the author, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hypertrophic scar (HS) is characterized by an abnormal fibroblast-myofibroblast transformation; non-apoptosis of fibroblasts; and redundant expression of TGF-β1, VEGF, α-SMA, and collagen I/III. An HS affects patients' physical and psychological quality of life, leading to joint dysfunction and skin cancer. However, there is currently no satisfactory drug to treat this disorder. In this study, we constructed methylprednisolone sodium succinate (MPSS) encapsulated ZIF-90 (MPSS@ZIF-90) for the effective treatment of an HS. The encapsulation of MPSS in ZIF-90 can achieve the controllable drug release of MPSS and prolong its effective treatment time. MPSS@ZIF-90 enhanced the apoptosis of human hypertrophic scar fibroblasts and downregulated the overexpression of TGF-β1, VEGF, α-SMA, and collagen I/III both in vitro and in vivo . The instant injection of MPSS@ZIF-90 effectively intervened with the formation of the HS after 28 days. On the contrary, MPSS@ZIF-90 greatly reduced the HS with two injections and 14 days of treatment after the HS was formed. This work provides evidence of effective intervention in the formation of an HS and the therapeutic effectiveness of MPSS@ZIF-90 with short treatment periods in vivo . It suggests that MPSS@ZIF-90 can be used as a biomedical option in the treatment of skin wounds and may reveal the potential molecular basis for promising future antifibrotic agents against scarring.

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application., (© 2024. The Author(s).)

A meta-analysis was conducted to comprehensively evaluate the prophylactic and therapeutic efficacy of botulinum toxin type A (BTX-A) in the treatment of facial hypertrophic scars. Computerised searches were performed in databases, from their inception to November 2023, including Embase, Google Scholar, Cochrane Library, Wanfang, PubMed and China National Knowledge Infrastructure databases, focusing on randomised controlled trials (RCTs) that investigated the use of BTX-A for treating facial hypertrophic scars. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Seventeen RCTs were ultimately included, involving 1605 patients who underwent facial cosmetic surgery. The analysis revealed that compared with conventional treatments, BTX-A significantly reduced visual analogue scale (VAS) scores (standardized mean difference [SMD]: -3.50, 95% confidence interval [CI]: -5.16 to -1.84, p < 0.001) and Vancouver scar scale (VSS) scores (SMD: -2.86, 95% CI: -4.03 to -1.68, p < 0.001), and narrowed scar width (SMD: -1.80, 95% CI: -2.48 to -1.13, p < 0.001), while also enhancing the overall effectiveness of the treatment. This study indicates that BTX-A is an effective modality in the prophylaxis and treatment of facial hypertrophic scars, significantly alleviating scar-related pain and preventing scar widening, and is thus worthy of broader clinical application., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined., Objective: The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids., Materials and Methods: In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded., Results: In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%)., Conclusion: The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars., Competing Interests: Hong Liang Tey is supported by the Clinician Scientist Award (CSAINV20nov-0003) from the National Medical Research Council of Singapore. Yong Yao Chun, Timothy TY Tan and Hong Liang Tey are co-founders of a company (RNAscence Biotech Pte Ltd) that develops silencing RNA-based products for skin applications.

