Skin Scar Tissue Research Articles

Alpha-boswellic acid accelerates acute wound healing via NF-κB signaling pathway.

Boswellic acids (BAs) showed promising effects in cancer treatment, immune response regulation, and anti-inflammatory therapy. We aimed to assess the roles of alpha-BA (α-BA) in treating acute wound healing. In vivo wound-healing models were established to evaluate the therapeutic effects of α-BA. Cell assays were conducted to assess the impact of α-BA on cellular biological functions. Western blot analysis was employed to validate the potential mechanisms of action of α-BA. Animal models indicated that wound healing was notably accelerated in the α-BA group compared to the control group (P < 0.01). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) assay preliminarily suggested that α-BA may accelerate wound healing by inhibiting excessive inflammatory reactions and increasing the protein levels of growth factors. Cell function experiments demonstrated that α-BA suppressed the proliferation and migration ability of human hypertrophic scar fibroblasts (HSFBs), thereby favoring wound healing. Additionally, α-BA exerted a significant impact on cell cycle progression. Mechanistically, the protein levels of key genes in nuclear factor kappa beta (NF-κB) signaling pathway, including cyclin D1, p65, IκBα, and p-IκBα, were downregulated by α-BA. α-BA demonstrated the ability to counteract the abnormal proliferation of skin scar tissues, consequently expediting wound healing. These findings suggest its potential for development as a new agent for treating acute wound healing.

MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-β2 to suppress the TGF-β2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-β2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

IGFBP-7 secreted by adipose-derived stem cells inhibits keloid formation via the BRAF/MEK/ERK signaling pathway

BackgroundAdipose tissue-derived stem cells (ASCs) have important clinical significance as regulators of skin scar tissue regeneration. ASCs inhibit keloid formation and increase insulin-like growth factor-binding protein-7 (IGFBP-7) expression. However, whether ASCs inhibit keloid formation through IGFBP-7 remains unclear. ObjectiveWe aimed to assess the roles of IGFBP-7 in keloid formation. MethodsWe analyzed the proliferation, migration, and apoptosis of keloid fibroblasts (KFs) treated with recombinant IGFBP-7 (rIGFBP-7) or by co-culture with ASCs using CCK8 assays, transwell assays, and flow cytometry, respectively. In addition, immunohistochemical staining, quantitative polymerase chain reaction, human umbilical vein endothelial cell tube formation, and western blotting experiments were used to assess keloid formation. ResultsIGFBP-7 expression was significantly lower in keloid tissues than that in normal skin tissues. Stimulation of KFs with rIGFBP-7 at different concentrations or by co-culture with ASCs resulted in decreased KF proliferation. Additionally, KF stimulation with rIGFBP-7 resulted in increased apoptosis of KFs. IGFBP-7 also reduced angiogenesis in a concentration-dependent manner, and stimulation with different rIGFBP-7 concentrations or co-culture of KFs with ASCs inhibited the expression of transforming growth factor-β1, vascular endothelial growth factor, collagen I, interleukin (IL)-6, IL-8, B-raf proto-oncogene (BRAF), mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK) in KFs. ConclusionCollectively, our findings suggested that ASC-derived IGFBP-7 prevented keloid formation by inhibiting the BRAF/MEK/ERK signaling pathway.

Hyperosmolar Potassium Inhibits Corneal Myofibroblast Transformation and Prevent Corneal Scar

PurposeCorneal myofibroblasts play a crucial role in the process of corneal scarring. Potassium has been documented to reduce skin scar tissue formation. Herein, we investigated the ability of potassium to prevent corneal fibrosis in cell culture and in vivo.MethodsCorneal fibroblasts (CFs) were isolated from the corneal limbus and treated with TGF-β1 to transform into corneal myofibroblasts. Corneal myofibroblast markers were detected by quantitative real-time PCR, Western blot, and immunofluorescence. The contractive functions of corneal myofibroblast were evaluated by the scratch assay and the collagen gel contraction assay. RNA sequencing in corneal fibroblasts was performed to explore the mechanisms underlying hyperosmolar potassium treatment. GO and KEGG analysis were performed to explore the underlying mechanism by hyperosmolar potassium treatment. The ATP detection assay assessed the level of cell metabolism. KCl eye drops four times per day were administered to mice models of corneal injury to evaluate the ability to prevent corneal scar formation. Corneal opacity area was evaluated by Image J software.ResultsTreatment with hyperosmolar potassium could suppress corneal myofibroblast transformation and collagen I synthesis induced by TGF-β1 in cell culture. Hyperosmolar potassium could inhibit wound healing and gel contraction in CFs. RNA sequencing results suggested that genes involved in the metabolic pathway were downregulated after KCl treatment. ATP levels were significantly decreased in the KCl group compared with the control group. Hyperosmolar potassium could prevent corneal myofibroblast transformation after corneal injury and corneal scar formation in mice.ConclusionPotassium can suppress corneal myofibroblast transformation and collagen I protein synthesis. Moreover, given that KCl eye drops can prevent corneal scar formation, it has been suggested to have huge prospects as a novel treatment approach during clinical practice.

