Development Of Hypertrophic Scars Research Articles

Dissecting the association between gut microbiota and hypertrophic scarring: a bidirectional Mendelian randomization study.

Hypertrophic scars affect a significant number of individuals annually, giving rise to both cosmetic concerns and functional impairments. Prior research has established that an imbalance in the composition of gut microbes, termed microbial dysbiosis, can initiate the progression of various diseases through the intricate interplay between gut microbiota and the host. However, the precise nature of the causal link between gut microbiota and hypertrophic scarring remains uncertain. In this study, after compiling summary data from genome-wide association studies (GWAS) involving 418 instances of gut microbiota and hypertrophic scarring, we conducted a bidirectional Mendelian randomization (MR) to investigate the potential existence of a causal relationship between gut microbiota and the development of hypertrophic scar and to discern the directionality of causation. By utilizing MR analysis, we identified seven causal associations between gut microbiome and hypertrophic scarring, involving one positive and six negative causal directions. Among them, Intestinimonas, Ruminococcus2, Barnesiella, Dorea, Desulfovibrio piger, and Ruminococcus torques act as protective factors against hypertrophic scarring, while Eubacterium rectale suggests a potential role as a risk factor for hypertrophic scars. Additionally, sensitivity analyses of these results revealed no indications of heterogeneity or pleiotropy. The findings of our MR study suggest a potential causative link between gut microbiota and hypertrophic scarring, opening up new ways for future mechanistic research and the exploration of nanobiotechnology therapies for skin disorders.

The regulatory role of the apelin/APJ axis in scarring: Identification of upstream and downstream mechanisms

Scarring, a prevalent issue in clinical settings, is characterized by the excessive generation of extracellular matrix within the skin tissue. Among the numerous regulatory factors implicated in fibrosis across various organs, the apelin/APJ axis has emerged as a potential regulator of fibrosis. Given the shared attribute of heightened extracellular matrix production between organ fibrosis and scarring, we hypothesize that the apelin/APJ axis also plays a regulatory role in scar development. In this study, we examined the expression of apelin and APJ in scar tissue, normal skin, and fibroblasts derived from these tissues. We investigated the impact of the hypoxic microenvironment in scars on apelin/APJ expression to identify the transcription factors influencing apelin/APJ expression. Through overexpressing or knocking down apelin/APJ expression, we observed their effects on fibroblast secretion of extracellular matrix proteins. We further validated these effects in animal experiments while exploring the underlying mechanisms. Our findings demonstrated that the apelin/APJ axis is expressed in fibroblasts from keloid, hypertrophic scar, and normal skin. The regulation of apelin/APJ expression by the hypoxic environment in scars plays a significant role in hypertrophic scar and keloid development. This regulation promotes extracellular matrix secretion through upregulation of TGF-β1 expression via the PI3K/Akt/CREB1 pathway.

Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen.

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.

Perifascial areolar tissue graft promotes angiogenesis and wound healing in an exposed ischemic component rabbit model.

Multiple studies have reported the use of perifascial areolar tissue (PAT) grafts to treat wounds involving exposed ischemic tissues, avascular structures, and defective membrane structures. Our objective was to assess the quantitative effects of PAT grafts and their suitability for wounds with ischemic tissue exposure and to qualitatively determine the factors through which PAT promotes wound healing and repair. We conducted histological, immunohistochemical, and mass spectrometric analyses of the PAT grafts. PAT grafts contain numerous CD34+ progenitor/stem cells, extracellular matrix, growth factors, and cytokines that promote wound healing and angiogenesis. Furthermore, we established a male rabbit model to compare the efficacy of PAT grafting with that of an occlusive dressing treatment (control) for wounds with cartilage exposure. PAT grafts could cover ischemic components with granulation tissue and promote angiogenesis. Macroscopic and histological observations of the PAT graft on postoperative day seven revealed capillaries bridging the ischemic tissue (vascular bridging). Additionally, the PAT graft suppressed wound contraction and alpha smooth muscle actin (αSMA) levels and promoted epithelialization. These findings suggested that PAT can serve as a platform to enhance wound healing and promote angiogenesis. This is the first study to quantify the therapeutic efficacy of PAT grafts, revealing their high value for the treatment of wounds involving exposed ischemic structures. The effectiveness of PAT grafts can be attributed to two primary factors: vascular bridging and the provision of three essential elements (progenitor/stem cells, extracellular matrix molecules, and growth factors/cytokines). Moreover, PAT grafts may be used as transplant materials to mitigate excessive wound contraction and the development of hypertrophic scarring.

