Pathological Scars Research Articles

Design of an Innovative Method for Measuring the Contractile Behavior of Engineered Tissues.

Hypertrophic scarring is a common complication in severely burned patients who undergo autologous skin grafting. Meshed skin grafts tend to contract during wound healing, increasing the risk of pathological scarring. Although various technologies have been used to study cellular contraction, current methods for measuring contractile forces at the tissue level are limited and do not replicate the complexity of native tissues. Self-assembled skin substitutes (SASSs) were developed at the "Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX" and are used as permanent full-thickness skin grafts. The autologous skin substitutes are produced using the self-assembly method, allowing the cultured cells to produce their extracellular matrix leading to a tissue-engineered substitute resembling the native skin. The level of contraction of the SASSs during the fabrication process is patient-dependent. Thus, because of its architecture and composition, SASS is an interesting model to study skin contraction in vitro. Unfortunately, standard measurement methods are unsuited for SASS contraction assessment, mainly due to incompatibilities between the SASS manufacturing process and the current contraction force measurement methods. Here, we present an innovative contraction measurement method specifically designed to quantify the contractile behavior of tissue-engineered substitutes, without disrupting the protocol of production. The method uses C-shape anchoring frames that close at different speeds and magnitudes according to the tissue contractile behavior. A finite element analysis model is then used to associate the frame deformation to a contractile force amplitude. This article shows that the method can be used to measure the contraction force of tissues produced with cells displaying different contractile properties, such as primary skin fibroblasts and myofibroblasts. It can also be used to study the effects of cell culture conditions on tissue contraction, such as serum concentration. This protocol can be easily and affordably applied and tuned to many regenerative medicine applications or contraction-related pathological studies. Impact Statement The protocol presented in this article is a new and simple method to quantify contraction forces present in tissue-engineered substitutes. Using finite element analysis, it allows for the measurement of a contraction force rather than a surface reduction as usually provided by other tissue contraction measurement methods. The results shown are in correlation with the current literature relevant to tissue contraction. It can be easily implemented, and hence, this method will open up new avenues to study tissue contraction of living substitutes engineered with various cell types and to optimize culture conditions.

The Role of Biomechanical Forces in the Formation and Treatment of Pathological Scars

The Role of Biomechanical Forces in the Formation and Treatment of Pathological Scars

Current Management of Pediatric Patients with Post-Burn Scars: Case Study

Background. Post-burn scars are common among pediatric patients. Pathological scarring is clear indication for conservative or surgical management of pediatric patients who continue to grow and develop after the resolution of burn injuries. Such lesions can significantly reduce patients' quality of life and, moreover, cause significant functional and aesthetic discomfort. Clinical cases description. The results of observation over two children (2 years 7 months and 12 years) with developing post-burn scars are demonstrated. Successful management method using physiotherapeutic complex (including monopolar radiofrequency treatment combined with ultrasound therapy, photodynamic therapy, and close-focus X-ray therapy) is presented. Conclusion. Modern trends in post-burn scars management are based on timely implementation of effective and safe methods early on rehabilitation stages and tissue restoration after burn injury to prevent pathological scarring and achieve control over its activity.

An Update on Molecular Mechanisms of Scarring-A Narrative Review.

Fibroblasts, the principal cellular mediators of connective tissue remodeling, play a crucial role in the formation of physiological and pathological scars. Understanding the intricate interplay between fibroblasts and other cellular and molecular components is essential for elucidating the underlying mechanisms driving scar formation. Hypertrophic scars, keloids and atrophic scars arise from dysregulated wound healing processes characterized by persistent inflammation, aberrant collagen deposition, and impaired extracellular matrix remodeling. Fibroblasts play a central role in the pathogenesis of such pathological scars, driving aberrant extracellular matrix remodeling, subsequently contributing to the formation of raised or depressed fibrotic lesions. The investigation of complex interactions between fibroblasts and the microenvironment is crucial for developing targeted therapeutic interventions aimed at modulating fibroblast activity and improving clinical outcomes in patients with pathological scars. Further research into the molecular pathways governing fibroblast behavior and their heterogeneity holds promise for advancing scar management strategies. This narrative review was performed to shed light on the mechanisms behind scar formation, with a special focus on the role of fibroblasts in the formation of different types of scars, providing insights into the pathophysiology of these conditions. Through the analysis of current knowledge, this review seeks to identify the key cellular and molecular mechanisms involved in fibroblast activation, collagen synthesis, and extracellular matrix remodeling in hypertrophic scar, keloid, or atrophic scar formation.

