Search

Background: The skin is a protective barrier of the body against external factors, and its damage leads to a loss of integrity. Normal wound healing results in a correct, flat, bright, and flexible scar. Initial skin damage and patient specific factors in wound healing contribute that many of these scars may progress into widespread or pathologic hypertrophic and keloid scars. The changes in cosmetic appearance, continuing pain, and loss of movement due to contracture or adhesion and persistent pruritis can significantly affect an individual's quality of life and psychological recovery post injury. Many different treatment methods can reduce the trauma and surgical scars. Manual scar treatment includes various techniques of therapy. The most effectiveness is a combined therapy, which has a multidirectional impact. Clinical observations show an effectiveness of manual scar therapy., Material and Methods: The aim of this work was to evaluate effectiveness of the scar manual therapy combined with complementary methods on the postoperative scars. Treatment protocol included two therapies during 30 min per week for 8 weeks. Therapy included manual scar manipulation, massage, cupping, dry needling, and taping., Results: Treatment had a significant positive effect to influence pain, pigmentation, pliability, pruritus, surface area, and scar stiffness. Improvement of skin parameters (scar elasticity, thickness, regularity, color) was also noticed., Conclusion: To investigate the most effective manual therapy strategy, further studies are needed, evaluating comparisons of different individual and combined scar therapy modalities., (© 2022 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Introduction: Hypertrophic scars are a common disease in plastic surgery, which is the reaction of skin connective tissue to trauma beyond the normal range. Although scholars around the world have explored the tissue structure and formation mechanism of HS for decades, they are not satisfactory the result of. No effective treatment has been found. Therefore, the search for safe and effective treatments for HS has always been the focus of medical attention and research. Acupuncture therapy has a definite effect on HS and has unique advantages., Methods/design: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for HS. The untreated HS of the enrolled patients will be used as blank controls. The intervention group will be given acupuncture treatment. The assessment of scar area, color, hardness, thickness, itching and pain will be recorded for 30 days of treatment., Discussion: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Acupuncture for patients with HS., Trial Registration: ClinicalTrials.gov, ChiCTR2000032624, Registered on 04 May 2020.

Matrix deposition is essential for wound repair, but when excessive, leads to hypertrophic scars and fibrosis. The factors that control matrix deposition in skin wounds have only partially been identified and the consequences of matrix alterations for the mechanical properties of wounds are largely unknown. Here, we report how a single diffusible factor, activin A, affects the healing process across scales. Bioinformatics analysis of wound fibroblast transcriptome data combined with biochemical and histopathological analyses of wounds and functional in vitro studies identify that activin promotes pro-fibrotic gene expression signatures and processes, including glycoprotein and proteoglycan biosynthesis, collagen deposition, and altered collagen cross-linking. As a consequence, activin strongly reduces the wound and scar deformability, as identified by a non-invasive in vivo method for biomechanical analysis. These results provide mechanistic insight into the roles of activin in wound repair and fibrosis and identify the functional consequences of alterations in the wound matrisome at the biomechanical level.

Hypertrophic scarring (HSc) is an age-old problem that still affects millions of people physically, psychologically, and economically. Despite advances in surgical techniques and wound care, prevention and treatment of HSc remains a challenge. Elucidation of factors involved in the development of this common fibroproliferative disorder is crucial for further progress in preventive and/or therapeutic measures. Our knowledge about pathophysiology of HSc at the cellular and molecular level has grown considerably in recent decades. In this article, current knowledge of predisposing factors and the cellular and molecular mechanisms of HSc has been reviewed., (© American Burn Association 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Research into the treatment of hypertrophic burn scar is hampered by the variability and subjectivity of existing outcome measures. This study aims to measure the inter- and intra-rater reliability of a panel of subjective and objective burn scar measurement tools., Methods: Three independent assessors evaluated 55 scar and normal skin sites using subjective (modified Vancouver Scar Scale [mVSS] & Patient and Observer Scar Assessment Scale [POSAS]) and objective tools. The intra-class correlation coefficient was utilised to measure reliability (acceptable when >0.70). Patient satisfaction with the different tools and scar parameter importance were assessed via questionnaires., Results: The inter-rater reliabilities of the mVSS and POSAS were below the acceptable limit. For erythema and pigmentation, all of the Scanoskin and DSM II measures (except the b* value) had acceptable to excellent intra and inter-rater reliability. The Dermascan ultrasound (dermal thickness, intensity) had excellent intra- and inter-rater reliability (>0.90). The Cutometer R0 (firmness) had acceptable reliability but not R2 (gross elasticity). All objective measurement tools had good overall satisfaction scores. Patients rated scar related pain and itch as more important compared to appearance although this finding was not sustained when corrected for multiple comparisons., Conclusion: The objective scar measures demonstrated acceptable to excellent intra- and inter-rater reliability and performed better than the subjective scar scales., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This cross-sectional study aimed to investigate whether adipose tissue loss and reduced vitamin D levels following severe burn injury are associated with pathologic scar formation and biomechanical scar properties., Methods: A total of 492 male subjects with hypertrophic burn scars were enrolled from January 2014 to July 2018 and analyzed. Body fat content was measured using dual-energy X-ray absorptiometry. Values of melanin, erythema, and trans-epidermal water loss (TEWL) and the distensibility and elasticity of hypertrophic scars were examined using pigment- and TEWL-measuring devices and a suction skin elasticity meter., Results: Burn patients with higher fat percentage tended to have higher 25(OH) vitamin D levels (P < 0.001). As body fat percentage increased, hypertrophic scars showed higher mean value of Uf (distensibility, P < 0.001) and lower mean value of Uv/Ue (viscoelasticity or interstitial fluid shifting, P < 0.001). Burn patients with higher 25(OH) vitamin D levels tended to have higher mean values of Uf (P < 0.001) and Ua/Uf (gross elasticity, P = 0.013) and lower mean value of Uv/Ue (P = 0.008)., Conclusion: Adipose tissue loss and decreased 25(OH) vitamin D levels following burn injury were related to scar rigidity and slow interstitial fluid shifting in hypertrophic scars., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Hypertrophic scars are dermal fibrosis diseases that protrude from the surface of the skin and irregularly extend to the periphery, seriously affecting the appearance and limb function of the patient. In this study, we found that microRNA-130a (miR-130a) was increased in hypertrophic scar tissues and derived primary fibroblasts, accompanied by up-regulation of collagen1/3 and α-SMA. Inhibition of miR-130a in hypertrophic scars fibroblasts suppressed the expression of collagen1/3 and α-SMA as well as the cell proliferation. Bioinformatics analysis combined with luciferase reporter gene assay results indicated that CYLD was a target gene of miR-130a, and the miR-130a mimic could reduce the level of CYLD. In contrast to miR-130a, the expression of CYLD was downregulated in hypertrophic scars and their derived fibroblasts. Overexpressing CYLD inhibited the expression of collagen 1/3 and α-SMA, slowed cell proliferation, and inhibited Akt activity. As expected, further study showed that the overexpression of CYLD could prevent the pro-fibroproliferative effects of miR-130a. Consistent with the in vitro results, the inhibitor of miR-130a effectively ameliorated excessive collagen deposition in bleomycin-induced skin fibrosis mouse model. Taken together, our results indicate that miR-130a promotes collagen secretion, myofibroblast transformation and cell proliferation by targeting CYLD and enhancing Akt activity. Therefore, the miR-130a/CYLD/Akt pathway may serve as a novel entry point for future skin fibrosis research., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Graft fixation is critical for the successful survival of a skin graft. Conventional mechanical fixation may induce inappropriate pressure and increase wound complications. Negative pressure wound therapy (NPWT) could be utilized to secure a skin graft and improve drainage. Limited quantitative data exist on the efficacy of NPWT for skin grafting., Objective: This retrospective study compares the efficacy and complications between NPWT and conventional mechanical fixation in skin grafts., Materials and Methods: Patients who underwent skin graft surgery from January 2015 to December 2016 at a large university hospital in southwest China were retrospectively analyzed. Characteristics, including wound pattern, skin graft type, surgical procedure, survival rate, and postoperative complication, were statistically analyzed by Pearson chi-square or Fisher's exact test., Results: A total of 186 patients were included in the study; 72 received NPWT and 114 received conventional mechanical dressing fixation after skin grafting. Overall survival rate of full-thickness skin grafts was significantly higher in the NPWT group than the dressing group (P ⟨ .01). The NPWT group showed a higher survival rate than the dressing group for each anatomic site, but only patients who had skin grafts of the hand exhibited statistically significant results., Conclusions: This study reports a quantitative analysis of the efficacy of NPWT on skin graft fixation with NPWT providing consistent pressure and better drainage than conventional mechanical fixation. In addition, the use of NPWT also could increase graft take on the hand region.