PTEN hinders the formation of scars by regulating the levels of proteins in the extracellular matrix and promoting the apoptosis of dermal fibroblasts through Bcl-xL

Hypertrophic scar (HS) is a dermatological condition characterized by an excessive accumulation of proteins in the extracellular matrix (ECM) and an elevated cell count. The development of HS is thought to be linked to the disruption of dermal fibroblast proliferation and apoptosis. The processes of cell proliferation and apoptosis are notably influenced by PTEN. However, the precise mechanisms by which PTEN regulates hypertrophic scar fibroblasts (HSFs) and its overall role in scar formation are still not fully understood. The objective of this study was to investigate the influence of PTEN on hypertrophic scars(HS) and its function in the regulation of scar formation, with the aim of identifying a pivotal molecular target for scar treatment. Our results demonstrate that the overexpression of PTEN (AdPTEN) significantly suppressed the expression of type I collagen (Col I), type III collagen (Col III), and alpha smooth muscle actin (α-SMA) in HSFs. Furthermore, it was observed that the introduction of AdPTEN resulted in the suppression of Bcl-xL expression, which consequently led to an increase in the apoptosis of HSFs. Similarly, in the inhibition of collagens expression and subsequent increase in HSF apoptosis were also observed upon silencing Bcl-xL (sibcl-xL). Additionally, the in vitro model demonstrated that both AdPTEN and sibcl-xL were effective in reducing the contraction of FPCL. The findings of our study provide validation for the role of PTEN in inhibiting the development of hypertrophic scars (HS) by modulating the expression of extracellular matrix (ECM) proteins and promoting apoptosis in hypertrophic scar fibroblasts (HSFs) via Bcl-xL. These results indicate that PTEN and Bcl-xL may hold promise as potential molecular targets for therapeutic interventions aimed at managing hypertrophic scars.

RIPK3 Expression in Fibroblasts in an in vivo and in vitro Skin Wound Model: A Controversial Result.

One of the major problems of regenerative medicine is the development of hypertrophic scars and keloids. The protein kinase RIPK3 is involved in necroptosis; however, recent evidence indicates that it also has non-canonical functions, including its involvement in the development of renal fibrosis. The aim of our work was to study the expression of RIPK3 in mouse and human skin models of fibrotic processes. A subpopulation of RIPK3+Vim+ cells was found in both human keloid and a mouse wound, with the cell number being significantly greater in the mouse wound bed compared to healthy skin. Real-time polymerase chain reaction (RT-PCR) detected expression of the Ripk3 and fibroblast biomarkers Acta2, Fap, Col1a1, and Fn1 in the cells isolated from the wound bed, indicating that RIPK3 can be expressed by wound bed fibroblasts. An analysis of the human fibroblasts stained with anti-RIPK3 antibodies demonstrated an increase in the fluorescence intensity in the presence of lipopolysaccharide (LPS) at concentrations of 5, 10, 25, 50, and 100 ng/ml and TGF-β at concentrations of 0.1, 1, 2, and 5 ng/ml compared to the control. At the same time, the expression levels of RIPK3 and fibroblast activation markers in the presence of TGF-β and LPS did not differ significantly from the control. It is possible that RIPK3 expression in wound fibroblasts is not directly associated with fibrotic processes, and that kinase plays a different, yet unknown role in wound healing. KEYWORDS scarring, keloid, skin, fibroblasts, cell culture, RIPK3.

Comparing the Effectiveness of Glucocorticoids in Preventing Hypertrophic Scar Diagnosis in Burn Patients.

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

A novel combined technology for treating hypertrophic scars: adipose tissue extract combined with fractional CO2 laser.

