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Pressure garment therapy is frequently used to prevent pathologic scarring, especially in burns. Less common is its use for the treatment of facial wounds. Pathologic scarring can create functional and aesthetic problems, which can have psychological implications. The aim of this study is to report our experience in the treatment of traumatic facial wounds using an elastic custom facial mask.

Alu elements are retrotransposons related to epigenetic modifications. To date, the role of epigenetics in hypertrophic scars from burn remains unknown. Here, our aim was to examine the pathophysiology of hypertrophic scars from an epigenetic perspective. For that, we performed a cross-sectional analytical study using tissue and blood samples from burned and healthy patients (n = 23 each) to detect Alu methylation levels and patterns. The results of the combined bisulfite restriction analysis technique were categorized into four groups based on the methylation status at the CpG dinucleotides from the 5' to the 3' ends of the Alu sequence: hypermethylated (mCmC), hypomethylated (uCuC), and partially methylated (uCmC and mCuC). Alu methylation levels were significantly lower in hypertrophic scar tissues than in normal skin (29.37 ± 2.49% vs. 35.56 ± 3.18%, p = 0.0002). In contrast, the levels were significantly higher in white blood cells from blood samples of burned patients than in those of control blood samples (26.92 ± 4.04% vs. 24.58 ± 3.34%, p = 0.0278). Alu total methylation (mC) and the uCmC pattern were significantly lower, whereas uCuC was significantly higher, in hypertrophic scar tissues than in normal skin (p < 0.0001). Receiver operating characteristic analysis indicated that the uCmC and uCuC patterns are useful as hypertrophic scar DNA methylation markers after burn, with 91.30% sensitivity and 96.23% specificity and 100% sensitivity and 94.23% specificity, respectively. Our findings suggest that epigenetic modifications play a major role in hypertrophic scar pathogenesis, and may be the starting point for developing a novel technique for burn scar treatment.

Hypertrophic scars and keloids are two different manifestations of excessive dermal fibrosis and are caused by an alteration in the normal wound-healing process. Treatment with radiofrequency (RF)-based therapies has proven to be useful in reducing hypertrophic scars. In this study, the effect of one of these radiofrequency therapies, Capacitive Resistive Electrical Transfer Therapy (CRET) on biomarkers of skin fibrosis was investigated. For this, in cultures of human myofibroblasts treated with CRET therapy or sham-treated, proliferation (XTT Assay), apoptosis (TUNEL Assay), and cell migration (Wound Closure Assay) were analyzed. Furthermore, in these cultures the expression and/or localization of extracellular matrix proteins such as α-SMA, Col I, Col III (immunofluorescence), metalloproteinases MMP1 and MMP9, MAP kinase ERK1/2, and the transcription factor NFκB were also investigated (immunoblot). The results have revealed that CRET decreases the expression of extracellular matrix proteins, modifies the expression of the metalloproteinase MMP9, and reduces the activation of NFκB with respect to controls, suggesting that this therapy could be useful for the treatment of fibrotic pathologies.

RESUMO Introdução: Considerando um número estimado de cerca de 51 milhões de cirurgias a cada ano apenas nos EUA, podemos dizer que a hipertrofia cicatricial é um problema relevante, já que uma cicatriz fina, de boa qualidade, pode ser a linha divisória entre um bom resultado e uma cirurgia malsucedida. O objetivo é fazer uma revisão bibliográfica acerca dos métodos de tratamento não invasivos atualmente disponíveis para a prevenção da hipertrofia cicatricial pós-cirúrgica e discutir a sua eficácia baseada em evidências. Método: Foi realizada uma pesquisa nas bases de dados Pubmed, Lilacs e SciELO, utilizando os termos “scar prevention” and “hypertrophic scars”, por ensaios clínicos, meta-análises e artigos de revisão publicados a partir de 2004, em inglês ou português. Resultados e Conclusões: Foram encontrados vários trabalhos utilizando o silicone, proporcionando alguma evidência acerca da sua eficácia; foram encontrados apenas três ensaios clínicos prospectivos relacionados ao uso do Contractubex®; dois ensaios clínicos prospectivos, controlados, randomizados, sendo apenas um deles duplo-cego, com o imiquimode a 5%; foi encontrado apenas um ensaio clínico bem desenhado utilizando o esparadrapo microporoso e outro trabalho relacionado ao uso da vitamina E, que não mostrou bons resultados; não foram encontrados ensaios clínicos sobre o uso da massagem e da pressão local. Apesar das deficiências dos estudos, o silicone é considerado a primeira opção na prevenção da hipertrofia cicatricial pós-cirúrgica. Não há evidências que comprovem a eficácia do esparadrapo microporoso, da massagem, da pressão local, do Contractubex, do imiquimode a 5% e da vitamina E. ABSTRACT Introduction: Considering that nearly 51 million surgeries are performed annually just in the USA, we can state that scar hypertrophy is a relevant problem, since a thin, good quality scar can be the dividing line between a good outcome and an unsuccessful surgery. The objective is to perform a bibliographic review of the noninvasive methods currently available to prevent postoperative hypertrophic scars and discuss their evidence-based effectiveness. Method: A search was performed in PubMed, LILACS, and SciELO databases, using the terms “scar prevention” and “hypertrophic scars,” for clinical trials, meta-analyses, and review articles published since 2004 in English or Portuguese language. Results and Conclusions: Several studies using silicone were found, providing some evidence on its effectiveness; only 3 prospective clinical trials using Contractubex® were found; 2 controlled, randomized prospective clinical trials using 5% imiquimod were found, but only one was doubleblind; one well-designed clinical trial using a micropore adhesive tape was found; a similar clinical trial using vitamin E did not show good results. Clinical trials on the use of massage and local pressure were not found. Despite the limitations of the studies, silicone is considered the first treatment option for the prevention of postoperative hypertrophic scars. There is no evidence proving the effectiveness of micropore adhesive tape, massage, local pressure, Contractubex, 5% imiquimod, or vitamin E.

▪ RESUMO Introdução: Cicatrizes hipertróficas e queloides causam dano estético e funcional e são de difícil tratamento. O objetivo desta revisão foi identificar estudos prospectivos do tratamento com o laser fracionado de CO2, mostrando as alterações clínicas e histológicas e a metodologia utilizada para a avaliação das cicatrizes antes e após intervenção. Métodos: Foi realizada uma revisão eletrônica (LILACS, Medline e SciELO) de estudos publicados entre janeiro de 2004 e dezembro de 2017, com os termos “keloid/queloide”, “hypertrophic scar/cicatriz hipertrófica” e “laser CO2”, de acordo com o PRISMA Statement, sendo selecionados os estudos que comparassem as cicatrizes antes e depois de tratamento isolado com laser fracionado de CO2. Os dados foram analisados por dois revisores independentes. Resultados: Foram analisados 102 artigos, sendo que 7 cumpriam os critérios estabelecidos. Destes, os 7 analisaram cicatrizes hipertróficas, 2 deles também analisaram queloides, e 3 estudaram alterações histológicas. Houve diferença estatística entre os escores clínicos medidos antes e após tratamento de cicatrizes hipertróficas na maioria dos estudos, com melhora nos sintomas, na flexibilidade e altura da cicatriz. Entre os 2 estudos que analisaram os queloides, 1 deles demonstrou diferença clínica após tratamento. Nas alterações histológicas, houve diferença na orientação e densidade das fibras de colágeno e na espessura da epiderme. Conclusão: O laser fracionado de CO2 deve ser considerado como opção promissora no tratamento de cicatrizes patológicas, visto que melhora os sinais e sintomas clínicos como cor, espessura e prurido. ▪ ABSTRACT Introduction: Hypertrophic scars and keloids cause aesthetic and functional damages, and are difficult to treat. This review aimed to identify prospective studies on fractional CO2 laser to present the clinical and histological changes and the methodology used for the evaluation of scars before and after intervention. Methods: We conducted an electronic review (LILACS, Medline, and SciELO) of studies published between January 2004 and December 2017, using the search terms “keloid/queloide,” “hypertrophic scar/cicatriz hipertrófica,” and “CO laser, ” according to the PRISMA Statement. Studies that compared scars before and after isolated treatment with fractional CO2 laser were selected. Two independent reviewers analyzed the data. Results: One hundred two articles were analyzed, of which 7 met the inclusion criteria. Of the 7 articles, all analyzed hypertrophic scars, 2 analyzed keloids in addition to hypertrophic scars, and 3 analyzed histological changes. Most studies showed a statistically significant difference in clinical scores between before and after treatment of hypertrophic scars, with improvement in symptoms, flexibility, and scar height. Between the 2 studies that analyzed keloids, 1 reported a clinical difference after treatment. The histological changes showed significant differences in the orientation and density of the collagen fibers, and in the thickness of the epidermis. Conclusion: The use of fractional CO2 laser should be considered as a promising treatment option for pathological scars, as it improves clinical signs and symptoms such as color, thickness, and pruritus.