Introduction: Cardiothoracic surgery with a median sternotomy is an electing factor for the development of a hypertrophic scar. Hypertrophic scars, characterized by an increased vascularity, often result in aesthetic and functional problems. Smoking, due to its negative effects on vascularization, could therefore have an effect on scar healing., Objective: A prospective cohort study was conducted to evaluate the effect of smoking on scar healing after cardiothoracic surgery with a median sternotomy incision., Materials and Methods: One hundred patients who underwent cardiac surgery with a median sternotomy were divided into 3 groups: smokers, ex-smokers, and nonsmokers. Erythema values of the scar were measured with a colorimeter on 3 standardized parts of the scar. Scar evaluation was performed at 6 weeks, 3 months, 6 months, and 12 months after surgery., Results: During 1 year, a total of 90 patients were followed after a median sternotomy; 10 patients were lost to follow-up. There were 23 smokers, 52 ex-smokers, and 15 nonsmokers with an overall mean age of 61.5 ± 8.83 years. No significant difference in redness as a parameter for hypertrophic scarring was observed between the 3 groups. Nevertheless, a trend in favor of the smokers was seen, as they developed less hyperemic scars. The caudal part of the scar showed a significantly higher incidence of hypertrophy compared with the middle and cranial part of the scar at all time points., Conclusions: It is presumed that a large sample size with younger patients is needed to confirm the results herein. Furthermore, more caudally located skin, especially the subxiphoidal part, is prone to hypertrophic scarring and should, for that reason, be avoided in the incision.

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium ® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

The pathogenesis of hypertrophic scar (HS) is still poorly understood. Macrophages, especially the polarisation of that to M1 or M2, play a pivotal role in control of the degree of scar formation. Profiling of macrophage phenotypes in human specimens during long-term period of wound healing and HS formation may provide valuable clinical evidence for understanding the pathology of human scars. Human wound and HS specimens were collected, the macrophage phenotype was identified by immunofluorescence, and biomarkers and cytokines associated with M1 and M2 macrophages were detected by RT-PCR. The correlation between the macrophage phenotype and HS characteristics was analysed by linear regression analyses. We found excessive and persistent infiltration by M1 macrophages around the blood vessels in the superficial layer of the dermis at early wound tissues, whereas M2 macrophages predominated in later wound tissues and the proliferative phase of HS and were scattered throughout the dermis. The density of M1 macrophages was positively correlated with mRNA expression levels of tumour necrosis factor-alpha (TNF-α) and IL-6. The density of M2 macrophages was positively correlated with ARG1 and negatively correlated with the duration of HS. The sequential infiltration by M1 macrophage and M2 macrophages in human wound and HS tissues was confirmed., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Introduction: Postburn scarring is common, but the risk factors, natural history, and consequences of such scars are still poorly understood. This study aims to describe the frequency of scar-related morbidity for up to 2 years after injury and to analyze the impact of burn scars on long-term functional, psychosocial, and reintegration outcomes., Methods: Analysis was conducted on data collected between January 2006 and May 2014 from 960 patients (2440 anatomic burn sites) using the Burn Model System (BMS) database. Study population demographics were analyzed and odds ratios for the development of raised or thick scarring were determined. Regression analyses were used to evaluate the impact of hypertrophic scarring (HTS) on psychosocial outcomes, including the Community Integration Questionnaire, Satisfaction with Life Scale, Distress, and the Short Form 12. Symptoms associated with scarring were analyzed at discharge and 6, 12, and 24 months after burn using a set of questions on scarring developed by the BMS. Mixed-effect modeling was used to determine linear change over time and the significance of symptoms., Results: The study population was primarily white (65.0%) and male (71.8%), with a mean (SD) age of 44.0 (15.2) years and mean total body surface area burned of 19.6% (17.9%). The incidence of raised or thick scars increased from 65% to 80% (P < 0.0001) for the 2-year follow-up period. The presence of scarring was not associated with Community Integration Questionnaire, Satisfaction with Life Scale, or Short Form 12 scores. Most patients reported symptoms associated with scarring at 2 years after burn, including dry or fragile skin, scars that restrict range of motion at a joint, issues with hand function, and scar pain and itch., Conclusions: In this large, longitudinal, multicenter cohort of burn survivors, nearly all patients noted the presence of scarring, and a majority noted additional symptoms and morbidity related to their scars even at 2 years after injury. This study demonstrates a need for the continued support of burn survivors to address scar-related morbidity. Furthermore, future studies examining the impact of novel treatments for scarring should use similar scar problem questionnaires and distress scores.

Background: There is limited evidence to suggest patients with epidermolysis bullosa (EB) have more postoperative wound complications than the general population. Despite this, the authors have noted reluctance among some surgeons to operate on these patients., Objective: A cross-sectional study was designed to investigate postoperative wound and scar healing outcomes in patients with EB., Methods: Patients were asked to complete the "Surgical Wound and Scar Healing in EB" questionnaire, and data gathered were analyzed., Results: Forty-six patients completed the questionnaire for a total of 94 different surgical procedures. Five patients reported blistering at the surgical wound site. All 5 had generalized forms of EB. Four patients reported wound infections, and 1 patient reported wound dehiscence. The postoperative scar healed with keloid or hypertrophic scarring after 26% of the reported surgical procedures., Conclusion: Blistering at the postoperative site seems to be uncommon and particularly unlikely to occur in localized forms of EB. Postoperative wound infections and dehiscence are uncommon. Patients with EB may have a propensity to develop keloid or hypertrophic scarring. With these data, the authors hope clinicians have greater confidence in referring patients with EB for surgery, and surgeons more reassured about postoperative wound healing.