Introduction: Owing to the need for liposuction and its unsuitability for allogeneic transplantation, the clinical application of stromal vascular fraction gel (SVF-gel) combined with fractional CO2 laser for scar treatment is limited. Adipose tissue extract (ATE), rich in cytokines and growth factors, offers a more convenient option for clinical practice as it can be easily prepared using purely physical methods and has low immunogenicity. We aimed to evaluate the effectiveness of ATE combined with fractional CO2 laser in the treatment of hypertrophic scars. Methods: ATE was prepared using discarded liposuction fluid from patients undergoing liposuction. A rabbit ear hypertrophic scar model was established and treated with ATE, fractional CO2 laser, or a combination. PBS was used as a control. The scar appearance and histological changes were observed. The immunohistochemistry method was used to evaluate the expression of α-SMA, while perilipin was detected using immunofluorescence. Additionally, the level of adipogenic signal C/EBPα and PPARγ mRNA was studied. Results: Following treatment, the volume of hypertrophic scar decreased, resulting in a softer texture and thinner dermis. Additionally, there was a decrease in the infiltration of inflammatory cells, and the collagen arrangement became looser and more regular, and the expression of α-SMA also decreased, with the combination of ATE and fractional laser showing the most significant improvement. Moreover, the combination group was found to promote subcutaneous fat regeneration and increase the expression of adipogenic signals C/EBPα and PPARγ. Conclusion: The combination of ATE and fractional CO2 laser treatment has been shown to inhibit the development of hypertrophic scars. This effect may be attributed to the enhancement of adipogenesis and decrease in collagen deposition.

The effects of Shikonin on the hypertrophic scar of rabbit ears via the TLR4/NF-κB signaling pathway.

As a traditional Chinese medicine, Zihuang Shengji Ointment has obvious effects on promoting postoperative wound healing and reducing scar formation in clinical application. Shikonin is the major phytochemical in Zihuang Shengji Ointment. As a kind of naphquinone compound with anti-tumor, anti-viral, anti-inflammatory, anti-bacterial and other biological activities extracted from Lithospermum erythrorhizon, shikonin exerts an important role in many diseases. Shikonin has impacts on the development of hypertrophic scars (HS), however, these effects are yet mostly unknown. As a result, we created the Newland white rabbit ear HS model, administered shikonin to it, and then assessed scar hypertrophy using HE and VG staining. The degree of scarring is assessed by HI, NA, as well as AA. The expression levels of collagen I, collagen III, as well as α-SMA as well as fibroblast proliferation, are also measured using real-time PCR, immunohistochemistry, and western blot. TUNEL tests are used to assess fibroblast apoptosis. In our work, HE staining and VG staining showed that the shikonin-treated group had normal bundles of collagen fibers and regular fibroblasts. Shikonin suppresses the production of HS, according to histopathological features, HI, NA, and AA measures. Shikonin also causes fibroblast apoptosis and lowers the production of α-SMA, collagen I, as well as collagen III in the HS rat. Notably, we discover that NF-κB activation and TLR4 activity are inhibited by shikonin. Overall, the results show that the signaling pathway of TLR4/NF-κB is modulated by shikonin's inhibitory effect on scar formation, which represses the levels of collagen I, collagen III, α-SMA, as well as fibroblasts.

The role of matrix metalloproteinases and their tissue inhibitors in the formation of hypertrophic skin scars with the use of a pulsed dye laser and Fermencol phonophoresis