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 μg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.

In this thesis hypergranulation tissue in both the breast after breast implant surgery, as well as in the skin (scar formation) is explored. The histological composition of capsular contracture after breast implant surgery and the role of silicone in this tissue is investigated in multiple papers. Furthermore, the classification used to grade capsular contracture complaints is evaluated. In the second part, the role the systemic immune system has in hypertrophic scarring is examined, and how to use these differences to enable prognostic tools.

Background and objectives Both artesunate and fractional CO2 laser have been proved effective in the treatment of hypertrophic scars, yet little data are available for the efficacy of artesunate combined with fractional CO2 laser. In order to assess the pre-clinical significance and the underlying mechanism of this combined treatment profile, we attempted to observe the effectiveness of this therapy in rabbit models through determining the expression of BMP-7 and Fas. Materials and methods Twenty-Four New Zealand white rabbits with established hypertrophic scar samples were randomly divided into control group and three treatment groups. Artesunate (20 μl/cm2) was injected into the rat’s scar of artesunate and combination groups, while fractional CO2 laser (Combo mode, deep energy:10 mJ, super energy: 50 mJ) was applied to rats in fractional CO2 laser and combination groups at week 4 after model establishment. All rabbits underwent a total of 3 sessions of treatment once every 2 weeks. Histological and immunohistochemistry study, Western blot assay, cell viability, ELISA and RT-QPCR were performed at week 10 to observe the aspects of hypertrophic scar sample changes and expression of BMP-7 and Fas in the scar tissues. Results Compared with control group, hypertrophic scars and the collagen fibers were significantly inhibited after treatment, and higher inhibition was seen in the samples in combination group compared to that in artesunate and fractional CO2 laser groups (P Conclusions Artesunate combined with fractional CO2 laser is effective in hypertrophic scarring in this rabbit model. Our findings can serve as a potential alternative strategy to treatment of hypertrophic scar in clinical practice.

Keloid fibroblasts (KFs) undergo reprogramming of the metabolic phenotype from oxidative phosphorylation to the Warburg effect. However, more studies are needed to demonstrate whether there is a Warburg effect in KFs and to determine whether there is a similar phenomenon in other types of scars or in the proliferative stage of scars. In our study, the mRNA and protein expression of key glycolytic enzymes, glucose consumption and lactate production in KFs, normal skin fibroblasts (NFs), atrophic scar fibroblasts (ASFs), proliferative stage scar fibroblasts (PSSFs), and hypertrophic scar fibroblasts (HSFs) were detected. In addition, the effects of 2-deoxy-d-glucose (2-DG, a glycolysis inhibitor) on cell proliferation in KFs and NFs were studied. We found that the mRNA and protein expression of key glycolytic enzymes in KFs were significantly upregulated compared with those in NFs. Glucose consumption and lactate production in KFs were also higher than that in NFs. However, we found no similar phenomenon in ASFs, PSSFs, or HSFs. When treated with 2mmol/l 2-DG, the cell viability of KFs decreased more than that of NFs. What's more, treatment with increasing concentrations of 2-DG could inhibit cell viability and migration of KFs in a dose-dependent manner. In conclusion, the Warburg effect in KFs is a feature different from ASFs, PSSFs, or HSFs. Keloids are essentially different from other types of scars in terms of energy metabolism. This characteristic of KFs could provide new hope for the early diagnosis and treatment of keloids.

Kartika Ruchiatan,1 Reti Hindritiani,1 Diah Puspitosari,1 Gabriela Reginata,1 Rani Septrina2 1Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia; 2Department of Plastic Surgery and Reconstruction, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, IndonesiaCorrespondence: Kartika RuchiatanDepartment of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Jl. Pasteur 38, Bandung, West Java, 40161, IndonesiaTel +62811247932Email kartika.ruchiatan@unpad.ac.idAbstract: Rhinophyma is characterized by progressive enlargement of the nasal skin, which is considered to be an advanced stage of phymatous rosacea. Esthetic disfigurement makes surgical treatment necessary for this condition. Hypertrophic scars are the consequence of alterations in the skin’s healing process following surgical interventions. Laser may be the treatment of choice in hypertrophic scars. We reported a case of hypertrophic scars following excisional surgery and full-thickness skin grafting due to rhinophyma in an 18-year-old male who was consulted from the Department of Plastic Surgery and Reconstruction. The 1064 nanometer (nm) Q-switched Neodymium: Yttrium Aluminum Garnet (QS Nd:YAG) with 4 mm spot size, 1.5 J/cm2 and 1 Hz was applied to the hypertrophic scars for three sessions within one month interval. Clinical improvement was observed as indicated by the patient’s Vancouver scar scale score and spectrophotometry result, and no side effects were found. Nd:YAG laser is a non-ablative device that targets hemoglobin, water, and melanin. Any thermal effects on dermal tissue containing blood vessels could result in reduced blood flow through the capillaries in the dermal papillae. QS Nd:YAG-induced selective photothermolysis was responsible for collagen breakdown and reduced collagen production in hypertrophic scars. The 1064 nm QS Nd:YAG laser gave good results in this case although more treatment sessions may be recommended and a longer follow-up is necessary in order to assess the stability of the result.Keywords: hypertrophic scar, rhinophyma, QS Nd:YAG laser

Introduction: Mesenchymal stromal cells (MSCs) administration is an effective option for the treatment of diabetic foot ulcers (DFUs). However, to date, studies assessing long-term outcomes and evaluating skin parameters after cell-based therapy are lacking. We presented the clinical outcomes of 3 patients, treated for DFUs with the bone marrow MSCs 3 years earlier. Methods: Ultrasound examination was used to compare collagen density and epidermal thickness in areas of healed ulcers in comparison with non-affected skin used as a control. Ultrasound and dermatoscopy were used to exclude neoplasm formation, to assess scar contracture and wound recurrence. Results: In all patients, no ulcer recurrence was detected, which was lower than the expected 60% rate of re-ulceration in diabetic patients in a 3-year period (OD [odds ratio] = 0.095, P = 0.12). No neoplasm formation, no contracture of hypertrophic scar, and adjacent tissue were registered. Collagen ultrasound density was decreased by 57% (P = 0.053) and epidermal thickness was increased by 72% (P = 0.01) in the area of healed ulcers in all patients. Conclusion: MSCs therapy alone did not result in the complete restoration of the skin parameters within a 3-year period. MSCs may represent important adjuvant to the therapy, however, other novel approaches are required to achieve better results.