Background: Patients with hypertrophic scars (HSs) or keloids occasionally have epidermoid cysts (ECs), and the effect of ECs on the effectiveness of intralesional corticosteroids (ILCs) treatment in these patients has not been reported., Objective: This study aims to evaluate the influence of ECs on the outcomes of ILCs treatment in patients with HSs or keloids., Materials and Methods: This prospective study included 572 patients with keloids ( n = 461) or HSs ( n = 111). Patients received intralesional triamcinolone acetonide injection (0.05 mL/injection) at a concentration of 40 mg/mL and every 28 days for 4 sessions, with a 1-year follow-up., Results: A higher incidence of ECs was observed in keloid patients (16.92%) compared with HSs patients (7.21%). Keloid patients with ECs were older ( p = .008) and had a longer disease duration ( p = .0148), higher Vancouver scar scale (VSS) scores ( p = .04), and greater thickness ( p = .006). Keloid patients with ECs showed less improvement in VSS scores ( p < .0001) and thickness ( p < .0001) after ILCs treatment, with a higher recurrence rate ( p < .0001). The overall complication rate in keloid patients with ECs after ILCs treatment was 49.51%., Conclusion: Epidermoid cysts under keloids were associated with a poor response to ILCs therapy. Therefore, it is recommended to incorporate ultrasonography as a routine examination for keloid patients to aid in better decision making in clinical practice., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls., Methodology: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO 2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Šídák's multiple comparisons test was used to compare groups., Results: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment., Conclusion: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation., (© 2024 Wiley Periodicals LLC.)

Background: Hypertrophic scars, an abnormal wound-healing response to burn injuries, are characterized by massive fibroblast proliferation and excessive deposition of extracellular matrix and collagen. 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is a promising therapy for hypertrophic scar, details of the mechanisms remain to be elucidated. In this study, we aimed to investigate the molecular mechanisms involved in ALA-PDT against hypertrophic scar fibroblasts., Methods: The morphologies of hypertrophic scar fibroblasts (HSFs) treated with ALA-PDT were observed under a light microscopy. The viability of HSFs was detected using the CCK-8 assay. HSFs-populated collagen gel contraction assays were conducted to examine the fibroblast contractility and the cytotoxicity of HSFs in 3D collagen tissues were observed using confocal microscopy. The effect of ALA-PDT on TGF-β1/Smad2/3/4 signaling pathway activation and effector gene expression were verified by immunoprecipitation, western blot and real-time quantitative PCR analysis., Results: We observed significant changes in cell morphology after ALA-PDT treatment of HSFs. As ALA concentration and light dose increased, the viability of HSFs significantly decreased. ALA-PDT can significantly alleviate the contractile capacity and promote the death of HSFs induced by TGF-β1 treatment in a three-dimensional collagen culture model. TGF-β1 treatment of HSFs can significantly induce phosphorylation of Smad2/3 (p-Smad2/3) in whole cells, as well as p-Smad2/3 and Smad4 proteins into the nucleus and increase the mRNA levels of collagen 1/3 and α-SMA. ALA-PDT hampers the TGF-β1-Smad2/3/4 signaling pathway activation by inducing K48-linked ubiquitination and degradation of Smad4., Conclusions: Our results provide evidence that ALA-PDT can inhibit fibroblast contraction and promote cell death by inhibiting the activation of the TGF-β1 signaling pathway that mediates hypertrophic scar formation, which may be the basis for the efficacy of ALA-PDT in the treatment of hypertrophic scars., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Hypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re-epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu-TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu-TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5-fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co-delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu-TSs not only promote macrophage phenotype-switching to inhibit inflammation by interleukin-related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen-related pathways. Therefore, TA/Fu-TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype-switching and anti-fibrosis effect., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Hypertrophic scars and keloids are common fibroproliferative diseases following injury. Patients with pathologic scars suffer from impaired quality of life and psychological health due to appearance disfiguration, itch, pain, and movement disorders. Recently, the advancement of hydrogels in biomedical fields has brought a variety of novel materials, methods and therapeutic targets for treating hypertrophic scars and keloids, which exhibit broad prospects. This review has summarized current research on hydrogels and loaded components used in preventing and treating hypertrophic scars and keloids. These hydrogels attenuate keloid and hypertrophic scar formation and progression by loading organic chemicals, drugs, or bioactive molecules (such as growth factors, genes, proteins/peptides, and stem cells/exosomes). Among them, smart hydrogels (a very promising method for loading many types of bioactive components) are currently favoured by researchers. In addition, combining hydrogels and current therapy (such as laser or radiation therapy, etc.) could improve the treatment of hypertrophic scars and keloids. Then, the difficulties and limitations of the current research and possible suggestions for improvement are listed. Moreover, we also propose novel strategies for facilitating the construction of target multifunctional hydrogels in the future., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 Zhong et al.)