BACKGROUND: An imbalance between matrix metalloproteinases (MMPs) expression and tissue inhibitors of MMP is considered as a possible mechanism for impaired collagen synthesis and degradation, which leads to the development of hypertrophic scars. The use of a vascular laser, in particular a pulsed dye laser, leads to coagulation of the vascular locus that feeds the hypertrophic skin scar, resulting in a decrease in extracellular matrix synthesis. The use of collagenase phonophoresis increases the effectiveness of laser therapy due to the destruction of the extracellular matrix.
 AIM: To study the role of matrix metalloproteinases and their tissue inhibitors in the pathogenesis of immature hypertrophic skin scars and to evaluate the dynamics of enzymes during the combined use of a pulsed dye laser and Fermenkol phonophoresis.
 MATERIAL AND METHODS: The study was performed with the participation of 125 patients aged 22 to 55 years with immature (up to 6 months) hypertrophic skin scars. All patients were divided into 4 groups according to the simple fixed randomization procedure. The first group (control, n=32) received course local compression therapy using silicone plates for 2 months. The second group (main group I, n=31) underwent two courses of Fermencol phonophoresis (5 daily procedures lasting 10 minutes each with a break of 34 weeks). The third group (main group II, n=31) underwent two pulsed dye laser procedures with an interval of 4 weeks. The fourth group (main III, n=31) received complex treatment, which included a combination of two pulsed dye laser procedures and two cycles of Fermenkol phonophoresis. The study of the clinical condition of patients was carried out according to the modified Vancouver scar scale (VSS). The content of MMP and tissue inhibitor of metalloproteinase-1 in blood serum was determined by enzyme immunoassay. Patients were examined twice: before the start and 2 weeks after the end of the course of treatment. To form a sample of reference values of MMPs and tissue inhibitors of metalloproteinases (TIMPs), a group of 20 somatically healthy individuals was used.
 RESULTS: Initially reduced levels of MMP-1 and MMP-9 were found in the blood serum of patients with immature hypertrophic skin scars, with high values of TIMP-1, which allows us to consider reduced expression as an important link in the pathogenesis of the fibroproliferative process in the skin, which causes excessive deposition of extracellular matrix components. The use of pulsed dye laser in combination with Fermencol phonophoresis was accompanied by an increase in the content of MMP in the blood serum of patients with immature hypertrophic skin scars, which positively correlated with the severity of the clinical result of treatment, assessed by VSS.
 CONCLUSION: A conclusion was made about the clinical and pathogenetic significance of MMPs and TIMPs in the development of fibroplastic processes, which allows us to consider these biochemical parameters as informative criteria for the effectiveness of the therapy.

Deciphering the contributions of cuproptosis in the development of hypertrophic scar using single-cell analysis and machine learning techniques.

Hypertrophic scar (HS) is a chronic inflammatory skin disease characterized by excessive deposition of extracellular matrix, but the exact mechanisms related to its formation remain unclear, making it difficult to treat. This study aimed to investigate the potential role of cuproptosis in the information of HS. To this end, we used single-cell sequencing and bulk transcriptome data, and screened for cuproptosis-related genes (CRGs) using differential gene analysis and machine learning algorithms (random forest and support vector machine). Through this process, we identified a group of genes, including ATP7A, ULK1, and MTF1, as novel therapeutic targets for HS. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to confirm the mRNA expression of ATP7A, ULK1, and MTF1 in both HS and normal skin (NS) tissues. We also constructed a diagnostic model for HS and analyzed the immune infiltration characteristics. Additionally, we used the expression profiles of CRGs to perform subgroup analysis of HS. We focused mainly on fibroblasts in the transcriptional profile at single-cell resolution. By calculating the cuproptosis activity of each fibroblast, we found that cuproptosis activity of normal skin fibroblasts increased, providing further insights into the pathogenesis of HS. We also analyzed the cell communication network and transcription factor regulatory network activity, and found the existence of a fibroblast-centered communication regulation network in HS, where cuproptosis activity in fibroblasts affects intercellular communication. Using transcription factor regulatory activity network analysis, we obtained highly active transcription factors, and correlation analysis with CRGs suggested that CRGs may serve as potential target genes for transcription factors. Overall, our study provides new insights into the pathophysiological mechanisms of HS, which may inspire new ideas for the diagnosis and treatment.