Rhinophyma is characterized by progressive enlargement of the nasal skin, which is considered to be an advanced stage of phymatous rosacea. Esthetic disfigurement makes surgical treatment necessary for this condition. Hypertrophic scars are the consequence of alterations in the skin’s healing process following surgical interventions. Laser may be the treatment of choice in hypertrophic scars. We reported a case of hypertrophic scars following excisional surgery and full-thickness skin grafting due to rhinophyma in an 18-year-old male who was consulted from the Department of Plastic Surgery and Reconstruction. The 1064 nanometer (nm) Q-switched Neodymium: Yttrium Aluminum Garnet (QS Nd:YAG) with 4 mm spot size, 1.5 J/cm2 and 1 Hz was applied to the hypertrophic scars for three sessions within one month interval. Clinical improvement was observed as indicated by the patient’s Vancouver scar scale score and spectrophotometry result, and no side effects were found. Nd:YAG laser is a non-ablative device that targets hemoglobin, water, and melanin. Any thermal effects on dermal tissue containing blood vessels could result in reduced blood flow through the capillaries in the dermal papillae. QS Nd:YAG-induced selective photothermolysis was responsible for collagen breakdown and reduced collagen production in hypertrophic scars. The 1064 nm QS Nd:YAG laser gave good results in this case although more treatment sessions may be recommended and a longer follow-up is necessary in order to assess the stability of the result.

Hypertrophic scarring following burn injuries has been shown to occur in up to 70% of patients, potentially causing both long-term psychological and physical morbidity. Increased rates of depression and anxiety are seen to arise from aesthetic dissatisfaction, affecting patient rehabilitation and subsequent societal interaction. Mobility is jeopardized from contractures that develop within the damaged tissue, leading to decreased range of motion and function of the area. Both sequelae leave the patient with an overall decreased quality of life. Surgical techniques involving local tissue rearrangement, including Z-plasty and VY-plasty can be employed to improve both the function and cosmetic effects of burn scars. Essentially, these techniques illicit a decrease in tension through a lengthening of contracted tissue of up to 50–70%, allowing for better static alignment and increased mobility over joint surfaces. This video depicts the combination of both tissue rearrangement techniques as applied to hypertrophic scar contractures resulting from prior burn injuries. The authors find these techniques an invaluable part of a reconstructive surgeons armamentarium when approaching scar revision.

In vitro research in the field of mechanotransducive regulation of dermal fibroblasts is characterized by highly variable methodology and contradictory results. The primary objective of this systematic review was to establish how in vitro mechanical stretch affects human dermal fibroblast function, by means of a quantitative synthesis of all available evidence. The secondary objectives were to examine the effects of covariates related to donor age, fibroblast origin, experimental treatments, and mechanical stimulation parameters on dermal fibroblast responsiveness to mechanical strain. Summary outcomes for fibroblast proliferation and collagen production were combined using a fixed-effects meta-analytical model. Subgroup analysis and meta-regression were used to investigate the effects of different conditions on the summary outcomes. Mechanical strain was found to not affect fibroblast proliferation in neonatal fibroblasts, while adult fibroblasts proliferation was significantly increased. Collagen production was significantly increased in response to mechanical stimulation, with Vitamin C stimulation as the most important covariate. Stretching frequency emerged as positively associated with fibroblast proliferation and negatively associated with collagen production. We conclude from this study that distinct differences exist in the effects of mechanical stretching between dermal fibroblasts from neonatal and adult donors, which will help to further elucidate the pathophysiological mechanism behind tension-induced scarring.

Background Postsurgical scar management significantly affects patient satisfaction. However, reliable skin support options are limited. Objectives The present study aimed to determine the efficacy and safety of using tissue adhesive zippers in postsurgical scar prevention among patients undergoing surgical excision of the face. The primary outcome was a reduction in scar width, which was evaluated 1, 3, 6, and 12 months postoperatively. Scar width at Month 12 was considered the final outcome. Methods This was a prospective, randomized, controlled, rater-blinded trial. Sixty-four patients were randomly assigned to 2 groups (the zip group, defined as those using a tissue adhesive zipper for 3 months after surgery, and the control group). Outcomes were evaluated 1, 3, 6, and 12 months postoperatively based on scar width and Patient Observer Scar Assessment Scale score. Skin irritation was monitored during the first 3 months after surgery. The incidence of hypertrophic scar formation was recorded at a 12-month follow-up. Results Scar width differed significantly between the zip (mean [standard deviation], 1.68 [0.45] mm) and control groups (2.15 [0.64] mm). The scars spread rapidly in the first month after surgery but slowed down and stabilized after 6 months. The Patient Observer Scar Assessment Scale scores of the zip group were significantly lower than those of the control group. Neither group experienced significant complications. Conclusions Prolonged use of tissue adhesive zippers immediately after surgery reduced scar width and improved scar appearance without obvious side effects. Level of Evidence: 2

The effects of long non-coding RNAs (lncRNAs) on the proliferation of hypertrophic scars have been described, however, the underlying mechanisms are not well characterized. The present study aimed to investigate the mechanisms of lncRNA H19 in hypertrophic scars. The effects of the lncRNA H19 on the proliferation and apoptosis of hypertrophic scar fibroblasts (HSFs) were analyzed using 5′-ethynyl-2′-deoxyuridine staining, flow cytometry, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The results revealed H19 promoted the proliferation and inhibited the apoptosis in HSF. In addition, the binding associations between H19 and microRNA-194 (miR-194), and miR-194 and insulin-like growth factor I receptor (IGF1R) were identified using bioinformatics screening and verified using dual-luciferase assays. Furthermore, the effects of the IGF1R knockdown on H19-induced HSF phenotypes and regulation over the p38 MAPK pathway were determined. Mechanistically, miR-194 was identified as the downstream effector of the H19-mediated phenotypes of HSFs through its ability to directly target IGF1R, thus modulating the p38 MAPK signaling pathway. In conclusion, the findings suggested that H19 may inhibit the apoptosis and promote the proliferation of HSFs through the miR-194/IGF1R/p38 MAPK signaling axis, thereby contributing to the progression of hypertrophic scars. These findings may provide novel targets for the treatment of hypertrophic scars.

The excessive healing response during wound repair can result in hypertrophic scars (HS). Lysyl oxidase like 1 (LOXL1) has been reported to be associated with fibrosis via targeting transforming growth factor β1 (TGF-β1) signaling. This study aimed to investigate the effect of LOXL1 on HS formation. The expression of LOXL1 in HS tissues and TGF-β1-induced HS-derived fibroblasts (HSFs) was detected via reverse transcription quantitative PCR and Western blot. LOXL1 was silenced in HSFs using transfection with short hairpin RNA (shRNA), then wound healing process including cell proliferation, cell cycle distribution, migration, and extracellular matrix (ECM) deposition along with Smad expression were measured by cell counting kit-8, EdU staining, flow cytometry, transwell, immunofluorescence, and Western blot assays. LOXL1 was upregulated in HS tissues and TGF-β1-induced HSFs. Knockdown of LOXL1 inhibited proliferation and migration but promoted cell cycle G0/G1 phase arrest in TGF-β1-induced HSFs; it increased expression of cyclin D1, CDK4, MMP2, MMP9, COL1A1, COL1A2, fibronectin, COL3A1, α-SMA, but decreased expression of p27, and the phosphorylation of Smad2 and Smad3 caused by TGF-β1 were also blocked by LOXL1 silencing. Silence of LOXL1 could effectively inhibit TGF-β1-induced proliferation, migration, and ECM deposition in HSFs via inactivating Smad pathway. Targeting LOXL1 may have future therapeutic implications for HS treatment.