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

Background: Hypertrophic scar (HS) that can lead to defects in appearance and function is often characterized by uncontrolled fibroblast proliferation and excessive inflammation. Curcumin has been shown to have anti-inflammatory and anti-oxidative effects and to play an anti-fibrotic role by interfering transforming growth factor-β1 (TGF-β1)/Smads signaling pathways., Aim: To study the effect and mechanism of curcumin on HS from the perspective of fibroblast activity and inflammation regulation., Methods: Cell proliferation, migration and the expression of α-smooth muscle actin (α-SMA) of TGF-β1-induced human dermal fibroblasts (HDFs) treated by curcumin were evaluated using Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, Transwell assay, Western blotting and immunofluorescence, respectively. The expression of TGF-β1/Smad3 pathway-related molecules (TGF-β1, TGFβ-R1/2, p-Smad3, Smad4) was detected by Western blotting. In a rabbit ear model, hematoxylin and eosin and Masson's staining were conducted to assess scar elevation and collagen deposition, and immunohistochemistry was performed to detect the activation of fibroblasts and infiltration of inflammatory cells., Results: Curcumin inhibited proliferation, migration and α-SMA expression of HDFs in a dose-dependent manner. Curcumin (25 μm mol/L) did not regulate the expression of endogenous TGF-β1, but suppressed Smad3 phosphorylation and nuclear translocation, leading to lower α-SMA expression. Curcumin also reduced hypertrophic scarring of rabbit ear, accompanied by the inhibited TGF-β1/Smad3 pathway, inflammatory infiltration and M2 macrophage polarization., Conclusion: Curcumin plays an anti-scar role through regulating fibroblast activation and tissue inflammation. Our findings provide scientific reference for the clinical use of curcumin in the treatment of HS., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Traditional medicine believes that hypertrophic scar (HS) falls into the category of "blood stasis". Chinese herbs for promoting blood circulation and removing blood stasis, activating meridians, and relieving pain are usually selected to treat HS by traditional Chinese medicine (TCM). Both Semen Persicae (SP) and Flos Carthami (FC) are confirmed to be effective for HS. Clinically, SP and FC are often used in combination with each other. However, the pharmacodynamic mechanism and molecular target of SP-FC in the treatment of HS are still unclear. Therefore, this study is intended to explore the mechanism and target of SP-FC in the treatment of HS through network pharmacology combined with in vitro cell and molecular biology experiments. Target genes of SP-FC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and targets of HS-related diseases were searched from databases such as Disgenet and GeneCards. Based on the targets searched and obtained, a Venn diagram was plotted to acquire common targets of SP-FC-HS. Next, STRING 11.0 was employed for protein-protein interaction (PPI) network analysis of common targets; and cytoscape 3.9.0 for connection relationship analysis of PPI and plotting of a "drug-component-target" network diagram. Besides, a modified explant culture method was applied to separate primary hypertrophic scar fibroblasts (HSFs); MTT assay to detect cell viability of HSFs after treatment by SP-FC for 24 h; Annexin V-FITC/PI double staining combined with flow cytometry to test apoptosis; western blot to check the protein expression level of p53; and real-time fluorescence quantitative PCR to determine mRNA level of p53. In the analysis of network pharmacology, 269 pharmacological targets of SP, 449 pharmacological targets of FC, and 2569 targets of HS-related diseases were screened from the databases. After plotting the Venn diagram, 116 common targets of SP-FC-HS were acquired. In vitro experiments showed that the expression of p53 in HSFs was decreased. SP-FC significantly reduces the viability of HSFs, increases p53 levels in HSFs, and promotes apoptosis. SP-FC can reduce scar formation by promoting p53 expression., (© 2023 John Wiley & Sons Ltd.)