The Role of Extracorporeal Shock Wave Therapy in Keloids and Hypertrophic Scars: A Systematic Review.

Keloids and hypertrophic scars are pathological scars that result from a prolonged and aberrant response to wound healing, resulting in raised and thickened skin lesions. Traditional treatments include occlusive dressings, compression therapy, intralesional steroids, and surgical excision with refashioning. Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment method that employs mechanotransduction to stimulate a biological cascade resulting in tissue regeneration. This review aims to explore the literature for published evidence on the role of ESWT in the treatment of keloids and hypertrophic scars. A literature search following the PRISMA guidelines was conducted on PUBMED, Google Scholar, and the Cochrane Database of Systematic Reviews, for studies demonstrating the use of ESWT in keloids and hypertrophic scars. From this, 79 articles were identified, 12 of which met the eligibility criteria and were thus analyzed and included in the study. As monotherapy for keloids, ESWT showed comparable improvements in functional and aesthetic outcomes compared to traditional intralesional steroid therapy. Keloids treated with combination therapy of ESWT with intralesional steroids had better outcomes than those treated with intralesional steroids alone. Improvements in hypertrophic scar cosmesis, discomfort, and function with the use of ESWT were reported. Histologic improvements such as decreased collagen content, reduction of fibrotic markers, and fibrogenic cytokines were also described. ESWT is a promising treatment modality for pathological scars, offering comparable outcomes to traditional therapies with added benefits such as non-invasiveness. Further research is warranted to establish optimal protocols and its role in pathological scar management.

Characterization and Physiological Differences of Two Primary Cultures of Human Normal and Hypertrophic Scar Dermal Fibroblasts: A Pilot Study.

Background/Objectives: Dermal fibroblasts (DFs) are key participants in skin hypertrophic scarring, and their properties are being studied to identify the molecular and cellular mechanisms underlying the pathogenesis of skin scarring. Methods: In the present work, we performed a comparative analysis of DFs isolated from normal skin (normal dermal fibroblasts, NDFs), and hypertrophic scar skin (hypertrophic scar fibroblasts, HTSFs). The fibroblasts were karyotyped and phenotyped, and experiments on growth rate, wound healing, and single-cell motility were conducted. Results: Comparative analysis revealed a minor karyotype difference between cells. However, HTSFs are characterized by higher proliferation level and motility compared to NDFs. These significant differences may be associated with quantitative and qualitative differences in the cell secretome. A proteomic comparison of NDF and HTSF found that differences were associated with metabolic proteins reflecting physiological differences between the two cells lines. Numerous unique proteins were found only in the vesicular phase of vHTSFs. Some proteins involved in cell proliferation (protein-glutamine gamma-glutamyltransferase K) and cell motility (catenin delta-1), which regulate gene transcription and the activity of Rho family GTPases and downstream cytoskeletal dynamics, were identified. A number of proteins which potentially play a role in fibrosis and inflammation (mucin-5B, CD97, adhesion G protein-coupled receptor E2, antileukoproteinase, protein S100-A8 and S100-A9, protein caspase recruitment domain-containing protein 14) were detected in vHTSFs. Conclusions: A comparative analysis of primary cell cultures revealed their various properties, especially in the cell secretome. These proteins may be considered promising target molecules for developing treatment or prevention strategies for pathological skin scarring.