Introduction Curettage and dermabrasion are effective in the treatment of giant congenital melanocytic nevi (GCMN); however, local infection and hypertrophic scar formation are major issues. Thus, we applied cultured epithelial autografts (CEA) on skin defects after curettage or abrasion of GCMN and assessed the postoperative outcomes. Methods Seven nevi lesions of five patients (aged 3 months to 24 years) were treated with CEA after curettage or abrasion with a dermatome or a surgical bar, respectively. We assessed the postoperative outcomes, including CEA take ratio, erosion and/or ulcer formation in the acute phase, hospitalization days, Vancouver scar scale, and color improvement one year after the operation. In addition, a histological evaluation of a skin biopsy was performed over one year after the operation. Results The CEAs took well on the wound, and the wound surface was mostly epithelized by postoperative day 7 in all cases. While hypertrophic scar formation and slight pigmentation were observed in some lesions, the color was improved in all of the treated lesions. Histopathological examination revealed that the regenerated epidermis had stratified keratinocytes with rete ridges, and the dermal layer without nevus cells regenerated above the remaining dermis layer. Conclusions In this study, we found that early epithelialization and regeneration of the dermal layer was achieved after the application of CEA, suggesting that CEA could be an effective option after curettage or abrasion of GCMN., Highlights • Cultured epithelial autograft (CEA) application is effective in the treatment of giant congenital melanocytic nevi. • The grafted CEA takes well on skin defects post curettage and abrasion. • CEAs can achieve rapid epithelization. • Normal dermal tissue regenerates after CEA application.

Introduction: Giant congenital melanocytic nevus (GCMN) is a large melanocytic nevus, and its full-thickness removal is usually difficult due to the lack of skin available for reconstruction. Curettage is an alternative approach in cases of GCMN to remove the superficial dermis above the cleavage plane with a curette in the neonatal period, and its major complications include repigmentation, retarded epithelization, and hypertrophic scar formation. In Japan, the JACE® cultured epidermal autograft (CEA) was approved and covered by public healthcare insurance for the treatment of congenital melanocytic nevus (CMN) that is difficult to treat with conventional methods in 2016. We have used CEA for wounds after curettage in the neonatal period or following ablation after the neonatal period in combination with laser therapies to reduce the above-mentioned complications. Methods: In this study, we summarized all consecutive CMN patients treated using CEA from December 2016 to April 2019 and evaluated the duration required for epithelialization, incidence of hypertrophic scar, and color change in the target nevus by comparing the L∗ values one year later between the Curettage group, the non-Curettage group with initial treatment or the subsequent group. Results: No significant differences were seen in the epithelization period or incidence of hypertrophic scars among the groups, but the color of the target nevus was improved significantly in the Curettage group (p

Hypertrophic scars continue to be a major burden, especially after burns. Persistent inflammation during wound healing appears to be the precipitating aspect in pathologic scarring. The lack of a standardized model hinders research from fully elucidating pathophysiology and therapy, as most therapeutic approaches have sparse evidence. The goal of this project was to investigate the mechanisms of scar formation after prolonged wound inflammation and to introduce a method for generating standardized hypertrophic scars by inducing prolonged inflammation. Four wound types were created in Duroc pigs: full-thickness wounds, burn wounds, and both of them with induced hyperinflammation by resiquimod. Clinical assessment (Vancouver Scar Scale), tissue oxygenation by hyperspectral imaging, histologic assessment, and gene expression analysis were performed at various time points during the following five months. Native burn wounds as well as resiquimod-induced full-thickness and burn wounds resulted in more hypertrophic scars than full-thickness wounds. The scar scale showed significantly higher scores in burn- and resiquimod-induced wounds compared with full-thickness wounds as of day 77. These three wound types also showed relative hypoxia compared with uninduced full-thickness wounds in hyperspectral imaging and increased expression of HIF1a levels. The highest number of inflammatory cells was detected in resiquimod-induced full-thickness wounds with histologic features of hypertrophic scars in burn and resiquimod-induced wounds. Gene expression analysis revealed increased inflammation with only moderately altered fibrosis markers. We successfully created hypertrophic scars in the Duroc pig by using different wound etiologies. Inflammation caused by burns or resiquimod induction led to scars similar to human hypertrophic scars. This model may allow for the further investigation of the exact mechanisms of pathological scars, the role of hypoxia and inflammation, and the testing of therapeutic approaches.

Background: As a fibrotic disease with a high incidence, the pathogenesis of hypertrophic scarring is still not fully understood, and the treatment of this disease is also challenging. In recent years, human adipose-derived mesenchymal stem cells (AD-MSCs) have been considered an effective treatment for hypertrophic scars. This study mainly explored whether the therapeutic effect of AD-MSCs on hypertrophic scars is associated with oxidative-stress-related proteins. Methods: AD-MSCs were isolated from adipose tissues and characterized through flow cytometry and a differentiation test. Afterwards, coculture, cell proliferation, apoptosis, and migration were detected. Western blotting and a quantitative real-time polymerase chain reaction (qRT–PCR) were used to detect oxidative stress-related genes and protein expression in hypertrophic scar fibroblasts (HSFs). Flow cytometry was used to detect reactive oxygen species (ROS). A nude mouse animal model was established; the effect of AD-MSCs on hypertrophic scars was observed; and hematoxylin and eosin staining, Masson’s staining, and immunofluorescence staining were performed. Furthermore, the content of oxidative-stress-related proteins, including nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), B-cell lymphoma 2(Bcl2), Bcl2-associated X(BAX) and caspase 3, was detected. Results: Our results showed that AD-MSCs inhibited HSFs’ proliferation and migration and promoted apoptosis. Moreover, after coculture, the expression of antioxidant enzymes, including HO-1, in HSFs decreased; the content of reactive oxygen species increased; and the expression of Nrf2 decreased significantly. In animal experiments, we found that, at 14 days after injection of AD-MSCs into human hypertrophic scar tissue blocks that were transplanted onto the dorsum of nude mice, the weight of the tissue blocks decreased significantly. Hematoxylin and eosin staining and Masson’s staining demonstrated a rearrangement of collagen fibers. We also found that Nrf2 and antioxidant enzymes decreased significantly, while apoptotic cells increased after AD-MSC treatment. Conclusions: Our results demonstrated that AD-MSCs efficiently cured hypertrophic scars by promoting the apoptosis of HSFs and by inhibiting their proliferation and migration, which may be related to the inhibition of Nrf2 expression in HSFs, suggesting that AD-MSCs may provide an alternative therapeutic approach for the treatment of hypertrophic scars.

Hypertrophic scars and keloids mostly develop as a result of wound healing and skin burns. Depending on their location, pathological scars can be not only aesthetically distressing, but also present challenges associated with limited function of the limbs, frequent trauma, inflammation, and persistent pain syndrome. The urgency of the problem of hypertrophic and keloid scars has led to a plethora of therapeutic strategies and innovation techniques to prevent or attenuate pathological scar formation. At the same time, preventing pathological scarring is undoubtedly more effective and cheaper than treating it later on. Next to surgical techniques, injection therapy and an appropriate general postsurgical care for fresh wounds, a multitude of topical drugs are now available for scareless wound healing. Parallel to various silicone-based products, onion extract or cepalin has been highlighted as one of the potential anti-scarring agents over recent years. Based on several studies, onion extract alone or in combination with allantoin and heparin helped to alleviate the woundhealing process in wounds of various origins and prevent their pathological scarring. Considering that hypotrophic scar and keloid formation following surgery or trauma is almost impossible to predict, it is advisable to actively use topical dosage forms to improve wound healing and minimize aesthetic defect, the more so as the prevention of pathological scarring is more effective, safe and comfortable than its treatment. The simplicity of their use opens up vast opportunities for the treatment and prevention of the pathological scar formation in outpatient practice.

Background Wound healing can result in various outcomes, including hypertrophic scar (HTS). Pigs serve as models to study wound healing as their skin shares physiologic similarity with humans. Yorkshire (Yk) and Duroc (Dc) pigs have been used to mimic normal and abnormal wound healing, respectively. The reason behind this differential healing phenotype was explored here. Methods Excisional wounds were made on Dc and Yk pigs and were sampled and imaged for 98 days. PCR arrays were used to determine differential gene expression. Vancouver Scar Scale (VSS) scores were given. Re‐epithelialization was analyzed. H&E, Mason's trichrome, and immunostains were used to determine cellularity, collagen content, and blood vessel density, respectively. Results Yk wounds heal to a “port wine” HTS, resembling scarring in Fitzpatrick skin types (FST) I‐III. Dc wounds heal to a dyspigmented, non‐pliable HTS, resembling scarring in FST IV–VI. Gene expression during wound healing was differentially regulated versus uninjured skin in 40/80 genes, 15 of which differed between breeds. Yk scars had a higher VSS score at all time points. Yk and Dc wounds had equivalent re‐epithelialization, collagen disorganization, and blood vessel density. Conclusions Our findings demonstrate that Dc and Yk pigs can produce HTS. Wound creation and healing were consistent among breeds, and differences in gene expression were not sufficient to explain differences in resulting scar phenotype. Both pig breeds should be used in animal models to investigate novel therapeutics to provide insight into a treatment's effectiveness on various skin types.