The Correlation between Serum Cortisol Levels with Stretch Marks in Gymnastic Male

BACKGROUND: Stretch marks are skin scar tissue that appears in the form of purplish linear atrophy, erythematous or hypopigmented which is often caused by excessive stretching of the skin. Increased cortisol levels can cause an increase in collagen degradation which results in disruption of the extracellular matrix in the dermis, resulting in stretch marks. Physical stress can trigger activation of the hypothalamic-pituitary-adrenal axis, which will induce activation of stress hormones, including cortisol in the adrenal cortex. AIM: The objective of the study is to determine the correlation between serum cortisol levels and stretch marks in male at a gymnastics training site. SUBJECTS AND METHODS: Observational analytic study with a cross-sectional approach to 50 stretch marks subjects. RESULTS: Serum cortisol levels of subjects with stretch marks averaged 9.72 g/dL with the lowest level of 4.45 g/dL and the highest level of 49.25 g/dL (p &lt; 0.001). The highest age with stretch marks was 26–30 years 18 (36%) subjects and the lowest age was aged 36–40 years 5 (10%) subjects. The majority of stretch marks are located in the axillary region (30.9%), brachii (23.6%), and abdomen (18.4%). The average cortisol level in subjects with aerobic exercise was 6.52 g/dL, muscle training 11.18 g/dL, mixed aerobic and muscle training 7.5 g/dL. The highest average cortisol levels were at exercise duration of 31–60 min of 12.88 g/dL, 61–90 min of 6.63 g/dL, and 91–120 min of 6.2 g/dL. The highest frequency of exercise in a week was 3–4 times as many as 30 subjects (60%) with an average serum cortisol level of 11.1879 g/dL. CONCLUSION: There is a significant correlation between serum cortisol levels and stretch marks in male at gymnastics training.

Efficacy and safety of umbilical cord mesenchymal stem cells in treatment of cesarean section skin scars: a randomized clinical trial

BackgroundPathological skin scars, caused by cesarean section, affected younger mothers esthetically and psychosocially and to some extent frustrated obstetricians and dermatologists. Umbilical cord mesenchymal stem cells (UC-MSCs), as a population of multipotent cells, are abundant in human tissues, providing several possibilities for their effects on skin scar tissues. Herein, we performed a randomized, double-blind, placebo-controlled, three-arm clinical trial, aiming to assess the efficacy and safety of UC-MSCs in the treatment of cesarean section skin scars among primiparous singleton pregnant women.MethodsNinety primiparous singleton pregnant women undergoing elective cesarean section were randomly allocated to receive placebo, low-dose (3 × 106 cells), or high-dose (6 × 106 cells) transdermal hydrogel UC-MSCs on the surface of the skin incision. The primary outcome was cesarean section skin scars followed after the sixth month, assessed by the Vancouver Scar Scale (VSS).ResultsAll the participants completed their trial of the primary outcome according to the protocol. The mean score of estimated total VSS was 5.52 in all participants at the sixth-month follow-up, with 6.43 in the placebo group, 5.18 in the low-dose group, and 4.71 in the high-dose group, respectively. No significant difference was found between-group in the mean scores for VSS at the sixth month. Additional prespecified secondary outcomes were not found with significant differences among groups either. No obvious side effects or adverse effects were reported in any of the three arms.ConclusionThis randomized clinical trial showed that UC-MSCs did not demonstrate the effects of improvement of cesarean section skin scars.Trial registrationClinicalTrials.gov identifier, NCT02772289. Registered on 13 May 2016.