Efficacy of Hydrogen Sulfide Baths in Complex Burn Rehabilitation: a Single-Center Observational Study

INTRODUCTION. The healing of burn wounds often leads to pathological scars and scar contractures, significantly deteriorating the quality of life for patients who have experienced burn trauma. In comprehensive anti-scar therapy, balneotherapy with sulfide (hydrogen sulfide) waters can be applied alongside primary methods. However, due to a lack of modern information on its effectiveness, this method is not frequently included in rehabilitation programs. AIM. To determine the significance of hydrogen sulfide baths in comprehensive rehabilitation and improve treatment outcomes for patients with hypertrophic post-burn scars. MATERIALS AND METHODS. In the years 2021–2022, 110 patients, including adults and children, participated in an observational study at the Matsesta Balneological Resort (Sochi, Russia) titled “Evaluation of the Effectiveness of Balneotherapy for Post-Burn Scars in Adults and Children”. All patients received a course of 10 hydrogen sulfide irrigations or baths at the Matsesta Balneological Resort. Before the start of the procedure and after completion, scar tissue assessment using the Vancouver Scar Scale and patient surveys were conducted by a physiotherapist. RESULTS AND DISCUSSION. Among the patients, there were 40 adults and 60 children. The age of patients ranged from 2 to 61 years, with an average of 19.8 years; 49 were male, and 51 were female. The burn area in patients ranged from 5 to 90 % (average 33.1 %) of the body surface. After the first course of sulfide irrigations, the scar tissue assessment on the Vancouver Scar Scale decreased by 2.1 points in children and 2.2 points in adults. After a repeat course of sulfide irrigations, scar tissue assessment decreased by 1.3 points in children and 1.8 points in adults. According to surveys based on the Dermatology Life Quality Index, before treatment, patients subjectively rated their condition on average at 3.45 points, and after treatment, at an average of 2.76 points. The decrease in scores was mainly due to the reduction or disappearance of symptoms such as dryness, burning, pain, and paresthesia in the scar. CONCLUSION. Balneotherapy with sulfide waters for patients with hypertrophic post-burn scars within the first 24 months after burn trauma is effective for both children and adults.

Future Directions About Keloid Scars Based on Pathogenesis and Therapies.

Keloids are pathologic scars that pose a significant functional and cosmetic burden. While the literature on keloid management continues to expand, the absence of standardized guidelines or treatment protocols endorsed by academic governing bodies remains a significant challenge. The pathogenesis of keloid scars is not fully elucidated. This review delves into the intricate pathogenesis of keloids, exploring the molecular and cellular mechanisms underlying their formation. Conventional therapies are analyzed in-depth considering their efficacy and limitations, including surgical excision, pharmacotherapies, radiotherapy, cryotherapy, silicone-based product, pressure therapy, and light-based therapy. The emergence of novel therapeutic approaches is discussed, including pharmacotherapies, physical therapies, and biological therapies, shedding light on their potential in treating keloid scars. We also contemplate future directions in the field, encompassing the application of targeted therapies, gene-editing tools, tissue engineering, and regenerative medicine, together with psychosocial support and patient education. In synthesizing current knowledge, scrutinizing therapeutic modalities, and envisioning future avenues, this review aims to provide a comprehensive reference for clinicians, researchers, and stakeholders engaged in the intricate field of keloid management.

Cytokine priming enhances the antifibrotic effects of human adipose derived mesenchymal stromal cells conditioned medium