Background: Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia., Objective: We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars., Methods: A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction., Results: Six female patients and five male patients aged 5-17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were 'satisfied' and five patients were 'very satisfied' with the treatment., Conclusions: Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Injury to the skin can cause abnormal wound healing and continuous inflammation that leads to the formation of hypertrophic scars and keloids. These lesions often cause significant negative impact on a patient's life due to aesthetic, physical, social, and psychological consequences. Numerous treatment modalities exist for these hypertrophic scars and keloids, which include silicone sheeting, pressure garments, intralesional injection/topical application of scar-modulating agents, laser therapy, and surgical excision. Due to increased efficacy, an evolving treatment paradigm encourages the use of multiple treatment modalities instead of one treatment modality. However, no gold standard treatment exists for these lesions, leaving many people with unsatisfactory results. Adding scar-modulating agents such as 5-Fluorouracil, bleomycin, or Botulinum Toxin A to triamcinolone monotherapy has emerged as a potential drug combination for treating hypertrophic scars and keloids. We sought to critically analyze the evidence that exists for the use of more than one scar-modulating agent. This was done by conducting a systematic review to determine the efficacy of these combined drug regimens. We found that many of these combinations show evidence of increased efficacy and fewer/similar adverse events to triamcinolone monotherapy. Triamcinolone and 5-Fluorouracil showed the strongest and most consistent evidence out of all combinations. With this review, we intend to encourage more research into unique drug combinations that may improve outcomes for patients with symptomatic hypertrophic scars or keloids., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Hypertrophic scar (HS) is a fibrotic skin condition and characterized by abnormal proliferation of myofibroblasts and accumulation of extracellular matrix. Melatonin, an endogenous hormone, can alleviate fibrosis in multiple models of diseases. This study examined the effect of melatonin on fibrosis in primary fibroblasts from human HS (HSFs) and a rabbit ear model and potential mechanisms. Melatonin treatment significantly decreased the migration and contraction capacity, collagen and α-smooth muscle actin (α-SMA) production in HSFs. RNA-sequencing and bioinformatic analyses indicated that melatonin modulated the expression of genes involved in autophagy and oxidative stress. Mechanistically, melatonin treatment attenuated the AKT/mTOR activation through affecting the binding of MT2 receptor with PI3K to enhance autophagy, decreasing fibrogenic factor production in HSFs. Moreover, melatonin treatment inhibited HS formation in rabbit ears by enhancing autophagy. The anti-fibrotic effects of melatonin were abrogated by treatment with an autophagy inhibitor (3-methyladenine, 3-MA), an Akt activator (SC79), or an MT2 selective antagonist (4-phenyl-2propionamidotetralin, 4-P-PDOT). Therefore, melatonin may be a potential drug for prevention and treatment of HS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was supported by the grants from the National Natural Science Foundation of China (82272273, 82072181, 81972569, 81772925), the Sun Yat-sen University Clinical Research 5010 Program (grant number 2018003)., (Copyright © 2023. Published by Elsevier B.V.)