Background: One objective of massage therapy applied to hypertrophic scar (HSc), is to improve the structural properties so skin possesses the strength and elasticity required for normal mobility. However, research supporting this effect is lacking. The objective of this study was to characterize the changes in scar elasticity, erythema, melanin, and thickness immediately after a massage therapy session and after a 12-week course of treatment compared to intra-individual matched control scars., Methods: We conducted a prospective, randomized, single-blinded, pragmatic, controlled, clinical trial evaluating the impact of a 12-week course of massage therapy. Seventy burn survivors consented to participate and 60 completed the study. Two homogeneous, intra-individual scars were randomized to usual care control or massage therapy plus usual care. Massage, occupational or physical therapists provided massage treatment 3x/week for 12 weeks. Scar site characteristics were evaluated weekly immediately before and after massage treatment including elasticity (Cutometer), erythema and melanin (Mexameter), and thickness (high-frequency ultrasound). Analysis of covariance (ANCOVAs) were performed to test for immediate and long-term treatment effects. A mixed-model approach was used to account for the intra-individual scars., Results: Scar evaluation immediately before and after massage therapy at each time point revealed changes for all scar characteristics, but the group differences were predominantly present during the early weeks of treatment. The within group long-term analysis revealed a significant increase in elasticity, and a reduction in thickness, during the 12-week treatment period for both the control scar (CS) and massage scar (MS). The increase in elasticity reached significance at week 8 for the MS and week 10 for the CS and the reduction in thickness at week 5 for the CS and week 7 for the MS. There was no significant within group long-term differences for either erythema or melanin. There were group differences in erythema at week 8 and 11 where the CS was less erythematous than the MS., Conclusions: The immediate impact of forces applied during massage therapy may lead patients and therapists to believe that there are long-term changes in elasticity, erythema, and pigmentation, however, once baseline measures, the control scar, and time were incorporated in the analysis there was no evidence of long-term benefit. Massage therapy applied with the objective of increasing scar elasticity or reducing erythema or thickness over the long-term should be reconsidered., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

The aim of this study was to compare the quality of postburn facial scars before and after injection of unfiltered nanofat. The study was performed in the Plastic Surgery Department of Mayo Hospital, Lahore, Pakistan, from January 2015 to December 2016. Forty-eight patients with postburn facial scars were included; age range was 4 to 32 years with Fitzpatrick skin types between 3 and 4. Patients with hypertrophic scars, contractures, or keloids were excluded. Scars were assessed by a senior plastic surgeon and the patient on the POSAS (Patient Observer Scar Assessment Scale). Fat was harvested from the abdomen and/or thighs with a 3-mm multiport liposuction cannula (containing several sharp side holes of 1 mm) using Coleman technique. The harvested fat was emulsified and transferred into 1-mL Luer-Lock syringes for injection into the subdermal or intradermal plane. Final follow-up was scheduled at 6 months, and scar was rated by the patient and the same surgeon on the POSAS. Preoperative and postoperative scar scores were compared, and P values were calculated. Results indicated that after nanofat grafting, there was a statistically significant improvement in scar quality. The most significant improvements on the observer scale were seen in pigmentation and pliability (P < 0.0001). Thickness and relief were the least improved variables (P = of 0.785 and 0.99, respectively). ImageJ scanning also showed pigmentation change (P = 0.076). A statistically significant improvement was seen in all parameters of the patient section of the POSAS (P < 0.0001). In conclusion, unfiltered nanofat grafting seems to be a promising and effective therapeutic approach in postburn facial scars, showing significant improvement in scar quality. The trial was registered on www.clinicaltrials.gov with following ID NCT03352297.

Hypertrophic scar (HTS) occurs frequently after burn injury. Treatments for some aspects of scar morbidity exist, however, dyspigmentation treatments are lacking due to limited knowledge about why scars display dyschromic phenotypes. Full thickness wounds were created on duroc pigs that healed to form dyschromic HTS. HTS biopsies and primary cell cultures were then used to study pigmentation signaling. Biopsies of areas of both pigment types were taken for analysis. At the end of the experiment, melanocyte-keratinocyte cocultures were established from areas of differential pigmentation. Heterogeneously dyspigmented scars formed with regions of hyperpigmentation and hypopigmentation. Melanocytes were present in both pigment types measured by S100β quantitative real time-polymerase chain reaction (qRT-PCR) and immunostaining, and visualized by dendritic cell presence in primary cultures. P53 expression was not different between the two pigment types. Hyperpigmented scars had upregulated levels of proopiomelanocortin (POMC), adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), stem cell factor (SCF), and c-KIT and melanocortin 1 receptors (MC1R) compared to hypopigmented regions. Many genes involved in dyspigmentation were differentially regulated by microarray analysis including MITF, TYR, TYRP1, and DCT. MiTF expression was not different upon further exploration, but TYR, TYRP1, and DCT were upregulated in intact biopsies measured by qRT-PCR and confirmed by immunostaining. This is the first work to confirm the presence of melanocytes in hypopigmented scar using qRT-PCR and primary cell culture. An understanding of the initial steps in dyspigmentation signaling, as well as the downstream effects of these signals, will inform treatment options for patients with scars and provide insight to where pharmacotherapy may be directed.

Introduction: The value of compression studies and applications in hypertrophic scar (HTS) treatment is often undermined due to the lack of ideal controls, patient compliance, and clear action mechanisms., Objective: This study assesses the genome-wide compression effects on scars under well-controlled conditions., Materials and Methods: An automated pressure delivery system (APDS) applied controlled doses of pressure to scars in a red Duroc swine HTS model. Full-thickness wounds were created by a skin grafting instrument on each animal's bilateral flanks and were observed through reepithelialization and scar development. On day 70, the APDSs were mounted on the developed scars; right flank scars received a pressure of 30 mm Hg, while left flank scars received APDSs with no pressure (sham) for 2 weeks. A genome-wide assessment of compression effect on transcription in scar specimens before (early), shortly after (mid), and long after (late) compression initiation were performed., Results: Analysis of early-phase biopsies showed similar transcriptome profiles, which diverged thereafter in gene numbers and functions between compression- and sham-treated scars in the mid phase. The majority of these changes persisted in the late-phase scar samples. Canonical pathway analysis of differentially regulated genes resulted in an almost identical list of pathways during the early phase prior to compression. In the mid and late phases after compression, many of the identified pathways shifted in significance, and new pathways such as calcium signaling and cholesterol synthesis emerged., Conclusions: Compression modulates transcription and affects multiple biological functions associated with an improved scar appearance.