BackgroundFibrosis is a pathological scarring process characterized by persistent myofibroblast activation with excessive accumulation of extracellular matrix (ECM). Fibrotic disorders represent an increasing burden of disease-associated morbidity and mortality worldwide for which there are limited therapeutic options. Reversing fibrosis requires the elimination of myofibroblasts, remodeling of the ECM, and regeneration of functional tissue. Multipotent mesenchymal stromal cells (MSC) have antifibrotic properties mediated by secreted factors present in their conditioned medium (MSC-CM). However, there are no standardized in vitro assays to predict the antifibrotic effects of human MSC. As a result, we lack evidence on the effect of cytokine priming on MSC’s antifibrotic effects. We hypothesize that the MSC-CM promotes fibrosis resolution in vitro and that this effect is enhanced following MSC cytokine priming.MethodsWe compared the antifibrotic effects of resting versus interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) primed MSC-CM in four in vitro assays: prevention of fibroblast activation, myofibroblasts deactivation, ECM degradation and fibrosis resolution in lung explant cultures. Furthermore, we performed transcriptomic analysis of myofibroblasts treated or not with resting or primed MSC-CM and proteomic characterization of resting and primed MSC-CM.ResultsWe isolated MSC from adipose tissue of 8 donors, generated MSC-CM and tested each MSC-CM independently. We report that MSC-CM treatment prevented TGF-β induced fibroblast activation to a similar extent as nintedanib but, in contrast to nintedanib, MSC-CM reduced fibrogenic myofibroblasts (i.e. transcriptomic upregulation of apoptosis, senescence, and inflammatory pathways). These effects were larger when primed rather than resting MSC-CM were used. Priming increased the ability of MSC-CM to remodel the ECM, reducing its content of collagen I and fibronectin, and reduced the fibrotic load in TGF-β treated lung explant cultures. Priming increased the following antifibrotic proteins in MSC-CM: DKK1, MMP-1, MMP-3, follistatin and cathepsin S. Inhibition of DKK1 reduced the antifibrotic effects of MSC-CM.ConclusionsIn vitro, MSC-CM promote fibrosis resolution, an effect enhanced following MSC cytokine priming. Specifically, MSC-CM reduces fibrogenic myofibroblasts through apoptosis, senescence, and by enhancing ECM degradation. Future studies will establish the in vivo relevance of MSC priming to fibrosis resolution.

New challenges in scar therapy: the novel scar therapy strategies based on nanotechnology.

The pathological mechanism of pathological scar is highly complex, encompassing the abnormalities of diverse cytokines, signaling pathways and regulatory factors. To discover more preferable scar treatment options, a variety of distinct approaches have been utilized clinically. Nevertheless, these treatments possess certain side effects and are inclined to relapse. Presently, pathological scar treatment remains a clinical conundrum, and there is an urgent demand for treatment methods that are safe, less traumatic and have lower recurrence rates. New drug delivery systems, novel therapeutic drugs and therapy strategies can enable drugs to permeate the skin effectively, decrease side effects, enhance drug efficacy and even achieve pain-free self-administration. Currently, novel nanotechnologies such as nanomicroneedles, photodynamics mediated by novel photosensitizers, bioelectrical stimulation and 3D printed dressings have been developed for the effective treatment of pathological scars. Additionally, innovative nanoscale fillers, including nano-fat and engineered exosomes, can serve as novel therapeutic agents for the efficient treatment of pathological scars. The intervention of nanomaterials can enhance drug absorption, stabilize and safeguard the active ingredients of drugs, delay or control drug release and enhance bioavailability. This article reviews these new treatment strategies for scar to explore novel approaches for efficient and safe for keloid treatment.

Single-cell sequencing analysis and bulk-seq identify IGFBP6 and TNFAIP6 as novel differential diagnosis markers for postburn pathological scarring

BackgroundIf not accurately diagnosed and treated, postburn pathological scars, such as keloids and hypertrophic scars, can lead to negative clinical outcomes. However, differential diagnosis at the molecular level for postburn pathological scars remains limited. Using single-cell sequencing analysis, we investigated the genetic nuances of pathological scars at the cellular level. This study aimed to identify molecular diagnostic biomarkers to distinguish between postburn keloids and hypertrophic scars. MethodsSingle-cell sequencing, differential expression, and weighted co-expression network analyses were performed to identify potential key genes for discriminating between keloids and hypertrophic scars. Postburn clinical samples were collected from our centre to validate the expression levels of the identified key genes. ResultsSingle-cell sequencing analysis unveiled 29 and 30 cell clusters in keloids and hypertrophic scars, respectively, predominantly composed of fibroblasts. Bulk differential gene analysis showed 96 highly expressed genes and 69 lowly expressed genes in keloids compared to hypertrophic scars. By incorporating previous research, Gene Set Enrichment Analysis was conducted to select fibroblasts as the focus of research. According to the single-cell data, 301 genes were stably expressed in fibroblasts from both types of pathological scars. Consistently, Weighted Gene Co-expression Network Analysis revealed that the blue module genes were mostly hub genes associated with fibroblasts. After intersecting fibroblast-related genes in single-cell data, Weighted Gene Co-expression Network Analysis-hub module genes, and bulk differential expression genes, insulin-like growth factor binding protein 6 and tumour necrosis factor alpha-induced protein 6 were identified as key genes to distinguish keloids from hypertrophic scars, resulting in diagnostic accuracies of 1.0 and 0.75, respectively. Immunohistochemical Staining and Quantitative Reverse Transcription PCR revealed that the expression levels of tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6 were significantly lower in postburn keloids than in hypertrophic scars- ConclusionsTumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6, exhibiting high diagnostic accuracy, provide valuable guidance for the differential diagnosis and treatment of postburn pathological scars-