Hypertrophic scars and keloids are characterized by an excessive collagen deposition. The available treatment options are invasive and can result in recurrence of scar formation. Using liposomes and transferosomes for the topical delivery of papain, a proteolytic enzyme, can be effective treatment. The objective of the study is to formulate papain-loaded liposomes and transferosomes, characterize the formulations, and study in vitro permeation using shed snake skin and Sprague-Dawley rat skin as models for stratum corneum and full thickness skin. Papain-loaded liposomes and transferosomes were formulated using the thin-film hydration method for the delivery of papain across the stratum corneum barrier. An in vitro permeation study carried out using shed-snake skin and Sprague-Dawley rat skin models showed that transferosomes were able to deliver papain across the stratum corneum barrier, while papain solution and papain liposomes were not able to cross the barrier. However, transferosomes were not able to deliver papain across the full thickness rat skin model suggesting the deposition of papain loaded transferosomes in the epidermal or dermal layer of skin. In addition, an ex-vivo model was used to analyze the effect of papain exposure on the morphology of the epidermis taken from rat skin exposed to papain solution, papain in transferosomes and papain in liposomes. Papain in solution resulted in a noticeable degradation of the epidermis, but when embedded in either transferosomes or liposomes there was no noticeable change when compared to control animals. The cytotoxicity study performed using HeLa cells showed that the cells were viable at papain concentrations lower than 0.01 mg/ml., Competing Interests: Authors have no competing interest exist, (Copyright: © 2023 Sapkota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hypertrophic scars (HTS) and keloids are pathologic scars that are products of a wound healing pathway error attributed to genetic and inflammatory causes (Leventhal et al., Arch Facial Plast Surg 8(6):362-368. https://doi.org/10.1001/archfaci.8.6.362 , 2006). Methods of pathologic scar treatment include intralesional agents, cryotherapy, surgical excision, pressure dressings, topical agents, laser resurfacing, radiotherapy, and other investigational therapies (Leventhal et al. 2006). The recurrence of pathologic scar is high across all treatment modalities, including the use of intralesional agents (Trisliana Perdanasari et al., Arch Plast Surg 41(6):620-629. https://doi.org/10.5999/aps.2014.41.6.620 , 2014). In the treatment of pathologic scar, combination approaches using intralesional agents, such as triamcinolone (TAC), 5-fluorouracil (5FU), verapamil (VER), bleomycin (BLM), and botulinum toxin (BTX), are superior therapies when compared to monotherapy (Yosipovitch et al., J Dermatol Treat 12(2):87-90. https://doi.org/10.1080/095466301317085363 , 2001; Yang et al., Front Med 8:691628. https://doi.org/10.3389/fmed.2021.691628 , 2021; Sun et al., Aesthetic Plast Surg 45(2):791-805. https://doi.org/10.1007/s00266-019-01570-8 , 2021). This review assesses recurrence and the reporting of recurrence in pathologic scar after treatment with intralesional triamcinolone (TAC) in combination with another intralesional agent. A literature review was conducted using research journals from PubMed using the following search terms: [(keloid) AND (triamcinolone) AND (combination) AND (intralesional)], as well as [(keloid) AND (triamcinolone) AND (combination)]. Articles were reviewed and included if the article analyzed  or compared intralesional agents for pathologic scar treatment within the last 10 years. The average follow-up period of included articles (n = 14) that utilized combination intralesional therapy (TAC-X) was approximately 11 months (range 1-24 months). Consistent recurrence rate reporting across studies was lacking. The combination agent with the highest recurrence rate was TAC-5FU (23.3%). The range of reported recurrence rates was 7.5-23.3%. Six studies using various intralesional combination regimens reported 0% recurrence over the follow-up period (TAC-5FU, TAC-BTX, TAC-BLM, TAC-CRY). Three studies did not report recurrence rates. While the efficacy of combination therapy is typically assessed via scar scales, the assessment of recurrence across studies of combination therapy is inconsistent and inadequate, with truncated follow-up periods. While scar recurrence can take place during 1-year post-treatment, long-term follow-up (18-24 months) is needed to characterize recurrence in the treatment of pathologic scar using various intralesional agents. Long-term follow-up periods allow patients to receive accurate prognostic information regarding recurrence after combination intralesional therapy. There are limitations to this review in that comparisons were made across studies with varying outcome variables, including scar size, injection concentration and interval, and follow-up period. Standardized follow-up periods and recurrence rate reporting are integral to furthering the understanding of these therapies and enhancing patient care., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hypertrophic scars (HS) often affect the normal function and appearance of the skin and bring adverse effects to the body and mind of patients, being a challenge