Serum Amyloid P Attenuates Hypertrophic Scarring in Large Animal Models

IntroductionThis study's purpose was to (1)determine the effect of locally administered serum amyloid P (SAP) on the development of hypertrophic scars (HTS) in porcine and rabbit HTS models and (2)determine the pharmacokinetics of systemically administered SAP and its effect on circulating fibrocyte quantities. MethodsTwo large animal (New Zealand White Rabbit and Female Red Duroc Pigs) HTS models were utilized to study the effects of daily local injections of SAP immediately post wounding (x5 d in rabbits; x7 d in pigs) on HTS development as measured by scar elevation index , scar area, wound closure, and molecular expression studies of scar components. For SAP pharmacokinetics, total and human SAP levels in porcine blood were measured at regular intervals following intravenous administration of human SAP. Fibrocyte quantities were determined prior to and 1 h following human SAP intravenous administration. ResultsIn the rabbit model, local SAP significantly decreased the level of tissue inhibitor of metalloproteinases-1 mRNA expression and maintained matrix mettaloproteinase-9 expression, while control and vehicle groups significantly declined. In the pig model, there was a significant decrease in the trend of scar elevation indexes treated with local SAP versus controls over the study period. This decrease was statistically significant at days 14 and 84. Human SAP administered intravenously is degraded within 24 h and does not influence circulating fibrocyte quantities. ConclusionsThis is the first study to demonstrate attenuation of HTS formation using locally administered SAP in large animal HTS models. Local SAP administration reduces HTS formation by maintaining matrix mettaloproteinase-9 and decreasing tissue inhibitor of metalloproteinases-1. Intravenous administration of SAP is not as effective.

Children's post-burn scars in Mongolia.

This study aimed to identify some risk factors for post-burn scarring in children aged 0-18 years. One hundred and eighty two participants were involved in this cohort study. Under the age of 18 who were admitted to the Department of Burn Reconstructive Surgery with a diagnosis of upper and lower extremity burns were followed for 6months. A total of 182 participants (62.1% male, and 37.9% female participants) enrolled in this study. Age ranged from 1 to 17 and the average age was 3.95 ± 3.35. The degree of burn and the anatomical location of the burn had a statistically significant effect on the development of hypertrophic scars. The length of the patient's hospitalisation days and the area of ​​the burn were statistically correlated with wound healing (P= 000, P= .074). For example, the average length of hospitalisation days was 8± 5 days in the hypertrophic scars group of patients, and in the group with normal scars, average bed days were 6± 3 days (P= .000). Grade IIIb burns increased the risk of hypertrophic scar development by 4.9 times and grade IV burns increased it by 2.5 times. In addition, when the area of burns was 11% or more, the risk of hypertrophic scar development was increased by 58.8%. In the case of wound swab infection, the risk of hypertrophic scar development was 12.4% higher (B= 1.124, 95 EI=0.55; 2.28, P= .748). Participants' age, burn area and degree of burn are statistically significant risk factors for post-burn scarring in children aged 0-18 years.

Evaluating the effects of botulinum toxins to minimize post cleft lip hypertrophic scar

Abstract:
 
 Background: Cleft lip deformity is one of the most common congenital anomalies. Repair of cleft lip may create too much tension especially when done in wide cleft lip, and this may result in unacceptable scar.
 
 Aim of study: To evaluate the efficacy of botulinum toxin in reducing or preventing post cheiloplasty hypertrophic scar.
 
 Patient and method: Between the period from October 2019 to August 2021, 10 patients with cleft lip were subjected to primary cheiloplasty using Millard rotation advancement flap technique followed by botulinum toxin injection into the site of repair. Follow up period was 6 months postoperatively.
 
 Results: All of our patients showed excellent result which was evaluated using visual analogue scale assessment which was done by tow independent surgeons. Our patients showed barely visible scar at 6 months postoperatively with no recorded hypertrophic scar. No side effect was recorded related to botulinum toxin injection.
 
 Conclusion: Botulinum toxin injection after primary cheiloplsty showed to be safe and effective in prevention of development of unacceptable hypertrophic scar.
 
 
 Keywards: botulinum, cleft lip, hypertrophic scar, cheiloplasty.