Promotion of Fibrosis in Skin Scar Tissue by Secreted Protein Acidic Which is Rich in Cysteine Proteins

Promotion of Fibrosis in Skin Scar Tissue by Secreted Protein Acidic Which is Rich in Cysteine Proteins

Genetically-modified bone mesenchymal stem cells with TGF-β3 improve wound healing and reduce scar tissue formation in a rabbit model

Extensive scar tissue formation often occurs after severe burn injury, trauma, or as one of complications after surgical intervention. Despite significant therapeutic advances, it is still a significant challenge to manage massive scar tissue formation while also promoting normal wound healing. The goal of this study was to investigate the therapeutic effect of bone mesenchymal stem cells (BMSCs) that were genetically modified to overexpress transforming growth factor-beta 3 (TGF-β3), an inhibitor of myofibroblast proliferation and collagen type I deposition, on full-thickness cutaneous wound healing in a rabbit model. Twenty-four rabbits with surgically-induced full-thickness cutaneous wounds created on the external ear (1.5 × 1.5 cm, two wounds/ear) were randomized into four groups: (G1), wounds with no special treatment but common serum-free culture medium as negative controls; (G2), topically-applied recombinant adenovirus, expressing TGF-β3/GFP; (G3), topically-applied BMSCs alone; (G4), topically-applied BMSCs transfected with Ad-TGF-β3/GFP (BMSCsTGF-β3); and (G5), an additional normal control (n = 2) with neither wound nor treatment on the external ear skin. The sizes of wounds on the ear tissues were grossly examined, and the scar depth and density of wounds were histologically evaluated 21, 45, and 90 days after surgical wound creation. Our results demonstrated that G4 significantly reduced the wound scar depth and density, compared to G1~3. Numbers of cells expressing GFP significantly increased in G4, compared to G2. The protein expression of TGF-β3 and type III collagen in G4 significantly increased, while the ratio of type I to type III collagen was also significantly reduced, which is similar to the tissue architecture found in G5, as compared the other treatment groups. In conclusion, transplantation of BMSCsTGF-β3 remarkably improves wound healing and reduces skin scar tissue formation in an animal model, which may potentially provide an alternative in the treatment of extensive scar tissue formation after soft tissue injury.

Neutrophil extracellular traps promote differentiation and function of fibroblasts.

Neutrophil activation by inflammatory stimuli and the release of extracellular chromatin structures (neutrophil extracellular traps - NETs) have been implicated in inflammatory disorders. Herein, we demonstrate that NETs released by neutrophils treated either with fibrosis-related agents, such as cigarette smoke, magnesium silicate, bleomycin, or with generic NET inducers, such as phorbol 12-myristate 13-acetate, induced activation of lung fibroblasts (LFs) and differentiation into myofibroblast (MF) phenotype. Interestingly, the aforementioned agents or IL-17 (a primary initiator of inflammation/fibrosis) had no direct effect on LF activation and differentiation. MFs treated with NETs demonstrated increased connective tissue growth factor expression, collagen production, and proliferation/migration. These fibrotic effects were significantly decreased after degradation of NETs with DNase1, heparin or myeloperoxidase inhibitor, indicating the key role of NET-derived components in LF differentiation and function. Furthermore, IL-17 was expressed in NETs and promoted the fibrotic activity of differentiated LFs but not their differentiation, suggesting that priming by DNA and histones is essential for IL-17-driven fibrosis. Additionally, autophagy was identified as the orchestrator of NET formation, as shown by inhibition studies using bafilomycin A1 or wortmannin. The above findings were further supported by the detection of NETs in close proximity to alpha-smooth muscle actin (α-SMA)-expressing fibroblasts in biopsies from patients with fibrotic interstitial lung disease or from skin scar tissue. Together, these data suggest that both autophagy and NETs are involved not only in inflammation but also in the ensuing fibrosis and thus may represent potential therapeutic targets in human fibrotic diseases.

The Long-Term Follow-Up Results of External Dacryocystorhinostomy Skin Incision Scar with “W Incision”

Objective: To determine the effect of “W incision” instead of classical vertical incision at external DCR on scar formation.Materials and Methods: Patients with acquired nasolacrimal duct obstruction (NLDO) who were treated with external DCR with classical vertical incision, and patients who were treated with external DCR with “W incision” were included in the study. The first 39 eyes were operated with a vertical incision, and the remaining 37 eyes were operated with a “W incision”. All the skin incision scars of the patients were assessed and scored by at least the 6th month. The assessment was made by both the patients themselves, and by an ophthalmologist other than the surgeon himself, each scored the incision scar separately (single-masked study). Scores for both groups were compared, and statistical analyses were performed.Results: Self-assessment scores for the incision scar were Grade 2.28 ± 0.94 in the Vertical incision group, and Grade 1.68 ± 0.57 in the “W incision” group (p < 0.01). The “W incision” scar formation was significantly less noticable than the Vertical incision scar formation. Similarly, the assessment scores of the ophthalmologist other than the surgeon himself were significantly lower for the “W incision” group than for the Vertical incision group. The mean scar assessment scores were Grade 2.13 ± 0.95 in the Vertical incision group, and Grade 1.57 ± 0.68 in the “W incision” group (p < 0.01).Conclusion: Skin scar tissue was found to be significantly reduced with a “W incision” in external DCR operations.