A large-scale online survey was designed to both inform and direct the development of an online community healthcare hub for people living with scarring. Focussed areas of questioning were generated to gather information on psychological symptoms, scar support and knowledge of wounds and healing. Simple statistical data was produced on the severity, aetiology and location of scarring. A secondary data analysis of the survey responses was conducted on more focussed themes. This survey was completed by 1034 people living with scars, 119 of which had burn scarring. The results highlight that patients with burn scars have higher levels of pre-existing psychological difficulties, carry a greater number of scars and experience more symptoms. A lack of support is identified for patients with scars once they have been discharged by their healthcare provider. The most popular forms of support were chosen as face-to-face interaction or online support. Key areas of support were found to be psychology particularly for help with acceptance or coping methods, wound care advice and meeting with other patients with scars. For these patients, key themes in the psychological impact of scarring include appearance-related concerns, social anxiety, acceptance and coping, experience of symptoms, skin viability and survivorship., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Hypertrophic scarring is a fibroproliferative process that occurs following a third-degree dermal burn injury, producing significant morbidity due to persistent pain, itching, cosmetic disfigurement, and loss of function due to contractures. Ablative fractional lasers have emerged clinically as a fundamental or standard therapeutic modality for hypertrophic burn scars. Yet the examination of their histopathological and biochemical mechanisms of tissue remodeling and comparison among different laser types has been lacking. In addition, deficiency of a relevant animal model limits our ability to gain a better understanding of hypertrophic scar pathophysiology. To evaluate the effect of ablative fractional lasers on hypertrophic third-degree burn scars, we have developed an in vivo Red Duroc porcine model. Third-degree burn wounds were created on the backs of animals, and burn scars were allowed to develop for 70 days before treatment. Scars received treatment with either CO2 or erbium: yttrium aluminum garnet (YAG) ablative fractional lasers. Here, we describe the effect of both lasers on hypertrophic third-degree burn scars in Red Duroc pigs. In this report, we found that Er:YAG has improved outcomes versus fractional CO2. Molecular changes noted in the areas of dermal remodeling indicated that matrix metalloproteinase 2, matrix metalloproteinase 9, and Decorin may play a role in this dermal remodeling and account for the enhanced effect of the Er:YAG laser. We have demonstrated that ablative fractional laser treatment of burn scars can lead to favorable clinical, histological, and molecular changes. This study provides support that hypertrophic third-degree burn scars can be modified by fractional laser treatment.

We hypothesised that a feedback mechanism of the transforming growth factor (TGF)-β1 signalling pathway, triggered by high-level TGF-β1, activates platelet-rich plasma (PRP) release to reduce connective tissue growth factor (CTGF) production and expression of CTGF mRNA in hypertrophic scar dermal fibroblasts. Primary dermal fibroblasts were isolated from cultures of hypertrophic scars. Cells were cultured after addition of serum-free Dulbecco's modified Eagle's medium supplemented with 5% (wt/vol) PRP or platelet-poor plasma (PPP). At 1, 4, 6, 8, 11, and 13 days after addition of PRP or PPP, the TGF-β1 and CTGF levels in supernatants were determined using solid-phase enzyme-linked immunosorbent assays. Quantitative reverse transcription polymerase chain reactions were performed to quantify TGF-β1 and CTGF mRNA expression levels. TGF-β1 mRNA expression in the PRP groups was lower than in the PPP groups from 4 to 13 days of culture, and there was statistically significant difference (P < .01). CTGF level and mRNA expression in the PRP groups was lower than in the PPP groups, and there were statistically significant differences (P < .01). Although further experiments will focus on clarifying the second messenger of the TGF-β1 negative feedback mechanism, the in vitro data presented show that PRP can potentially reduce CTGF and CTGF gene transcription by triggering the TGF-β1 signalling negative feedback mechanism., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: This study aimed to evaluate cross-cultural adaptation, validation, and reliability of Patient and Observer Scar Assessment Scale (POSAS) for its Turkish use., Method: This study included 50 burn patients with hypertrophic scars who were aged 18-65 years (mean, 37.5±1.4years) and were admitted to Wound and Burn Treatment Center from February 2014 to April 2014. With regard to the cultural adaptation of POSAS from English to Turkish, the scale was translated by two people who worked in different health fields. POSAS was administered to the patients with a 1-week interval to evaluate the validity and reliability of the scale. Internal consistency of the scale was tested using the Cronbach alphamethod., Results: The Cronbach alpha value for the observer measurements was found to be 0.93 (excellent), and that for patient measurements was found to be 0.77 (good). Accordingly, the internal consistency of the scale was established., Conclusion: The Turkish version of POSAS is a valid, reliable and culturally appropriate survey for evaluating hypertrophic scars. We believe that the Turkish version of POSAS will be an important clinical/scientific tool in the field of burn physiotherapy in Turkey, which will lead to new researches in this field., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Hypertrophic scar pain, pruritus, and paresthesia symptoms are major and particular concerns for burn patients. However, because no effective and satisfactory methods exist for their alleviation, the clinical treatment for these symptoms is generally considered unsatisfactory. Therefore, their risk factors should be identified and prevented during management. We reviewed the medical records of 129 postburn hypertrophy scar patients and divided them into two groups for each of three different symptoms based on the University of North Carolina "4P" Scar Scale: patients with scar pain requiring occasional or continuous pharmacological intervention (HSc pain, n = 75) vs. patients without such scar pain (No HSc pain, n = 54); patients with scar pruritus requiring occasional or continuous pharmacological intervention (HSc pruritus, n = 63) vs. patients without such scar pruritus (No HSc pruritus, n = 66); patients with scar paresthesia that influenced the patients' daily activities (HSc paresthesia, n = 31) vs. patients without such scar paresthesia (No HSc paresthesia, n = 98). Three multivariable logistic regression models were built, respectively, to identify the risk factors for hypertrophic burn scar pain, pruritus, and paresthesia development. Multivariable analysis showed that hypertrophic burn scar pain development requiring pharmacological intervention was associated with old age (odds ratio [OR] = 1.046; 95% confidence interval [CI], 1.011-1.082, p = 0.009), high body mass index (OR = 1.242; 95%CI, 1.068-1.445, p = 0.005), 2-5-mm-thick postburn hypertrophic scars (OR = 3.997; 95%CI, 1.523-10.487, p = 0.005), and 6-12-month postburn hypertrophic scars (OR = 4.686; 95%CI, 1.318-16.653, p = 0.017). Hypertrophic burn scar pruritus development requiring pharmacological intervention was associated with smoking (OR = 3.239; 95%CI, 1.380-7.603; p = 0.007), having undergone surgical operation (OR = 2.236; 95%CI, 1.001-4.998; p = 0.049), and firm scars (OR = 3.317; 95%CI, 1.237-8.894; p = 0.017). Finally, hypertrophic burn scar paresthesia development which affected the patients' daily activities was associated with age (OR = 1.038; 95%CI, 1.002-1.075; p = 0.040), fire burns (OR = 0.041; 95%CI, 0.005-0.366; p = 0.004, other burns vs. flame burns), and banding and contracture scars (OR = 4.705; 95%CI, 1.281-17.288, p = 0.020)., (© 2018 by the Wound Healing Society.)

General Purpose: To provide information about the clinical presentation of hypertrophic scars and keloids based on their varied structural components., Target Audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care., Learning Objectives/outcomes: After completing this continuing education activity, you should be able to: ABSTRACT: Hypertrophic scars and keloids are firm, raised, erythematous plaques or nodules that manifest when the cicatrix fails to properly heal. They result from pathologic wound healing and often cause pain and decreased quality of life. The appearance of such cosmetically unappealing scars affects the confidence and self-esteem of many patients. These scars can also cause dysfunction by interfering with flexion and extension across joints. Both possess some unique and distinct histochemical and physiologic characteristics that set them apart morphologically and at the molecular level. While these entities have been the focus of research for many years, differentiating between them remains challenging for clinicians.This article reviews the clinical presentation of aberrant scars and illustrates how they can be differentiated. It outlines their pathophysiology and emphasizes the unique molecular mechanisms underlying each disorder. It also examines how altered expression levels and the distribution of several factors may contribute to their unique clinical characteristics and presentation. Further research is needed to elucidate optimal treatments and preventive measures for these types of aberrant scarring.