in the fields of burns and plastic surgery as well as rehabilitation. Despite significant efficacy of centella triterpenes cream for treating HS clinically, its pharmacodynamics and molecular targets are still unclear. Therefore, the network pharmacology analysis combined with in vitro cell molecular biology experiments was used to explore the mechanism and targets of centella triterpenes cream treating HS in this study., Methods: First, target genes of asiaticoside (AC) were obtained from the databases including the Comparative Toxicogenomics Database, similarity ensemble approach, SwissTargetPrediction and TargetNet, and HS targets were acquired from the databases like Disgenet, GeneCards, and Online Mendelian Inheritance in Man. The common targets of AC-HS were obtained through plotting a Venn diagram. Subsequently, STRING 11.0 was employed for analyzing the protein-protein interaction (PPI) network of the common targets, and cytoscape 3.9.0 for analyzing the connectivity of PPI and plotting the network diagram of "drug-component-target". Additionally, a modified tissue culture method was applied to separate primary normal fibroblasts (NFs) in human skin and hypertrophic scar fibroblasts (HSFs). HSFs after 24-h AC treatment were subjected to MTT assay to detect cell viability, scratch assay to assess cell migration ability, and western blot to test the protein expression levels of STAT3, p-STAT3, transforming growth factor-β1 (TGF-β1), collagen I (COL 1), fibronectin 1 (FN1), and alpha-smooth muscle actin (α-SMA)., Results: In network pharmacology analysis, 134 pharmacodynamic targets of AC and 2333 HS targets were obtained after retrieving the database, 50 AC-HS common targets were obtained by a Venn diagram, and a total of 178 edges and 13 core genes such as JUN and STAT3 were acquired by PPI analysis. In vitro experiments showed that the phosphorylation level of STAT3 (p-STAT3) was increased in HSFs. In addition to reducing p-STAT3 in HSFs, AC significantly inhibited the cell viability and migration of HSFs and downregulated the protein levels of TGF-β1, COL 1, FN 1, and α-SMA., Conclusion: STAT3 can be activated in HS. AC may exert its pharmacological effects of inhibiting TGF-β1 signal transduction and regulating extracellular matrix remodeling in HS by inhibiting STAT3 phosphorylation. However, the specific molecular mechanism of AC remains to be verified through further experiments., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: In this clinical trial, we investigated the efficacy of two treatment methods for keloids resulting from surgical incisions: intralesional triamcinolone injections alone versus in combination with verapamil., Material and Methods: Patients were divided into two groups: one received triamcinolone alone (Group T) and the other received a triamcinolone-verapamil blend (Group VT). Regular treatments were conducted until the keloids were nearly flat or for a maximum of eight sessions., Results: Both groups showed significant improvements, but Group VT saw quicker resolution of skin redness and needed fewer sessions. Though the Vancouver Scar Scale (VSS) scores were generally similar across both groups, Group VT exhibited greater improvements, leading to lower final scores. The VT group also attained normal scar flexibility faster than the T group., Conclusion: These findings suggest that the combination of verapamil and triamcinolone provides a more effective treatment for keloids, thereby highlighting the potential of verapamil in scar reduction., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Keloids and hypertrophic scars negatively impact the quality of life for millions of people in the world. Unfortunately, though many thera-peutic approaches are used to treat scars, they are often limited in efficacy with high rates of recurrence. Lately, a better understanding of the immune dysregulation of several dermatologic conditions has led to the emergence of multiple cytokine-targeted therapies for numerous conditions. Several studies have implicated T helper 2 (Th2) immune dysregulation in the development of scars and keloids, with interleukins (IL)-4 and -13 identified as pro-fibrotic mediators. Dupilumab is an IL-4 receptor alpha antagonist that inhibits the ex-pression of both IL-4 and -13. Herein, we describe a 44-year-old woman who developed numerous disfiguring hypertrophic scars and keloids after suffering from a severe herpes zoster infection. Given the number of scars, intralesional corticosteroid injections were not feasible. Therefore, treatment with systemic dupilumab was initiated. Many scars flattened, several even developing a cigarette-paper-like texture due to rapid involution. The largest and most recalcitrant keloid was further treated with intralesional dupliumab injec-tions every 2 weeks with an even more dramatic improvement noted in 2 months. To our knowledge, this is the first report of treating multiple keloids and hypertrophic scars with both systemic and intralesional dupilumab. Dermatologists may want to consider treating keloids that cover a large area with systemic dupilumab, a therapy with an established, reassuring safety profile. The most recalcitrant areas may further benefit from concentrating dupilumab by intralesional delivery. J Drugs Dermatol. 2023;22(12):1220-1222.&nbsp; doi:10.36849/JDD.6385.