Differential scanning calorimetric examination of pathologic scar tissues of human skin

Keloid and hypertrophic scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen. Excess scar formation occurs after dermal injury as a result of abnormal wound healing. Keloid formation has been ascribed to altered growth factor regulation, aberrant collagen turnover, genetics, immune dysfunction, sebum reaction, and altered mechanics. No single hypothesis adequately explains keloid formation. The thermal denaturations of pathologic human skin scar tissues were monitored by a SETARAM Micro DSC-II calorimeter. All the experiments were performed between 0 and 100 °C. The heating rate was 0.3 K min−1. DSC scans clearly demonstrated significant differences between the different types and conditions of samples (intact skin: T m = 54.8 °C and ΔH cal = 4.5 J g−1; normal scar: T m = 53.8 °C and ΔH cal = 4.2 J g−1; hypertrophic scar: T m = 54.2 °C and ΔH cal = 2.4 J g−1; keloid: T m = 52.9 °C and ΔH cal = 8.3 J g−1). The heat capacity change between native and denatured states of samples increased with the degree of structural alterations indicating significant water loosing. These observations could be explained with the structural alterations caused by the biochemical processes. With our investigations, we could demonstrate that DSC is a useful and well-applicable method for the investigation of collagen tissue of the human keloid and hypertrophic scar tissues. Our results may be of clinical relevance in the future, i.e., in the diagnosis of the two different pathologic scar formations, or in the choice of the optimal therapy of the disease.

Pre‐operative and Operative Difficulties During Bovine Caesarean Section in Belgium and Associated Risk Factors

The aim of this study was to describe the difficulties encountered during caesarean section (CS) in practice on mainly Belgian Blue (BB) cows and to identify the associated risk factors. Data were collected using a questionnaire completed by veterinarians of the Ambulatory Clinic of the Faculty of Veterinary Medicine, Ghent University (Belgium), immediately after performing a CS. Results revealed that the BB breed had fewer severe pre-operative problems than animals of other breeds, most probably due to the fact that CSs in this breed are performed in a very early stage of parturition. Mild as well as severe difficulties were more likely to happen during surgery in cows that had undergone a CS before. Cows at their second or third surgery had a significantly higher proportion of larger calves and more skin scar tissue was present, both increasing the risk of abdominal wall muscular and uterine haemorrhage. These factors can all lead to problems with exteriorization and suturing of the uterus; hence special attention is needed when performing a CS on a cow which has experienced the procedure before. The more experienced veterinarians were less likely to report difficulties during the operation than less experienced surgeons.

Preparation of fluorescence ethosomes based on quantum dots and their skin scar penetration properties

In this study, the fluorescence ethosomes (ES-QDs) composed of hydrophilic CdTe fluorescent clusters (quantum dots, QDs) were prepared. The prepared ES-QDs with even particle size were obtained by extruding the vesicles through polycarbonate membrane filters and were characterized by TEM SEM HPPS and photoluminescence spectra. Their in vitro experiments to penetrate into human skin scar were performed by using the Franz diffusion cell. Results showed that the prepared ES-QDs not only have the properties of ethosome to penetrate the skin scar tissues but also have the fluorescence labeling properties of the quantum dots. The prepared ES-QDs have potential clinical application in therapy of skin scar.

Peptide growth factors and myofibroblasts in capsules around human breast implants.

Peptide growth factors were mapped immunohistochemically for assessment of their presumed relation to the cells in capsules enveloping gel-filled, smooth-surfaced silicone mammary implants (12 capsules from 11 women). The implant capsules were dominated by fibroblast-like cells, but there were as well macrophages, inflammatory cells, and vascular cells. These cells expressed immunoreactivity for TGF-beta, IGF-II, IGF-I, and, to a lesser extent, PDGFB, NGF, and TNF-alpha. The numerous spindle-shaped cells in the contracted capsules displayed several distinct cytoplasmic actin bundles and fulfilled ultrastructural criteria for myofibroblasts. In contrast, myofibroblasts were recognized in low frequencies in the noncontracted capsules. Mature skin scar tissue did not show any peptide growth factor immunoreactivity, and myofibroblasts were absent. It is postulated that the low-grade chronic inflammatory foreign-body reaction, aggravated by mechanical stress and possible leakage of irritants, stimulates capsule cells to form peptide growth factors, reflecting that extended healing processes prevail in both noncontracted and contracted capsules. We propose that the local enrichment of peptide growth factors, beneficial for acute wound healing, in the chronically irritated tissue around implants provides trophic support for the contractile cells in the implant capsules.