The Effects of Mesenchymal Stem Cells-Derived Exosomes on Metabolic Reprogramming in Scar Formation and Wound Healing.

Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.

Safety and efficacy of intralesional bleomycin for keloids and hypertrophic scars: A systematic review and meta-analysis.

Bleomycin, originally an antitumor drug, was explored as a pathological scar treatment in the mid-1990s. However, its efficacy and safety profile varies among individuals. This study aimed to assess topical bleomycin's efficacy and safety in treating hypertrophic scars and keloids. We reviewed randomized controlled trials (RCTs) and controlled clinical trials (CCTs) published in English, comparing intralesional bleomycin to placebos or common intralesional scar treatments. Primary outcomes included percentage change in scar improvement, pigmentation, recurrence, atrophy, pain, telangiectasia, ulceration, patient self-assessment, and observer assessment (>50%). Six trials met the criteria. Bleomycin significantly improved scar reduction compared to triamcinolone (p < 0.05). There was no significant difference in pigmentation (p = 0.05) and recurrence (p = 0.21) compared to other treatments. In terms of safety, bleomycin caused less skin atrophy (p < 0.01) and telangiectasia (p < 0.01) but more pain (p = 0.03) than other treatments. Bleomycin was more effective than TAC, 5-FU, or TAC combined with 5-FU for treating keloids and hypertrophic scars with lower skin atrophy and telangiectasia risks. However, it may cause more pain than 5-FU or TAC. Further comprehensive studies, including RCTs, are required for objective analysis.

The challenge of composite graft: the use of fluorescent light energy to improve engraftment

Composite graft is a useful tool for the reconstruction of specific facial aesthetic subunits with a single surgical stage. This technique, when successful, gives optimal results in the reconstruction of small defects of nose, ear, eyelid and lips. The aim of this work is to optimize the attachment of composite grafts in the reconstruction of small complex facial defects by combining it with Fluorescent Light Energy (FLE) during the healing process of the graft. The beneficial effects of photobiomodulation (PBM) on wound healing might be attributed to anti-inflammatory signaling, cell proliferation, protein synthesis, and decreased bacterial infection. We previously experienced rewarding achievements using Photonic energy in the treatment of burns, non-healing wounds and pathological scars. Therefore, we chose to exploit the potential of bioluminescent energy to maximize aesthetical and functional results, enhancing the formation of new vascular connections and modulating both inflammatory and scarring processes. From the 2nd postoperative day, the patients were locally treated with 5 FLE sessions every (48/72 h) 2 or 3 days. We evaluated results in terms of time for engraftment, quality of the scarring, infective complications and morbidity of the donor site. Graft survival is subject to many factors, both local and systemic. To overcome these issues, various methods have been studied and described. We here report the successful reconstruction of full-thickness defects of the free margin of the nasal alar rim and the central portion of the inferior lip with a composite graft. These results were highly encouraging if compared with the literature. By analyzing our small cohort, we demonstrated how new technologies may push this traditional reconstructive procedure beyond their old boundaries: overcoming an increased size demand or a potential infective wound environment.

Chemotherapy affects the development of pathological scarring after general thoracic surgery in children.