Background and Objectives : The prevalence of hypertrophic scarring after a burn is approximately 70%. Despite advances in burn management, there is currently no gold standard treatment to reduce or prevent its occurrence. Glucocorticoids are frequently given to patients early after burns for other therapeutic purposes and have been shown to induce scar regression. Therefore, the purpose of the present work is to determine the incidence of hypertrophic scar diagnosis in burn patients who were administered glucocorticoid treatment using TriNetX, a large patient database. Materials and Methods : Patients diagnosed with hypertrophic scarring, hypertrophic disorders of the skin, or scar conditions and fibrosis of the skin after burn injury were identified in the TriNetX database. The glucocorticoids investigated include hydrocortisone, methylprednisolone, dexamethasone, triamcinolone, and prednisone. Patients were stratified into three groups based on total body surface area (TBSA) burned: 0-19%, 20-39%, and 40-100%. The risk ratio was evaluated for burn patients who received varying glucocorticoids after injury based on TBSA burned. Additionally, treatment pathways, time of treatment, and treatment purity pathways were evaluated. Results : In patients with a 0-19% TBSA burn, methylprednisolone showed a decreased risk of developing hypertrophic scar diagnosis. In those with a 20-39% TBSA burn or 40-100% TBSA burn, dexamethasone showed an increased risk of developing hypertrophic scar diagnosis. Additionally, dexamethasone was the most commonly administered glucocorticoid for burn patients and was most likely to be administered earlier after burn injury, comparatively. Conclusions : Methylprednisolone was associated with reduced hypertrophic scar diagnosis in burn patients independent of TBSA burn. While glucocorticoids are one of the mainstay treatments for hypertrophic scarring, further studies are needed to determine early therapeutic interventions that will reduce the potential for hypertrophic scar development in burn patients.

First-line treatment of keloids consists of intralesional needle injections with corticosteroids, but generally entails multiple painful sessions, resulting in variable clinical outcomes. Novel needle-free jet injectors may facilitate more effective and patient-friendly dermal drug delivery. Here, we evaluated the effectiveness, tolerability and patient satisfaction of intralesional triamcinolone-acetonide (TCA) treatment in recalcitrant keloids using an electronically controlled pneumatic injector (EPI). A retrospective study was conducted in recalcitrant keloid patients with a history of severe pain during needle injections who received three sessions of EPI + TCA. Outcome measures included Patient and Observer Scar Assessment Scale (POSAS), Global Aesthetic Improvement Scale (GAIS), treatment-related pain (NRS), adverse effects, and patient satisfaction (survey). Ten patients with in total 283 keloids were included. The POSAS score significantly improved at follow-up and GAIS was reported as '(very) improved' for all patients. EPI + TCA was well-tolerated with a significantly lower NRS pain score compared to needle + TCA (pilot treatment). Only minor adverse effects occurred, and 90% of patients preferred EPI over needle treatment. EPI + TCA is an effective and tolerable treatment for patients with recalcitrant keloids. The minimal treatment-related pain and high patient satisfaction makes it a promising treatment for patients with needle-phobia and/or severe pain during needle injections., (© 2023. The Author(s).)