Dear Readers, Itching (pruritus) of a wound, scar, or dermatologic disorder can negatively impact a patient's quality of life, resulting in injurious scratching1 or impeded rehabilitation.2 Like pain, itch can cause the su erer to lose sleep and appetite or even consider suicide.3,4 Clinical measures of pruritus have proved reliable and valid in individuals with burn wounds, dermatologic conditions, or urticaria5-7 or resulting scars,2 allowing studies to clarify its impact on human experience and compare the e ects of interventions to reduce itching. This Evidence Corner explores the e ects on pruritus of interventions applied at 2 very different stages of wound healing: the rst during early healing stages after hemorrhoidectomy8 and the other in postburn hypertrophic scarring with contracture.9 Each condition generates distressing levels of pruritus from which patients eagerly seek relief.

Hypertrophic scars/keloids are pathogenic scars that are characterized by collagen and fibroblast accumulation. The endothelia in the lesions are mechanosensitive and participate actively in the pathogenesis of these scars. The present review summarizes how endothelium responds to mechanical stimuli such as shear, stretch and hydrostatic pressure. It also shows that in heart, liver, kidney and lung fibrosis, endothelial dysfunctions (EDs) associate with changes in vascular tone, endothelial permeability, coagulation and vasomodulation that result in inflammation, hypertension and coagulation. Pathological scars exhibit similar EDs during their development and progression. Mechanopharmaceutical or mechanotherapeutic interventions that rescue EDs may be useful scar treatments., (© 2017 British Association of Dermatologists.)

Background: In hypertrophic scar assessment, laser Doppler imaging (LDI), colorimetry and subjective assessment (POSAS) can be used to evaluate blood flow, erythema and redness, respectively. In addition, the microvasculature (i.e. presence of microvessels) can be determined by immunohistochemistry. These measurement techniques are frequently used in clinical practice and/or in research to evaluate treatment response and monitor scar development. However, until now it has not been tested to what extent the outcomes of these techniques are associated, whilst the outcome terms are frequently used interchangeably or replaced by the umbrella term 'vascularization'. This is confusing, as every technique seems to measure a specific feature. Therefore, we evaluated the correlations of the four measurement techniques., Methods: We included 32 consecutive patients, aged ≥18 years, who underwent elective resection of a hypertrophic scar. Pre-operatively, we performed LDI (measuring blood flow), colorimetry (measuring erythema) and the POSAS (subjective redness) within the predefined scar area of interest (∼1.5cm). Subsequently, the scar was excised and the area of interest was sent for immunohistochemistry, to determine the presence of microvessels., Results: Only a statistically significant correlation was found between erythema values (colorimetry) and subjective redness assessment (POSAS) (r=0.403, p=0.030). We found no correlations between the outcomes of LDI, immunohistochemistry and colorimetry., Conclusions: Blood flow, the presence of microvessels and erythema appear to be different hypertrophic scar features because they show an absence of correlation. Therefore, in the field of scar assessment, these outcome terms cannot be used interchangeably. In addition, we conclude that the term 'vascularization' does not seem appropriate to serve as an umbrella term. The use of precise definitions in research as well as in clinical practice is recommended., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Hypertrophic scar is a major clinical outcome of deep-partial thickness to full thickness thermal burn injury. Appropriate animal models are a limitation to burn research due to the lack of, or access to, animal models which address the endpoint of hypertrophic scar. Lower species, such as rodents, heal mainly by contracture, which limits the duration of study. Higher species, such as pigs, heal more similarly to humans, but are associated with high cost, long duration for scar development, challenges in quantifying scar hypertrophy, and poor manageability. Here, we present a quantifiable deep-partial thickness burn model in the rabbit ear. Burns were created using a dry-heated brass rod for 10 and 20 seconds at 90 °C. At the time of eschar excision on day 3, excisional wounds were made on the contralateral ear for comparison. Burn wound progression, in which the wound size expands over time is a major distinction between excisional and thermal injuries, was quantified at 1 hour and 3 days after the injuries using calibrated photographs and histology and the size of the wounds was found to be unchanged from the initial wound size at 1 hour, but 10% in the 20 seconds burn wounds at 3 days. A quantifiable hypertrophic scar, measured by histology as the scar elevation index, was present in both 20 seconds burn wounds and excisional wounds at day 35. ImageJ measurements revealed that the 20 seconds burn wound scars were 22% larger than the excisional wound scars and the 20 seconds burn scar area measurements from histology were 26% greater than in the excisional wound scar. The ability to measure both burn progression and scar hypertrophy over a 35-day time frame suits this model to screening early intervention burn wound therapeutics or scar treatments in a burn-specific scar model., (© 2017 by the Wound Healing Society.)

Background: Keloid and hypertrophic scars represent an aberrant response to the wound healing process. These scars are characterized by dysregulated growth with excessive collagen formation, and can be cosmetically and functionally disruptive to patients., Objective: Objectives are to describe the pathophysiology of keloid and hypertrophic scar, and to compare differences with the normal wound healing process. The classification of keloids and hypertrophic scars are then discussed. Finally, various treatment options including prevention, conventional therapies, surgical therapies, and adjuvant therapies are described in detail., Materials and Methods: Literature review was performed identifying relevant publications pertaining to the pathophysiology, classification, and treatment of keloid and hypertrophic scars., Results: Though the pathophysiology of keloid and hypertrophic scars is not completely known, various cytokines have been implicated, including interleukin (IL)-6, IL-8, and IL-10, as well as various growth factors including transforming growth factor-beta and platelet-derived growth factor. Numerous treatments have been studied for keloid and hypertrophic scars,which include conventional therapies such as occlusive dressings, compression therapy, and steroids; surgical therapies such as excision and cryosurgery; and adjuvant and emerging therapies including radiation therapy, interferon, 5-fluorouracil, imiquimod, tacrolimus, sirolimus, bleomycin, doxorubicin, transforming growth factor-beta, epidermal growth factor, verapamil, retinoic acid, tamoxifen, botulinum toxin A, onion extract, silicone-based camouflage, hydrogel scaffold, and skin tension offloading device., Conclusion: Keloid and hypertrophic scars remain a challenging condition, with potential cosmetic and functional consequences to patients. Several therapies exist which function through different mechanisms. Better understanding into the pathogenesis will allow for development of newer and more targeted therapies in the future.

Scarring is the response elicited by the skin surface to injury and loss of tissue material. Wound healing takes place through a complex natural repair system consisting of vascular, inflammatory and proliferative phenomena, followed by a remodelling and cell apoptosis phase. This incredible repair system is inevitable, but sometimes unpredictable due to individual differences based on multiple factors. The scar is the objective criterion of a skin surgery, both for the patient and the dermsurgeon. It is therefore crucial to establish with the patient during the preoperative consultation, the size and positioning of the expected scar, taking into account the oncologic, anatomic and surgical constraints. Scars can ideally blend into normal skin, but may also give rise to various abnormalities. We can manage and prevent these abnormalities by mastering initial inflammation, that may induce hyperpigmentation and hypertrophy. Early massage using cortocosteroid topic or anti-inflammatory moisturizers may be effective. Random individual scarring may be minimized by a dynamic personalized accompanying scarring., (© 2016 Elsevier Masson SAS. Tous droits réservés.)