Globally, a great number of children have been suffering from physical dysfunction and psychological stress due to uncontrollable scar growth and a lack of effective modalities. Despite chemotherapy's established role as a primary treatment for pathological scarring in adults, its efficacy in preventing or minimizing scar formation in paediatric patients remains underexplored. This retrospective cohort study aimed to refine the relevant clinical evidence and investigate the effect of chemotherapy on pathological scars in children. In this single-centre retrospective cohort study, the data of children aged ≤18 years who underwent thoracic surgery at the Children's Hospital of Fudan University between 1 January 2018, and 31 December 2021 were assessed. The primary outcome was pathological scarring, and the secondary outcomes were subjective symptoms accompanying pathological scarring, such as pain and itching. To mitigate indication bias, analysis was performed by inverse probability weighting (IPTW) log-binomial regression models. The cohort comprised 102 children, among whom 36 received adjuvant chemotherapy perioperatively, while 66 did not. Under the IPTW model, a statistically significant difference in pathological scarring incidence was observed between the chemotherapy and non-chemotherapy groups (16.7% vs. 29.4%, p = 0.027). And the children received chemotherapy post-operatively had a lower relative risk of pathological scarring, compared with those received chemotherapy both before and after surgery (19.8% vs. 28.8%). Adjuvant chemotherapy treatment after surgery may reduce the incidence of post-operative pathological scarring in children.

Supercritical Fluids: An Innovative Strategy for Drug Development.

Nanotechnology plays a pivotal role in the biomedical field, especially in the synthesis and regulation of drug particle size. Reducing drug particles to the micron or nanometer scale can enhance bioavailability. Supercritical fluid technology, as a green drug development strategy, is expected to resolve the challenges of thermal degradation, uneven particle size, and organic solvent residue faced by traditional methods such as milling and crystallization. This paper provides an insight into the application of super-stable homogeneous intermix formulating technology (SHIFT) and super-table pure-nanomedicine formulation technology (SPFT) developed based on supercritical fluids for drug dispersion and micronization. These technologies significantly enhance the solubility and permeability of hydrophobic drugs by controlling the particle size and morphology, and the modified drugs show excellent therapeutic efficacy in the treatment of hepatocellular carcinoma, pathological scarring, and corneal neovascularization, and their performance and efficacy are highlighted when administered through multiple routes of administration. Overall, supercritical fluids have opened a green and efficient pathway for clinical drug development, which is expected to reduce side effects and enhance therapeutic efficacy.

A retrospective analysis of patients who underwent tracheal resection and end-to-end anastomosis surgery for benign tracheal stenosis, over a 10-year period

IntroductionLaryngotracheal stenosis encompasses a diverse range of diagnoses, encompassing complete or partial narrowing of various subgroups of the upper airways, including the laryngeal structures and trachea, due to pathological scar formation. This increasingly prevalent pathology is of significant importance due to its potential for life-threatening consequences. Among the defined treatment modalities, tracheal resection and end-to-side anastomosis remain a valuable therapeutic alternative in appropriate indications. ObjectiveThe objective of this study was to retrospectively evaluate the outcomes of patients who underwent tracheal resection and end-to-end anastomosis at our clinic over the past decade. Material & methodAll patients who underwent tracheal resection and end-to-end anastomosis surgery for benign tracheal stenosis at the Department of Otolaryngology, Mustafa Kemal University Hospital between 2013 and 2023 were included in the study. The diagnosis of tracheal stenosis was based on endoscopic examination and computed tomography results. Interventions without postoperative symptoms and without the need for additional surgical intervention were considered successful. The study was approved by Hatay Mustafa Kemal University Ethics Committee with decision number 2023/27. ResultsA total of 29 patients were included in the study. The mean age of the patients was 26.48 years. 3 patients (10.35 %) had a comorbidity. In all patients orotracheal intubation or intubation and tracheotomy was the aetiological cause. There were no intraoperative complications. In the postoperative period, wound infection was observed in 3 patients (10.35 %) and subcutaneous emphysema in 2 patients (6.9 %). In 1 patient (3.45 %) recurrent respiratory distress was observed, restenosis was considered and tracheotomy was performed. Our complication rate was 20.69 %. When all patients were evaluated at the end of the postoperative follow-up period, the surgical success rate was calculated to be 96.55 %. ConclusionWith a surgical success rate of 96.55 % and a low complication rate in our study, we believe, in parallel with previous studies, that open surgery is a reliable, physiologically appropriate and successful method among the current treatments for tracheal stenosis.