Due to the lack of a delivery system that actively targets hypertrophic scar fibroblasts (HSFs), it is difficult to concentrate the effects of drugs on hypertrophic scars (HSs). We recently discovered that the HSF membrane has a homologous targeting effect and developed an active targeted drug delivery system for the local treatment of HSs. A diphenyl carbonate cross-linked cyclodextrin metal organic framework (CDF) containing more than 26% (w/w) quercetin (QUE) was coated with a HSF membrane (QUE@HSF/CDF) and then dispersed in Bletilla striata polysaccharide (BSP)-fabricated dissolvable microneedles (BSP-MNs-QUE@HSF/CDF) for local administration. This biomimetic nanodrug delivery system improved efficacy on HSs by regulating Wnt/β-catenin and JAK2/STAT3 pathways and reducing the expression of collagens I and III in HS, and this performance was superior to those of systems without HSF functionalization or the assistance of microneedles. Additionally, we found that BSP has synergistic effects and the microneedles have higher mechanical strength and better physical stability than microneedles made of hyaluronic acid. This currently designed drug delivery strategy integrating biomimetic nanoparticles and dissolvable microneedles is promising for applications in the fields of skin disease treatment and cosmetics.

Scars are common complications of burns and trauma, resulting in mental trauma, physical pain, and a heavy financial burden for patients. Specific and effective anti-scarring drugs are lacking in clinical practice. Phytochemicals are easily accessible, low in toxicity, and have various biological and pharmacological properties. Oxymatrine is a phytochemical that regulates autophagy networks. Autophagy is closely related to the maintenance, activity, differentiation, and life-death of skin fibroblasts during wound repair, which results in pathological scars. We hypothesised that oxymatrine may promote hypertrophic scar repair by inhibiting fibroblast autophagy. In vitro studies showed that inhibition of autophagy by oxymatrine decreased viability and collagen metabolism, and increased apoptosis of human scar fibroblasts (HSFs). In vivo studies showed that inhibition of autophagy by oxymatrine promoted scar repair, resulting in a significantly improved final outcome of the hypertrophic scars, a smaller scar area, decreased epidermal and dermal thickness, and a significant downregulation of CK10, P63, collagen I, α-SMA, and TGF-β1. In summary, oxymatrine promoted hypertrophic scar repair by decreasing HSF viability and collagen, and inducing apoptosis via autophagy inhibition. This study provides a new perspective on the mechanism of hypertrophic burn scar formation, as well as key scientific data for the application of the phytochemical oxymatrine as a new method for the prevention and treatment of hypertrophic scars.

OBJECTIVE Scar revision is 1 of the basic surgery in the field of plastic and reconstructive surgery. The classic treatment of the scar is excision scarless tissue, wide undermining and suture by planes. This method has had unsatisfying results on contracted and tethered scars. The aim of this study is to present the three-dimensional subcutaneous z-plasty technique for correction of tethered facial scars without scar lengthening. MATERIALS AND METHODS Twenty tethered scars were corrected using this technique. All scars were located on the face. Objectively, the final result was evaluated by using the Stony Brook Scar Evaluation Scale. Subjectively, patients' overall satisfaction was assessed 1 year after the surgical operation. In addition, the information on the age, gender, etiology, scar location, scar length, type of anesthesia, and follow-up period were examined. RESULTS This procedure was used in nineteen patients (8 males and eleven females). The mean follow-up period was 15.3 months. There was a mean increase of 2.85 points increase in the Stony Brook Scar Evaluation Scale value. The overall success rates for the procedure, as assessed by the patients, were: very satisfied in 12 patients, satisfied in 5 patients, and slightly satisfied in 2 patients. One patient had minimal wound dehiscence. No complications including hypertrophic scar, infection, hematoma, and suture reaction were observed in any patients. CONCLUSIONS The three-dimensional subcutaneous z-plasty technique is a procedure that uses only basic plastic surgery principles. It offers a good solution for the correction of tethered and contracted scars without recurrence. This technique combines the advantages of elliptical excision and z-plasty by enabling the augmentation of the depressed area without extending the scar length.

Background A car-tire friction injury on the dorsum of a child’s foot often results in hypertrophic scarring of the wound margins. This study describes the clinical appearance of the injured areas and surgical complications that occurred during the follow-up period in a series of children with car-tire friction injuries who were treated with split-thickness skin grafts (STSGs). We describe the clinical features that we believe need to be highlighted when initially treating car-tire injuries in children. Methods From May 2003 to June 2016, our retrospective study included 15 patients with car-tire injuries on the dorsum of the foot who were treated with surgical excision and STSG to cover the wound. Results A total of 15 patients with car-tire injuries were treated. The average age was 6.26 years old. The average injury grade was 3.26. Two patients were treated using delayed repair, and 13 patients received STSG for initial management. Four patients experienced no complications, while 11 patients had hypertrophic scars and/or scar contracture after surgery. Conclusions A car-tire friction injury on the dorsum of a child’s foot often results in hypertrophic scar formation or scar contracture even if proper management is undertaken. Since the occurrence of these complications in childhood can lead to a secondary deformity, it is important to properly treat car-tire friction wounds, inform patients and caregivers about potential complications, and ensure regular follow-up evaluations over a 12-month period following the initial surgery.

Summary Background The effect of Botulinum toxin type A (BTX-A) in treating or preventing a hypertrophic scar (HS) had been reported in clinical studies. However, the dose-effect relationship remains unclear. Objective To study the dose-effect relationship of BTX-A intralesional monotherapy treating human HS. Methods Six HS tissues were collected from six patients. Each tissue was segmented into 24 specimens and split into four groups: negative control (group A), 0.5U BTX-A (group B), 1U BTX-A (group C), and 2U BTX-A (group D). Six nude mice, each was prepared by implanting four specimens (one from each group) into the back for a total of 24 specimens. The process mentioned above were repeated six times. A re-entry operation was performed to obtain the specimens after 8 weeks. The weight of HS, the expression of decorin and TGF-β1, the proliferation, and migration ability of hypertrophic scar fibroblasts (HSFBs) were compared among groups. Results The weight of HS, the expression of decorin and TGF-β1, the proliferation, and migration ability of HSFBs showed significant differences in groups C and D as compared to group A; there has been no statistical significance in group B. Conclusion BTX-A showed significant therapeutic efficacy when compared with the negative control group in a dose-dependent manner. BTX-A can reduce the weight of HS, upregulate the expression of decorin, downregulate the expression of TGF-β1, and inhibit HSFBs proliferation and migration ability. This study indicates that BTX-A intralesional monotherapy treating HS should reach a threshold dose to achieve an effective treatment, and a high dose of BTX-A is more effective than a low dose.

The aim of this study is to determine whether Z-plasty combined with fractional CO2 laser therapy can be a potential management option for hypertrophic burn scars in the proliferation stage. A total of 105 patients (46 male and 59 female patients) diagnosed with hypertrophic scars under tension but without any functional limitations were enrolled in this study. The Vancouver Scar Scale (VSS) score and scar height were analyzed and compared. The VSS scores for all scars were improved in all groups after treatment. The scar height was also significantly decreased in each group after treatment (P 12 month time point for the C group, there was a significant difference between the ≦ 6 month time point for the L group and the > 12 month time point for the Z group. The proportion of satisfied patients was highest at 89.47% at the ≦6 month time point in the C group and lowest at 65.52% at the > 12 month time point in the L group. Six representative cases are presented. Z-plasty can decrease the thickness of a hypertrophic burn scar, which not only reduces the scar tension but also makes it easy to treat the scar with a fractional CO2 laser. Subsequent treatment with a fractional CO2 laser can better improve the color and texture of the scar.