Improvements in acute burn care have enabled patients to survive massive burns that would have once been fatal. Now up to 70% of patients develop hypertrophic scars after burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. Approaches to optimise healing potential of burn wounds use targeted wound care and surgery to minimise the development of hypertrophic scarring. Such approaches often fail, and modulation of the established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventive and therapeutic strategies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Children have specific characteristics of wound healing. The aim of this study was to describe the specific clinical characteristics of wounds healing in children and to present the current knowledge on the specific mechanisms with regard to infant age. The tissue insult or injury in fetus can heal without scar, mainly due to reduced granulation tissue associated to diminished or even no inflammatory phase, modified extracellular matrix such as the concentration of hyaluronic acid in amniotic liquid, expression and arrangement of collagen and tenascin. Thickness of children skin is a serious negative factor in case of trauma, whereas poor co-morbidities and efficient growth tissue mechanisms are beneficial to good evolution, even in cases of extensive damage and loss of tissue. The subsequent tissue mechanical forces, wound healing during childhood, spanning from the age of 2 until the end of puberty, is associated with more hypertrophic scars, both in duration and in intensity. Consequently, unnecessary surgery has to be avoided during this period when possible, and children with abnormal or pathologic wound healing should benefit from complementary treatments (hydration, massage, brace, silicone, hydrotherapy…), which represent efficient factors to minimize tissue scarring. After wound healing, the growth body rate can be responsible for specific complications, such as contractures, alopecia, and scar intussusceptions. Its evolutionary character implies the need of an attentive follow-up until adult age. Psychologic repercussions, as a consequence of pathologic scars, must be prevented and investigated by the surgeon., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Animal models are crucial for the study of fibrosis. Keloids represent a unique type of fibrotic scarring that occurs only in humans, thus presenting a challenge for those studying the pathogenesis of this disease and its therapeutic options. Here, several animal models of fibrosis currently in use are described, emphasizing recent progress and highlighting encouraging challenges., (Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.)

Mechanical strain is a key contributor in the pathogenesis of hypertrophic scarring, whose optimal stretch magnitudes to initiate the differentiation of normal skin fibroblasts into aberrant fibroblasts phenotype remains largely unresolved. Influence of varying cyclic strain magnitudes on cultured human normal skin fibroblasts and its transformation into hypertrophic scar fibroblast-like phenotype is investigated in this study. Cultured fibroblasts isolated from hypertrophic scar and normal skin tissue were subjected to cyclic mechanical stretching under individual 10%, 15%, and 20% strain magnitudes at a frequency of 0.1 Hz for 24 hours. Stretched normal skin fibroblasts demonstrated significantly increased rates of cell proliferation, and also apparently oriented away nearly perpendicular to the applied stretching direction. Interestingly, the applied 10% strains magnitude resulted in a markedly enhanced cell proliferative ability compared with that of 20% strain magnitude. Parameters involving the mechanotransduction signaling, such as integrin β1 and P130Cas, were significantly improved at both mRNA and protein levels in the stretched normal skin fibroblasts, which was demonstrated in a negative magnitude-dependent manner. In addition, 10% strains magnitude triggered the highest expression levels of growth factor TGF-β1 and collagen matrix in stretched normal skin fibroblasts. Collectively, these results indicate that the 10% stretching magnitude, of the 3 strain magnitudes studied, is most effective for triggering the optimal mechanotransduction effects and biological responses inside cultured skin fibroblasts. The demonstrable conversion of normal skin fibroblasts into hypertrophic scar fibroblasts was also observed when 10% stretching magnitude was applied to cultured fibroblasts in vitro.

Hypertrophic scar (HS) is characterized by fibroblast hyperproliferation and excessive matrix deposition. Aberrant keratinocyte differentiation and their abnormal cytokine secretion are said to contribute to HS by activating fibroblasts. However, the signalling pathway causing the aberrant keratinocytes in HS has remained unidentified thus far. Given that Notch signalling is crucial in initiating keratinocyte differentiation, we hypothesized that Notch signalling contributes to HS by modulating the phenotype of keratinocytes. We found that Notch1, Notch intracellular domain, Jagged1 and Hes-1 were overexpressed in the epidermis of patients with HS. Supernatants from recombinant-Jagged1-treated keratinocyte cultures could accelerate dermal fibroblast proliferation and collagen production. Furthermore, Jagged1 induced keratinocyte differentiation and upregulated the expression of fibrotic factors, including transforming growth factors β1 and β2 , insulin-like growth factor-1, connective tissue growth factor, vascular endothelial growth factor and epidermal growth factor, while DAPT (a Notch inhibitor) significantly suppressed these processes. In a rabbit ear model of HS, local application of DAPT downregulated the production of fibrotic factors in keratinocytes, together with ameliorated scar hyperplasia. Our findings suggest that Notch signalling contributes to HS by modulating keratinocyte phenotype. These results provide new insights into the pathogenesis of HS and indicate a potential therapeutic target., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lateral contracture of the neck is a rare and insufficiently researched burn consequent. Contracture restricts head motion, can cause a secondary face deformity, presents severe cosmetic defects, and, therefore, requires surgical reconstruction. Literature does not sufficiently address the issue; therefore, anatomy not researched and treatment techniques not developed. The anatomy of postburn lateral cervical flexion contracture was studied in 21 operated patients. Using obtained data, new approaches were investigated, which were directed toward maximal efficacy of the local tissues use. Follow-up results were observed from 6 months to 9 years. Lateral cervical contractures were divided into two types based on their anatomy: edge and medial. Edge contractures were caused by burns and scars located on the posterior neck surface and were characterized by the presence of the fold in central lateral zone. In the fold, only one (posterior) sheet is scars that cause the contracture. Medial contractures were caused by scars located on the lateral cervical surface and were characterized by the presence of the fold in which both sheets were scars. In both types, contracture was caused by scar sheet surface deficiency in length, which has a trapezoid form (contracture cause). In all cases, there was surface surplus in the fold's sheets allowed contracture release with local tissue. The technique that allows the maximum local tissue use and ensures full contracture elimination is the trapeze-flap plasty. Two anatomic types of lateral cervical scar contractures were identified: edge and medial. An anatomically justified efficacy reconstructive technique for both types is trapeze-flap plasty.

Wound healing process is a complex and highly orchestrated process that ultimately results in the formation of scar tissue. Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts in vitro. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NFκB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NFκB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels in vivo. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring.