How to Keep Myofibroblasts under Control: Culture of Mouse Skin Fibroblasts on Soft Substrates

During the physiological healing of skin wounds, fibroblasts recruited from the uninjured adjacent dermis and deeper subcutaneous fascia layers are transiently activated into myofibroblasts to first secrete and then contract collagen-rich extracellular matrix into a mechanically resistant scar. Scar tissue restores skin integrity after damage but comes at the expense of poor esthetics and loss of tissue function. Stiff scar matrix also mechanically activates various precursor cells into myofibroblasts in a positive feedback loop. Persistent myofibroblast activation results in pathologic accumulation of fibrous collagen and hypertrophic scarring, called fibrosis. Consequently, the mechanisms of fibroblast-to-myofibroblast activation and persistence are studied to develop antifibrotic and prohealing treatments. Mechanistic understanding often starts in a plastic cell culture dish. This can be problematic because contact of fibroblasts with tissue culture plastic or glass surfaces invariably generates myofibroblast phenotypes in standard culture. We describe a straight-forward method to produce soft cell culture surfaces for fibroblast isolation and continued culture and highlight key advantages and limitations of the approach. Adding a layer of elastic silicone polymer tunable to the softness of normal skin and the stiffness of pathologic scars allows to control mechanical fibroblast activation while preserving the simplicity of conventional 2-dimensional cell culture.

Evidence of a causal relationship between blood pressure and pathological scars: a bidirectional Mendelian randomization study.

Recent advancements in basic medicine and epidemiology suggest a potential influence of blood pressure on scar formation, yet the specifics of this relationship are not fully understood. This study aims to clarify the causal link between blood pressure and the development of pathological scars using Mendelian randomization (MR). This study employed genetic variants closely linked to blood pressure as instrumental variables to explore the relationship between blood pressure and pathological scars. The inverse variance weighted (IVW) method was used for analysis. Our analysis identified a notable association where higher blood pressure was correlated with a lower risk of pathological scars. Specifically, an increase in diastolic blood pressure (odds ratio [OR] per standard deviation increase: 0.67 [95% Confidence Interval [CI], 0.49-0.99]), systolic blood pressure (OR per standard deviation increase: 0.66 [95% CI, 0.46-0.93]), and hypertension (pooled OR: 0.39 [95% CI, 0.18-0.85]) were significantly associated with a reduced risk of keloids. Similarly, a genetic predisposition to hypertension (pooled OR: 0.31 [95% CI, 0.11-0.89]) was significantly associated with a reduced risk of hypertrophic scars. Neither reverse MR analysis nor Steiger's test indicated a significant reverse causal relationship between hypertension and either keloids or hypertrophic scars. The findings suggest a protective role of higher blood pressure against the development of pathological scars, including keloids and hypertrophic scars. However, the inconsistency observed across different MR methods warrants cautious interpretation and underscores the need for further investigation to confirm these findings.

Mini review on collagens in normal skin and pathological scars: current understanding and future perspective.

Pathological scar tissues are characterized by the presence of overabundant collagens whose structure and organization are also different from those in unwounded skin. This causes scar tissues to lose some functions performed by normal skin, and currently, there are no effective measures to prevent scar formation. Inflammation has been shown to modulate fibroblast proliferation, differentiation, and function, hence collagen production and organization. In this minireview, we provide an overview of the current understanding of collagen, specifically collagen type I and III which are main collagens in skin, structure and fibre formation and highlight their differences between normal skin and pathological scars. We discuss the role that cytokines play in modulating fibroblast function. We also identify some potential research directions which could help to further our understanding of the complex and dynamic wound healing and scar formation process.