Platycodin D inhibits the proliferation and migration of hypertrophic scar-derived fibroblasts and promotes apoptosis through a caspase-dependent pathway

Abnormal fibroblast proliferation and excessive extracellular matrix (ECM) deposition lead to the formation of hypertrophic scars (HSs). However, there is no satisfactory method to inhibit the occurrence and development of HSs. In our study, platycodin D (PD), a natural compound extracted from Platycodon grandiflorus, inhibited HSs formation both in vitro and in vivo. First, qRT-PCR and Western blot were used to confirm PD dose-dependently downregulated the expression of Col I, Col III and α-SMA in human hypertrophic scar-derived fibroblasts (HSFs) (p < 0.05). Second, cck-8, transwell and wound healing assays verified PD suppressed the proliferation (p < 0.05) and migration of HSFs (p < 0.05), and inhibited the differentiation of HSFs into myofibroblasts. Moreover, PD-induced HSFs apoptosis were analyzed by flow cytometry and the apoptosis was activated through a caspase-dependent pathway. The rabbit ear scar model was used to further confirm the inhibitory effect of PD on collagen and α-SMA deposition. Finally, Western blot analysis showed that PD reduced TGF-β RI expression (p < 0.05) and affected matrix metalloproteinase 2 (MMP2) protein levels (p < 0.05). In conclusion, our study showed that PD inhibited the proliferation and migration of HSFs by inhibiting fibrosis-related molecules and promoting apoptosis via a caspase-dependent pathway. The TGF-β/Smad pathway also mediated the inhibition of HSFs proliferation and HSFs differentiation into myofibroblasts. Therefore, PD is a potential therapeutic agent for HSs and other fibrotic diseases.

The histopathological and phenotypic characteristics of keloid and hypertrophic scar during wound closure with compressive and non-compressive sutures

Keloids and hypertrophic scars are fibroproliferative disorders caused by abnormal wound healing. They extend beyond the borders of the primary wound, do not regress spontaneously, and tend to recur after excision. Every year in developed countries, about 100 million people face problems related to scars. Hypertrophied scars and keloids have a significant impact on the patient's quality of life, physical condition and psychological health. Compression sutures are traditionally used for wound closure in clinical practice. Compression sutures mean regular sutures, which are used to close the wound with a knotted suture, which causes tissue compression. Non-compressive sutures are sutures of ordinary composition treated with a unique technology, which have a tufted structure, and at the expense of these tufts, they close the wound without forming knots. In case of their use, the histopathological and phenotypic features of the development of keloids and skin scars compared to compressive threads require more research. In histopathological practice, the histopathological indicators that will allow us to determine the high and low risk groups for the development of keloids and hypertrophic scars are still not well studied; Which may have a great clinical value because it allowed us to identify the high and low risk of possible development of keloid based on Punch-biopsy. The complex mechanisms of keloid formation are still unknown and probably depend on the body's ability to respond to damage on the one hand and environmental factors, including the use of compression threads, on the other hand.

Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts

Post-burn hypertrophic scars are characterized by excessive accumulation of extracellular matrix secreted by fibroblasts. Exosomes are membrane lipid extracellular vesicles that play a pivotal role in cellular communication. Previous studies revealed the role of stem cell-derived exosomes in repairing damaged tissues, and also showed that cancer cell-derived exosomes could affect the disease pathogenesis. However, the functional properties of exosomes derived from hypertrophic scar fibroblasts (HTSFs) have not yet been studied extensively. In this study, we aimed to investigate whether HTSFs-derived exosomes can change the fibrosis-related signaling pathways in human normal fibroblasts (HNFs). HTSFs and HNFs were isolated from human hypertrophic scar tissues. HTSFs-derived exosomes were extracted and treated to HNFs. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect mRNA and protein expression, respectively, and cell proliferation and mobility were also assessed. Exosome treatment markedly increased cell proliferation and migration, and induced small mother against decapentaplegic (SMAD) signaling by increasing the levels of phosphorylated SMAD2 and SMAD1/5/8. The levels of TAK1 signaling components were also increased after exosome treatment to HNFs, including phosphorylated TAK1, p38, ERK, and JNK. HTSFs-derived exosomes further induced the epithelial-mesenchymal transition by decreasing the expression level of E-cadherin and increasing the expression levels of N-cadherin and vimentin. Consequently, the expression levels of fibronectin, type Ⅰ collagen, and type Ⅲ collagen were increased. Our results demonstrate the fibrotic property of HTSFs-derived exosomes, which suggests a potential functional role in hypertrophic scar development and a new therapeutic target.