Hypertrophic scars are characterized by excessive fibrosis and extracellular matrix (ECM) deposition and can be functionally and cosmetically problematic; however, there are few satisfactory treatments for controlling hypertrophic scars. The inflammatory cells and cytokines involved in excessive inflammation during wound healing facilitate fibroblast proliferation and collagen deposition, leading to pathologic scar formation. TSG-6 exhibits anti-inflammatory activity. This study examined the effect of recombinant TSG-6 on inflammation in hypertrophic scars using a rabbit ear model. Six 7-mm, full-thickness, circular wounds were made on the ears of 12 rabbits. TSG-6 and PBS were intradermally injected into the right and left ear wounds, respectively. The methods of TEM and TUNEL were used to detect fibroblast apoptosis. The expressions of inflammatory factors: IL-1β, IL-6 and TNF-α, were detected by immunohistochemistry and real time polymerase chain reaction. Collagen I and III expression detected by immunohistochemistry and Masson׳s trichrome staining and SEI (scar elevation index) was used to evaluate the extent of scarring. TSG-6 injection mitigated the formation of a hypertrophic scar in the rabbit ear. TSG-6-treated wounds exhibited decreased inflammation compared with the control group, as evidenced by the lower levels of IL-1β, IL-6, TNF-α and MPO. The SEI and the synthesis of collagens I and III were significantly decreased in the TSG-6-treated scars compared with control scars. The apoptosis rate was higher in the TSG-6-treated scars. TSG-6 exhibited anti-inflammatory effects during the wound healing process and cicatrization and significantly diminished hypertrophic scar formation in a rabbit ear model., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ginsenoside, one of the active compounds in Panax ginseng, inhibits tumor growth factor-beta 1 (TGF-β1) and reduces the level of collagen type 1. Ginsenoside Rb1 promotes burn wound healing. Our study evaluated the effects of ginsenoside Rb1 on hypertrophic scar remodeling. A total of 72 hypertrophic scars were generated on the ears of six New Zealand white rabbits. Treatment groups were administered with intradermal injections of ginsenoside Rb1 at various amounts (0.07mg, 0.28mg and 0.56mg), and evaluated on postoperative Day 35. Scar elevation index was used as a quantitative measure, and picrosirius staining of histological sections was used to assess collagen arrangement. We determined relative mRNA expression of collagen type 1 as well as scar related factors; matrix metalloproteinase 2 (MMP2), tissue-inhibitor of metalloproteinase 1 (TIMP1), alpha-smooth muscle actin (α-SMA), and TGF-β1. Immunohistochemistry assays were performed additionally. Application of 0.56mg of ginsenoside Rb1 resulted in significant decrement of scar elevation index, in comparison with control and lower dosage groups, furthermore achieved broader and randomly arranged collagen fibers resembling findings in normal dermis. Ginsenoside Rb1 concentration inversely correlated with the mRNA expression and immunohistochemical reactivity of scar related factors; MMP2, TIMP1, α-SMA, and TGF-β1. In addition, ginsenoside Rb1 suppressed collagen type 1 expression. Ginsenoside Rb1 is therapeutic in hypertrophic scar remodeling with the highest efficacy at 0.56mg of dosage. Ginsenoside Rb1 demonstrated inhibitory effects on hypertrophic scar in quantitative and histologic analysis. Further research is needed to determine optimal ginsenoside Rb1 application and exposure conditions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The four-herb Chinese medicine ANBP is a pulverized mixture of four herbs including Agrimonia Eupatoria (A), Nelumbo Nucifera Gaertn (N), Boswellia Carteri (B) and Pollen Typhae Angustifoliae (P). The combination of the four herbs was first described in Chinese canonical medicine about 2000 years ago for treatment of various trauma disorders, such as hemostasis, antiinflammatory, analgesia, and wound healing, etc. However, the precise mechanisms of ANBP are still unclear. In our study, using rabbit ear hypertrophic scar models of full-thickness skin defect, we showed that local ANBP treatment not only significantly enhanced wound healing by relieving inflammation, increasing formation of granulation tissue and accelerating re-epithelialization, but also reduced scar formation by decreasing collagen production, protuberant height and volume of scars, and increasing collagen maturity. We demonstrated that these effects of ANBP are associated with transforming growth factor (TGF)-β1-mediated signalling pathways through Smad-dependent pathways. ANBP treatment significantly increased expression of TGF-β1 and Smad2/3 mRNA at the early stage of wound healing, and led to markedly decrease expression of TGF-β1 and Smad2/3 compared with the control group after 14 days post-wounding. Taken together, our results defined a bidirectional regulation role of ANBP for TGF-β1/Smad pathway in promoting wound healing and alleviating scar formation, which may be an effective therapy for human wounds at the earliest stage.

We have yet to create a human scar model that demonstrates the complex nature of hypertrophic scar and keloid formation as well as ways to prevent them despite emerging advances in our understanding of the immune system, the inflammatory response, and proteomic and genomic changes after injury. Despite more complex in vitro models, we fail to explain the fundamental principles to scar formation, and the timeline of their development. The solution to developing the ideal in vitro scar model is one that mimics the heterogeneous cellular and molecular interactions, as well as the evolving structure and function of human skin., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Activation of transforming growth factor-β (TGF-β) signaling and matrix metalloproteinases are involved in hypertrophic scar (HS) formation. Compression therapy is known to be an effective approach for the treatment of hypertrophic scarring; however, the underlying molecular mechanisms remain poorly understood. We investigated the relationship between TGF-β signaling activation and matrix metalloproteinases in HS fibroblasts during mechanical compressive stress., Materials and Methods: Two groups of skin tissue from HS and the nearby normal tissue were obtained from surgical patients and analyzed. Primary fibroblasts from the HS tissue and normal fibroblasts were isolated. Pressure therapy was recapitulated in an in vitro three-dimensional culture model, using mechanical stress produced with the Flexcell FX-4000C Compression Plus System. Quantitative real-time PCR (qPCR) was used to analyze the gene expression profiles in skin tissue and cultured primary cells exposed to compressive stress. Knockdown of SMAD2 and SMAD3 was performed using their specific siRNA in HS and normal fibroblasts subjected to compressive stress, and gene expression was examined by qPCR and Western blot., Results: There was a significant upregulation of the mRNA expression of matrix metalloproteinase-2 (MMP2) and MMP9 in primary HS fibroblasts in response to mechanical stress. In contrast, the mRNA levels of collagen I and collagen III were downregulated in primary HS fibroblasts compared with those in the control cells. SiRNA-mediated knockdown of SMAD3 in the primary fibroblasts exposed to mechanical stress resulted in a decrease in the expression of MMP9 compared to control cells., Conclusion: These results demonstrate that compressive stress upregulates MMP9 by SMAD3 but not by SMAD2.

The cutaneous wound-healing process can lead to hypertrophic scar formation, during which exaggerated inflammation has been demonstrated to have an important role. Therefore, an exploration of strategies designed to regulate this inflammatory process is warranted. Mesenchymal stem cells (MSCs) have recently been demonstrated to regulate inflammation in various diseases. In this regard, using a rabbit model, we locally injected human mesenchymal stem cells (hMSCs) derived from bone marrow to treat hypertrophic scar formation, and explored their underlying mechanisms. We found that hMSC therapy efficiently regulated inflammation and prevented scar formation. We attributed the therapeutic effects of hMSCs to their secretion of an anti-inflammatory protein, TNF-alpha-stimulated gene/protein 6 (TSG-6). Unexpectedly, after injection, the number of surviving hMSCs decreased markedly and the hMSCs underwent extensive apoptosis, which was demonstrated to promote their secretion of TSG-6, partially through the activation of caspase-3. Moreover, H2O2-induced apoptotic hMSCs showed higher inflammatory regulatory abilities. The inhibition of caspase-3 decreased the inflammatory regulatory abilities of hMSCs and attenuated their therapeutic effects. Our results demonstrate that hMSCs can efficiently prevent hypertrophic scar formation via inflammatory regulation. In addition, we found that apoptosis has an important role in the activation of the inflammatory regulatory abilities of hMSCs.