Background In 2010, this Journal published my comprehensive review of the literature on hypertrophic scars and keloids. In that article, I presented evidence-based algorithms for the prevention and treatment of these refractory pathologic scars. In the ensuing decade, substantial progress has been made in the field, including many new randomized controlled trials. To reflect this, I have updated my review. Methods All studies were evaluated for methodologic quality. Baseline characteristics of patients were extracted along with the interventions and their outcomes. Systematic reviews, meta-analyses, and comprehensive reviews were included if available. Results Risk factors that promote hypertrophic scar and keloid growth include local factors (tension on the wound/scar), systemic factors (e.g., hypertension), genetic factors (e.g., single-nucleotide polymorphisms), and lifestyle factors. Treatment of hypertrophic scars depends on scar contracture severity: if severe, surgery is the first choice. If not, conservative therapies are indicated. Keloid treatment depends on whether they are small and single or large and multiple. Small and single keloids can be treated radically by surgery with adjuvant therapy (e.g., radiotherapy) or multimodal conservative therapy. For large and multiple keloids, volume- and number-reducing surgery is a choice. Regardless of the treatment(s), patients should be followed up over the long term. Conservative therapies, including gel sheets, tape fixation, topical and injected external agents, oral agents, and makeup therapy, should be administered on a case-by-case basis. Conclusions Randomized controlled trials on pathologic scar management have increased markedly over the past decade. Although these studies suffer from various limitations, they have greatly improved hypertrophic scar and keloid management. Future high-quality trials are likely to improve the current hypertrophic scar and keloid treatment algorithms further.

Revision surgery after gender-affirming genitoplasty is becoming more and more common as more patients gain access to surgical treatment. The complexity of genitoplasty and extensive dissection of delicate tissues predisposes patients to necrosis of the flap(s) employed, which can leave patients with complications ranging from poor aesthetics to total lack of genital sensation. The purpose of this report is to detail the revision surgery of a 32-year-old transgender woman who underwent vaginoplasty at an outside institution and presented to our clinic for clitoral reconstruction following necrosis and near-total loss of the neoclitoris. Physical exam showed extensive necrosis, and 3-Tesla magnetic resonance (MRI) revealed significant scarring of the pudendal nerve branches at the level of the pubic symphysis. Healthy nerve was identified at the level of the right inferior pubic ramus, and total clitoral reconstruction with an innervated first dorsal web space free flap anastamosed to the deep inferior epigastric vessels was performed. Complications included donor site cellulitis with partial loss of the skin graft and formation of hypertrophic scar tissue. This was treated 6 months postoperatively with excision of scar tissue in the webspace and placement of an additional full-thickness skin graft. At follow-up, the patient reported tactile and erogenous sensation of the neoclitoris itself and subjective satisfaction with the aesthetic outcome. Our results provide evidence that this flap is a feasible option to create an aesthetic and sensate neoclitoris in the setting of previous neoclitoral necrosis. This case report also describes the novel use of 3-Tesla MRI in target selection for nerve coaptation.

Introduction Adipose-derived stem cells (ASCs) have recently gained researchers' interest as a solution to various diseases and conditions, including hypertrophic scar. This literature review aims to elucidate ASCs as a potential solution to alleviate hypertrophic scar in human subjects. Methods Literature search was done in databases which includes PubMed, MEDLINE, and ProQuest using terms 'adipose derived stem cells', 'adipose cells', 'fat graft', 'fat grafting', 'autologous fat graft', 'fat injection', 'lipofilling', 'scar management', 'scar treatment', 'burn scar', and 'wound management'. The included articles which were published during year 2000-November 2020 must describe the use of ASCs or fat grafting or lipofilling as an attempt to alleviate hypertrophic scar. Remarks Clinically, ASCs improve hypertrophic scars in terms of scar color, elasticity, texture, thickness, and size. Histologically, ASCs promotes healthy tissue regeneration, reduction in fibroblasts, and reorganisation of collagen, resembling those of normal skin. In terms of molecular aspects, ASCs alleviates hypertrophic scars through direct differentiation and paracrine mechanisms. Conclusion Adipose-derived stem cells, emerge to be a potential solution for alleviating hypertrophic scar, as demonstrated in various studies. However, there has been no studies conducted in human subjects to investigate the effect of ASCs on hypertrophic scar.

Hypertrophic scars are the most common post-burn complications characterized by fibroblast proliferation and excessive extracellular matrix deposition. The intermediate-conductance Ca2+-activated K+ channel (KCa3.1) mediates fibroblast activation, resulting in several fibrotic diseases; however, this channel's role in the formation of post-burn hypertrophic skin scars remains unknown. Herein, we investigated the role of KCa3.1 and the therapeutic potential of TRAM-34, a selective inhibitor of KCa3.1, in hypertrophic skin scar formation following burn injury. Cytosolic Ca2+ levels, the expression of KCa3.1 and hypertrophic markers, and the proliferation of skin fibroblasts obtained directly from patients with third-degree burns who consequently developed post-burn hypertrophic scars were assessed. The anti-fibrotic effect of KCa3.1 inhibition by TRAM-34 was evaluated in vitro (fibroblasts) and in vivo (mouse burn models). Fibroblasts from burn wounds exhibited remarkably higher levels of cytosolic Ca2+ than normal cells. KCa3.1 expression was markedly higher in the membrane fraction but lower in the cytosolic fraction of burn wound fibroblasts than in normal cells. Selective inhibition of KCa3.1 by TRAM-34 markedly reduced not only the proliferation of burn wound fibroblasts but also the expression of hypertrophic markers in these cells. Anti-scarring molecular, histological, and visual effects of TRAM-34 were confirmed in murine burn models. Altered subcellular expression of KCa3.1 is a novel mechanism underlying the cellular response to burn injury. Our results suggest that selective inhibition of KCa3.1 by TRAM-34 has therapeutic potential against post-burn hypertrophic scar formation.

Despite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study, we investigate mature human hypertrophic scars and developing scars in mice at single cell resolution. Compared to normal skin, we find significant differences in gene expression in most cell types present in scar tissue. Fibroblasts show the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine fibroblasts during scar development with genes highly expressed in mature human hypertrophic scars, we identify a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), are further analyzed in functional assays, revealing a role in TGFβ1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix in vitro. Topical treatment with inhibitors of DPP4 and PLAU during scar formation in vivo shows anti-fibrotic activity and improvement of scar quality, most prominently after application of the PLAU inhibitor BC-11. In this study, we delineate the genetic landscape of hypertrophic scars and present insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis., Mechanisms triggering hypertrophic scar formation remain poorly understood. Here the authors perform scRNA-seq on mature human hypertrophic scars and developing scars in mice to identify the serine proteases dipeptidyl-peptidase 4 and urokinase as key molecules in this process.