Roles of cutaneous cell-cell communication in wound healing outcome: An emphasis on keratinocyte-fibroblast crosstalk.

Tissue repair is a very complex event and involves a continuously orchestrated sequence of signals and responses from platelets, fibroblasts, epithelial, endothelial and immune cells. The details of interaction between these signals, which are mainly growth factors and cytokines, have been widely discussed. However, it is still not clear how activated cells at wound sites lessen their activities after epithelialization is completed. Termination of the wound healing process requires a fine balance between extracellular matrix (ECM) deposition and degradation. Maintaining this balance requires highly accurate epithelial-mesenchymal communication and correct information exchange between keratinocytes and fibroblasts. As it has been reported in the literature, a disruption in epithelialization during the process of wound healing increases the frequency of developing chronic wounds or fibrotic conditions, as seen in a variety of clinical cases. Conversely, the potential stop signal for wound healing should have a regulatory role on both ECM synthesis and degradation to reach a successful wound healing outcome. This review briefly describes the potential roles of growth factors and cytokines in controlling the early phase of wound healing and predominantly explores the role of releasable factors from epithelial-mesenchymal interaction in controlling during and the late stage of the healing process. Emphasis will be given on the crosstalk between keratinocytes and fibroblasts in ECM modulation and the healing outcome following a brief discussion of the wound healing initiation mechanism. In particular, we will review the termination of acute dermal wound healing, which frequently leads to the development of hypertrophic scarring.

Comparison of Thermal Burn-Induced and Excisional-Induced Scarring in Animal Models: A Review of the Literature.

Significance: Scar formation is a natural result of mammalian wound healing. In humans and other mammals, however, deep dermal wounds and thermal injuries often result in formation of hypertrophic scars, leading to substantial morbidity and lending great importance to development of therapeutic modalities for burn scars. Clinical Issues: Thus, preclinical burn wound models that adequately simulate processes underlying human burn-induced wound healing, particularly those processes leading to chronic inflammation and development of hypertrophic scars, are critical to developing further treatment paradigms for clinical use. Approach: In this study, we review literature describing various burn models, focusing on their characteristics and the functional readouts that lead to generation of useful data. We also briefly discuss recent work using human ex vivo skin culture as an alternative to animal models, as well as our own development of rabbit ear wound models for burn scars, and assess the pros and cons of these models compared to other models. Future Direction: Understanding of the strengths and weaknesses of preclinical burn wound models will enable choice of the most appropriate wound model to answer particular clinically relevant questions, furthering research aimed at treating burn scars.

LncRNA PAPPA-AS1 Induces the Development of Hypertrophic Scar by Upregulating TLR4 through Interacting with TAF15.

Hypertrophic scar (HTS) is a complicated pathological process induced mainly by burns and wounds, with abnormal proliferation of fibroblasts and the transformation of fibroblasts to myofibroblasts. PAPPA-AS1, a differentially expressed long noncoding RNA (lncRNA) in the HTS tissues, attracted our interests in its potential role and mechanism in the development and process of HTS. In the present study, the regulatory effect of lncRNA PAPPA-AS1 on the Toll-like receptor 4 (TLR4) signal pathway, as well as the molecular mechanism, was investigated. Bioinformatics analysis was utilized to screen the differentially expressed lncRNAs in HTS tissues. PAPPA-AS1 was significantly upregulated in both HTS tissues and hypertrophic scar fibroblast (HTsFb) cells. The expression levels of TLR4, MyD88, TGF-β1, collagen I, collagen III, and α-SMA were greatly elevated in HTsFb cells. By knocking down PAPPA-AS1, the proliferation of HTsFb cells, TLR4, and TGF-β1 signal pathway and the expression of fibrosis markers both in HTsFb cells and HTS tissues were suppressed. It was accompanied by the alleviated pathological state in the HTS tissues, which were significantly reversed by cotransfecting with the pcDNA3.1-TLR4 vector. Positive correlation and interaction were observed between PAPPA-AS1 and TAF15 and between TAF15 and the promoter of TLR4, respectively. In conclusion, lncRNA PAPPA-AS1 might induce the development of HTS by upregulating TLR4 through interacting with TAF15.