Hypertrophic scarring is extremely common and is the source of most morbidity related to burns. The biology of hypertrophic healing is complex and poorly understood. Multiple host and injury factors contribute, but protracted healing of partial thickness injury is a common theme. Hypertrophic scarring and heterotopic ossification may share some basic causes involving marrow-derived cells. Several traditional clinical interventions exist to modify hypertrophic scar. All have limited efficacy. Laser interventions for scar modification show promise, but as yet do not provide a definitive solution. Their efficacy is only seen when used as part of a multimodality scar management program., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Most cutaneous wounds heal with scar formation. Ideally, an inconspicuous normotrophic scar is formed, but an abnormal scar (hypertrophic scar or keloid) can also develop. A major challenge to scientists and physicians is to prevent adverse scar formation after severe trauma (e.g. burn injury) and understand why some individuals will form adverse scars even after relatively minor injury. Currently, many different models exist to study scar formation, ranging from simple monolayer cell culture to 3D tissue-engineered models even to humanized mouse models. Currently, these high-/medium-throughput test models avoid the main questions referring to why an adverse scar forms instead of a normotrophic scar and what causes a hypertrophic scar to form rather than a keloid scar and also, how is the genetic predisposition of the individual and the immune system involved. This information is essential if we are to identify new drug targets and develop optimal strategies in the future to prevent adverse scar formation. This viewpoint review summarizes the progress on in vitro and animal scar models, stresses the limitations in the current models and identifies the future challenges if scar-free healing is to be achieved in the future., (© 2014 The Authors. Experimental Dermatology. Published by John Wiley & Sons Ltd.)

Objective: To investigate the role of mast cells and vascular endothelial growth factor (VEGF) as a mediator of angiogenesis to promote wound healing in surgical and pathological scars., Study Design: The study was carried out on 40 patients who presented with active scar lesions. They were subdivided into 4 groups. They included granulation tissue (10 cases), surgical scar (10 cases), hypertrophic scar (10 cases), and keloid scar (10 cases). Also 10 healthy volunteers of the same age and sex were selected as a control group. Skin biopsies were taken from the patients and the control group. Skin biopsies from clinically assessed studied groups were processed for routine histology and embedded in paraffin. Four sections were prepared from each paraffin block. The first section was stained with hematoxylin and eosin for histological evaluation. The second and third sections were processed for immunostaining of mast cells that contain chymase (MCCs) and mast cells that contain tryptase (MCTs). The fourth section was processed for immunostaining of VEGF., Results: MCCs exhibited mild expression in normal tissue, granulation tissue, and surgical, hypertrophic and keloid scars. MCTs exhibited mild expression in normal tissue, granulation tissue and keloid, whereas moderate expression was exhibited in hypertrophic and surgical scars. VEGF expression was absent in normal tissue, mild in keloid, surgical and hypertrophic scars, and moderate in keloids and granulation tissue., Conclusion: Mast cell expression variation among different scar types signals the pathological evolution of the lesion, and hence may guide the need for therapeutic intervention.

Despite the worldwide use of silicones in scar management, its exact working mechanism based on a balanced occlusion and hydration, is still not completely elucidated. Moreover, it seems peculiar that silicones with completely different occlusive and hydrating properties still could provide a similar therapeutic effect. The objective of the first part of this study was to compare the occlusive and hydrating properties of three fluid silicone gels and a hydrating gel-cream. In a second part of the study these results were compared with those of silicone gel sheets. Tape stripped skin was used as a standardized scar like model on both forearms of 40 healthy volunteers. At specific times, trans epidermal water loss (TEWL) and the hydration state of the stratum corneum were measured and compared with intact skin and a scar-like control over a 3-4h period. Our study clearly demonstrated that fluid silicone gels and a hydrating gel-cream have comparable occlusive and hydrating properties while silicone gel sheets are much more occlusive, reducing TEWL values far below those of normal skin. A well-balanced, hydrating gel-cream can provide the same occlusive and hydrating properties as fluid silicone gels, suggesting that it could eventually replace silicones in scar treatment., (Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.)

Burn injury-mediated destruction of the skin barrier normally induces microbial invasion, in turn leading to the development of systemic infection and occasional septic shock by the release of endotoxins. The objective of this work was to study the influence of lipopolysaccharide (LPS) on the biological characteristics of normal skin fibroblasts and to elucidate the influence of LPS in the initial stage of skin wound healing. Twenty patients with hypertrophic scar in proliferative stage were selected randomly and primary cultures were established from fibroblasts derived from their hypertrophic scar tissue and normal skin. Normal skin fibroblasts of passage 3 were stimulated with different concentrations of LPS. LPS stimulated the proliferation and collagen synthesis of fibroblasts within a certain extent of concentrations (0.005-0.5 μg/mL) (P < 0.05), whereas at a concentration of 1 μg/mL inhibited the proliferation and collagen synthesis of fibroblasts (P < 0.05). Collagen synthesis by normal skin fibroblasts after LPS stimulation mimicked those derived from hypertrophic scar tissue. LPS of 0.1 μg/mL had significant effect on normal skin fibroblasts-continuous passage of these fibroblasts resulted in ultrastructural pattern similar to fibroblasts derived from hypertrophic scar tissue, and the findings was substantiated by hematoxylin and eosin staining and immunohistochemistry detection of proliferation cell nuclear antigen, type I procollagen and α-smooth muscle actin. Our results suggest that LPS might convert normal skin fibroblasts to hypertrophic scar tissue fibroblasts and participate in the formation of hypertrophic scar; hence, appropriate concentration of LPS may have no effect or be beneficial to skin wound healing, whereas excessive concentration of LPS may delay the time of wound healing., (Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.)

Background: The prominent inflammatory cell identified in excessive scarring is the mast cell. Hypertrophic scar exhibits myofibroblasts derived from the transformation of fibroblasts, increased collagen synthesis, and stationary nonmigratory resident cells. The co-culture of fibroblasts with an established rat mast cell line (RMC-1) was used to explore the hypothesis of whether mast cells through gap junctional intercellular communications guide fibroblasts in promoting excessive scarring., Methods: Human dermal fibroblasts were cultured alone or co-cultured with RMC-1 cells as is or with either blocked gap junctional intercellular communications or devoid of cytoplasmic granules. Collagen synthesis was analyzed by dot blot analysis; immunohistology identified myofibroblasts, and a cell migration assay measured fibroblast locomotion., Results: Fibroblasts co-cultured with RMC-1 cells transformed into myofibroblasts, had increased collagen synthesis, and showed retarded cell migration. In contrast, RMC-1 cells unable to form gap junctional intercellular communications were similar to fibroblasts alone, failing to promote these activities. Degranulated RMC-1 cells were as effective as intact RMC-1 cells., Conclusions: Mast cells induce fibroblast activities associated with hypertrophic scarring through gap junctional intercellular communications. Eliminating the mast cell or its gap junctional intercellular communications with fibroblasts may be a possible approach in preventing hypertrophic scarring or reducing fibrotic conditions.