Background: Keloids and hypertrophic scars are dermal fibro-proliferative disorders lead to disfigurement, pain and pruritus. Their management is still challenging as there is no universally accepted treatment regimen. Corticosteroid injections, most commonly triamcinolone acetonide, continue to play a major role in the management of keloids. Verapamil is a phenylalkylamine calcium channel blocker antiarrhythmic agent that has antifibrotic effect. Objective: To compare efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids. Patients and methods: Forty Egyptian patients with keloids or hypertrophic scars were divided into two equal groups. The patients were recruited from the Dermatology outpatient clinics of Al-Zahraa University Hospital during the period from May 2016 to May 2017. Informed written consents were obtained from all patients. Group A: Intralesional Verapamil Hydrochloride. Group B: Intralesional Triamcinolone Acetonide. The efficacy of treatment was evaluated by Digital photography and Vancouver scar scale before and after treatment. Two- fine millimeter punch biopsies were taken from 5 patients of the verapamil group before and after treatment to demonstrate the histopathological changes induced by verapamil. Results: Both drugs improved total Vancouver scar scale, vascularity score and pliability score of keloid or hypertrophic scar nearly equally with no statistical significant difference. Both drugs improved height of keloid or hypertrophic scar significantly, but triamcinolone showed better improvement. Verapamil highly improved pigmentation score of keloids and hypertrophic scars, but triamcinolone showed non- significant improvement. Side effects were reported in 4 patients of triamcinolone group with no side effects in verapamil group. The histopathological examination after treatment with verapamil injection showed marked reduction of collagen deposition and alteration of the fibroblast shape (from elongated to spherical), and these changes are similar to histopathological changes which occur after corticosteroids injection. Conclusion: Verapamil was among the several therapeutic modalities, have an option for keloids and hypertrophic scars with an extremely low cost and fewer adverse effects.

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin-2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin-2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin-2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha-smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin-2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin-2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin-2 might be a potential target to treat the HTS.

Background: Hypertrophic scar is a fibroproliferative disorder caused by skin injury. The incidence of hypertrophic scar following trauma or burns is 40 to 70 percent or 70 percent, respectively. It has been shown that transforming growth factor (TGF) β1/Smad signaling plays a crucial role in hypertrophic scar, and that USP15 can regulate the activity of TGFβ1/Smad signaling to affect the progression of the disease. However, the underlying mechanism of USP15 in hypertrophic scar remains unclear. The authors hypothesized that USP15 was up-regulated and enhanced the proliferation, migration, invasion, and collagen deposition of hypertrophic scar–derived fibroblasts by deubiquitinating TGF-β receptor I (TβRI) in vitro. Methods: Fibroblasts were isolated from human hypertrophic scars in vitro. The knockdown and overexpression of USP15 in hypertrophic scar–derived fibroblasts were performed using lentivirus infection. The effect of USP15 on hypertrophic scar–derived fibroblast proliferation, migration, and invasion, and the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3, were detected by Cell Counting Kit-8, scratch, invasion, quantitative real-time polymerase chain reaction, and Western blot assays. The interaction between USP15 and TβRI was detected by co-immunoprecipitation and ubiquitination assays. Results: The authors demonstrated that USP15 knockdown significantly inhibited the proliferation, migration, and invasion of hypertrophic scar–derived fibroblasts in vitro and down-regulated the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3; in addition, USP15 overexpression showed the opposite trends (p < 0.05). Co-immunoprecipitation and ubiquitination assays revealed that USP15 interacted with TβRI and deubiquitinated TβRI. Conclusion: USP15 enhances the proliferation, migration, invasion, and collagen deposition of hypertrophic scar–derived fibroblasts by deubiquitinating TβRI in vitro.

BACKGROUND Various laser therapies have been introduced in scar management. However, pain during treatment has limited the application of laser therapy in pediatrics. OBJECTIVES To evaluate whether the use of the low-energy mode of a carbon dioxide (CO2 ) laser improves hypertrophic scars in a pediatric population. METHODS This prospective, randomized, split-scar trial was designed to assess the safety and efficacy of low-energy CO2 laser use. Patients aged

Background: Hypertrophic scar is an abnormal scar that causes physical deteriorations, psychological problems, and aesthetic issues. An excessive number of fibroblasts and collagen III expressions are histopathology indicators for the hypertrophic scar. The role of topical corticosteroids in suppressing inflammation and hypergranulation had widely demonstrated in previous studies. However, there is no study related to the application of topical corticosteroids as prevention of hypertrophic scars from burn wound found. Hence, this study aimed to examine the evidence of the effects of corticosteroid topical in decreasing the number of fibroblasts and type III collagen expression and the best time to start its application in preventing hypertrophic scars. Methods: This randomized experimental post-test only study involved 54 deep dermal burn wounds on the ventral ear of female Oryctolagus cuniculus that distributed into three groups based on the healing phases. Each group consisted of treatments and controls. Corticosteroid topical application on the first treatment group (inflammatory phase group), the second group (proliferation phase group), and the third group (remodelling phase group) was started on day 3, on day 10, and day 21, respectively. Specimens taken on day 35. Haematoxylin-Eosin and Immunohistochemically staining performed to measure the number of fibroblasts and type III collagen and to observe the epithelization and inflammation process. Results: The number of fibroblasts significantly decreased in the second treatment group (p =0.001) and followed by the first group (p = 0.016), but no significant decrease found in the third group (p = 0.430). The type III collagen decreased significantly in the second treatment group (p = 0.000) and followed by the third group (p = 0.019), but no significant decrease found in the first group. There was no statistically different number of fibroblast and type III collagen discovered between the controls. Complete epithelization found in all groups. Also, no ongoing inflammation found in all groups. Conclusion : Topical corticosteroids on deep dermal burn wound revealed to be effective in reducing the number of fibroblasts and type III collagen with no healing disruption. The proliferation phase found to be the best time to start the application of topical corticosteroids.

Background. Hypertrophic scar (HS) is a benign fibroproliferative skin disease resulting from an aberrant wound healing process and can cause aesthetic and functional damage to patients. Currently, there is no ideal treatment to treat this disease. Galangin, a natural active bioflavonoid compound, is suggested to inhibit fibrosis and proliferation in certain cells. Methods. In this study, we found Galangin could attenuate abnormal scar formation in an HS rabbit ear model. Additionally, the HE staining shows Galangin reduced scar elevation index (SEI) and Masson’s trichrome staining changed collagen deposition. Results. The expressions of type I collagen, type III collagen, and TGF-β1 were much lower under a proper dose of Galangin treatment, and Smad7 expression was also enhanced, which are examined by real-time PCR, immunohistochemistry, and western blot. Conclusion. Our data indicated that Galangin can alleviate dermal scarring via the TGF-β/Smad signaling pathway probably by upregulating Smad 7 expression and, thus, suppressing the expression of type I and type III collagens and TGF-β1.

TGF-β1 (transforming growth factor β1) was considered to play a critical role in the forming of hypertrophic scars. Smad, as a kind of signal downstream mediators, can modulate the functions of TGF-β1. Smad7 can regulate TGF-β1/Smad pathway and present negative feedbacks, which prevents fibrosis mediated by TGF-β1. Nonetheless, the mechanisms related to Smad7 activity in regulating hypertrophic scarring are hardly known. The studies have shown that Smad7 decrease induced by the increase of Smurf2 (Smad ubiquitination regulatory factor 2, an E3 ubiquitin ligase of Smad7) ubiquitination degradation plays a part in fibrosis. We thus made a hypothesis that Smad7 could not inhibit TGF-β1 because Smurf2 ubiquitin degradation was increased in hypertrophic scar fibroblasts. In our research, it was discovered that there was an increase in Smad7 mRNA levels but no increase in Smad7 protein levels in the fibroblasts of hypertrophic scars after TGF-β1 treatment. The ubiquitination activity and degradation of Smad7 protein were increased in the fibroblasts of hypertrophic scars compared with the fibroblasts of normal skin. Enhanced degradation of Smad7 protein in the fibroblasts of hypertrophic scars was prevented by proteasome inhibitors MG132 / MG115. Furthermore, it was found that TGF-β1 stimulation increased Smad7 protein expression after silencing Smurf2 gene in hypertrophic scar fibroblasts, and enhanced Smad7 degradation was prevented in hypertrophic scar fibroblasts after Smurf2 was silenced. It was implied that ubiquitin degradation mediated by Smurf2 might contribute to decreased Smad7 protein levels following TGF-β1 stimulation in the fibroblasts of hypertrophic scars.

Background Hypertrophic scars can be caused by various injuries and lead to a decrease in quality of life of those affected. This study was performed retrospectively in our center to investigate the safety and effectiveness of fractional micro-plasma radio-frequency treatment combined with ablative fractional carbon dioxide (CO2) laser treatment in patients with hypertrophic scar. Methods This was a retrospective study performed in a single center between January 2019 and December 2020. All patients with hypertrophic scars receiving fractional micro-plasma radio-frequency treatment, ablative fractional CO2 laser treatment, or combined therapy of both were recruited to the study. The participants were then divided into a single therapy group or combined therapy group. The Vancouver scar scale was used to score and subsequently assess the effectiveness of scar treatment and the changes of scar thickness. Some adverse complications were also recorded to evaluate the safety of treatments. A subgroup analysis was then performed to investigate the differences of effectiveness and safety of combined therapy in scar patients at the early stage and late stage. Results A total of 64 patients with hypertrophic scars were enrolled in this study, including 45 receiving combined treatment, and 19 receiving single treatment. There was no significant difference in demographic data between the two groups. Notably, combined therapy could more effectively reduce the score of Vancouver scar scale (P=0.026) without significantly increasing the incidence of adverse complications. However, no significant difference was observed in scar thickness between the two groups. Moreover, multiple treatments could further increase the effectiveness of combined therapy according to either the score of Vancouver scar scale or the thickness of scars. Subgroup analysis revealed that combined therapy could reduce the score of Vancouver scar scale and scar thickness in patients much more at the early stage than at the late stage (P=0.032 and 0.042, respectively). Conclusions This study revealed that fractional micro-plasma radio-frequency treatment combined with ablative fractional CO2 laser treatment could be more effective in improving hypertrophic scars then single therapy. Also, multiple treatments could enhance the effectiveness of combined treatment, and patients should be encouraged to receive treatment as early as possible.

Background Hypertrophic scars are devastating outcomes of severe burn injuries, producing physical and mental burdens. Adequate treatment is of benefit to relieve these burdens. Laser therapy has shown scar reducing effects. In this study, we compared outcomes after combination of two different lasers or single laser treatment to treat severe hypertrophic burn scars. Methods Forty patients with hypertrophic burn scars were included in one of two therapeutic groups: continuous wave CO2 laser and fractional ablative CO2 laser group (group 1, n = 20) or fractional ablative CO2 laser alone group (group 2, n = 20). Hypertrophic scars were evaluated by the observer-rated Vancouver Scar Scale (VSS) before and after treatment and by patient-completed questionnaires after treatment. Comparative analyses were performed before and after treatment, and time-dependent improvement was also analyzed. Results Forty patients (54 hypertrophic scars) completed the laser treatment protocols. Group 1 exhibited significantly more improvement in VSS vascularity, pliability, and height indices than group 2 (p Conclusion Effective scar reduction was achieved using combination laser treatment, with significant improvement in multiple observer- and patient-reported outcomes. The shorter treatment period of the combination method can be a merit, as prolonged hypertrophic scars may increase morbidity. Nonetheless, cautious treatment protocols are necessary to avoid undesirable sequelae related to laser application.

Background Lipofilling has become popular as a treatment to improve aging-related skin characteristics (eg, wrinkles, pigmentation spots, pores, or rosacea). Different additives such as platelet-rich plasma (PRP) or stromal vascular fraction (SVF) have been combined with lipofilling to increase the therapeutic effect of adipose-derived stromal cells (ASCs). Objectives The aim of this study was to examine the hypothesis that mechanically isolated SVF augments the therapeutic effect of PRP-supplemented lipofilling to improve facial skin quality. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2019. In total, 28 female subjects were enrolled; 25 completed the follow-up. All patients received PRP-supplemented lipofilling with either mechanically isolated SVF or saline. SVF was isolated by fractionation of adipose tissue (tSVF). Results were evaluated by changes in skin elasticity and transepidermal water loss, changes in skin-aging-related features, ie, superficial spots, wrinkles, skin texture, pores, vascularity, and pigmentation, as well as patient satisfaction (FACE-Q), recovery, and number of complications up to 1 year postoperative. Results The addition of tSVF to PRP-supplemented lipofilling did not improve skin elasticity, transepidermal water loss, or skin-aging-related features. No improvement in patient satisfaction with overall facial appearance or facial skin quality was seen when tSVF was added to PRP-supplemented lipofilling. Conclusions In comparison to PRP-supplemented lipofilling, PRP-supplemented lipofilling combined with tSVF does not improve facial skin quality or patient satisfaction in a healthy population. PRP-supplemented lipofilling combined with tSVF can be considered a safe procedure. Level of Evidence: 2

Very few objective scar evaluations have been conducted with burn survivors, which limits our knowledge of the clinical recovery profile of hypertrophic scars (HSc) and donor site scars (D). The purpose of this study was to prospectively quantify the skin characteristics of post-burn HSc in different anatomical locations (D) and normal skin (N) using objective instrumentation. The skin characteristics of HSc, D, and N in 44 burn survivors were measured at 2, 3, 4, 5, 6, and 7 months post-burn using validated instrumentation: a high-frequency ultrasound (for thickness), Cutometer® (for pliability), and Mexameter® (for erythema and pigmentation). Up to five sites were assessed on the same participant, if their scar was located on the upper extremity (UE), lower extremity (LE), and trunk. A mixed model two-way analysis of variance was used to investigate the differences in means between sites at each time point and between time points at each site. The results revealed that the HSc sites were thicker than the D and N at all time points, the UE and trunk HSc were thicker than the LE HSc at 7 months post-burn, the pliability of the trunk HSc did not improve over time, and the UE HSc was more erythematous at 7 months, compared to other anatomical sites, whereas the D erythema decreased from 2 to 7 months. As clinicians have prioritized UE treatments due to their functional importance, this study provides objective measurements to further support this practice and encourages clinicians to also prioritize trunk HSc treatments after burn injuries.

Objective To study the clinical efficacy, recurrence rate and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with microneedle or CO2 lattice laser (CO2FL), in comparison with intrascar betamethasone injection in the treatment of hypertrophic acne scar. Methods Fifty-two patients with hypertrophic acne scars at the mandibular angle were enrolled and assigned to different therapy groups. Sixteen patients were treated with microneedle-assisted incorporation of ALA. Twenty-eight patients underwent CO2FL-assisted incorporation of ALA. Eight patients received standard therapy with intrascar injection of glucocorticoid. Two dermatologists, blinded to the therapy groups, independently evaluated the scars in all patients using the average value of the Vancouver Scar Scale score, which was treated as an integer variable. Results After three rounds of treatment, there was no significant difference in therapeutic effective rate among the microneedle, laser and topical glucocorticoid groups (93.75% vs 100% vs 100%, P = .855). One out of 16 patients (6.25%) in the microneedle group, no patient (0%) in the laser group and two out of eight patients (25%) in the topical glucocorticoid group had recurrence. The laser group showed a higher rate of adverse effects, which were usually mild and reversible, except for pigmentation. Adverse reactions could be completely subsided within 3 weeks. Conclusions Either CO2FL or microneedle combined ALA-PDT for hypertrophic scar, as to topical glucocorticoid therapy, showed equivalent clinical effects but lower recurrence rate within 6 months of follow-up period.

Hypertrophic scars and keloids are caused by excessive tissue response to dermal injury due to local fibroblast proliferation and collagen overproduction. This response occurs because of pathologic wound healing due to dysregulation in the inflammatory, proliferative, and/or remodeling phase. Patients with hypertrophic scars or keloids report reduced quality of life, physical status, and psychological health. Hypertrophic scars or keloids will develop in 30 to 90% of individuals, and despite their prevalence, treatment remains a challenge. Of the treatments currently available for hypertrophic scars and keloids few have been adequately supported by studies with appropriate experimental design. Here, we aim to review the available literature to provide up-to-date information on the etiology, epidemiology, histology, pathophysiology, prevention, and management options available for the treatment of hypertrophic scars and keloids and highlight areas where further research is required.