scholarly journals Hypertrophic Scars and Keloids – Contemporary Concepts and Treatment Options

2014 ◽  
Vol 41 (1) ◽  
pp. 57-74 ◽  
Author(s):  
Y. P. Yordanov ◽  
A. Shef
Keyword(s):  
Wound Healing ◽  
Normal Skin ◽  
Treatment Options ◽  
Cell Activity ◽  
Scar Tissue ◽  
Medical Problem ◽  
Scar Formation ◽  
Hypertrophic Scars ◽  
Inflammatory Processes ◽  
Reparative Process

Summary Wound reparative process after surgery, burns, injuries, and inflammatory processes results in a spectrum of scar formation ranging from nearly scarless healing to excessive fibrosis or atrophy. Scarring is considered a major medical problem that leads to aesthetic and functional sequelae. Scar tissue is clinically distinguished from normal skin by an aberrant color, rough surface texture, increased thickness (hypertrophy), occurrence of contraction, and firmness. In the last decade, the concept of wound healing kinetics has been developed to describe the delicate balance of cell activity involved in scar formation and remodeling. Hypertrophic scars and keloids are formed as a result of the process of abnormal wound healing. Despite all that has been written on improving the appearance of these types of scars, there are no definitive management protocols. The aim of the present article is to make a brief review of the basic wound healing, while focusing on medicine’s latest understanding of the development and treatment of keloids and hypertrophic scars.

Polymeric Nanofibre Scaffold for the Delivery of a Transforming Growth Factor β1 Inhibitor

2017 ◽  
Vol 70 (3) ◽  
pp. 280 ◽  
Author(s):  
Vipul Agarwal ◽  
Fiona M. Wood ◽  
Mark Fear ◽  
K. Swaminathan Iyer
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Normal Skin ◽  
Scar Tissue ◽  
Transforming Growth Factor Β1 ◽  
Collagen I ◽  
Elevated Concentration ◽  
Skin Wound Healing

Skin scarring is a highly prevalent and inevitable outcome of adult mammalian wound healing. Scar tissue is both pathologically and aesthetically inferior to the normal skin owing to elevated concentration of highly orientated collagen I architecture in the innate repaired tissue. With highly invasive surgery being the main treatment modality, there is a great need for alternative strategies to mitigate the problem of scar formation. Tissue engineering approaches using polymeric scaffolds have shown tremendous promise in various disease models including skin wound healing; however, the problem of skin scarring has been greatly overlooked. Herein, we developed an electrospun poly(glycidyl methacrylate) (ES-PGMA) scaffold incorporating a small-molecule antiscarring agent, PXS64. PXS64, a lipophilic neutral analogue of mannose-6-phosphate, has been shown to inhibit the activation of transforming growth factor β1 (TGFβ1). TGFβ1 is a primary protein cytokine regulating the expression of collagen I during wound healing and therefore governs the formation of scar tissue. The nanofibres were tested for biocompatibility as a tissue engineering scaffold and for their efficacy to inhibit TGFβ1 activation in human dermal skin fibroblasts.

scholarly journals Local and Remote Effects of Mesenchymal Stem Cell Administration on Skin Wound Regeneration

2021 ◽  
Vol 28 (3) ◽  
pp. 355-373
Author(s):  
Ekaterina Silina ◽  
Victor Stupin ◽  
Konstantin Koreyba ◽  
Sergey Bolevich ◽  
Yulia Suzdaltseva ◽  
...  
Keyword(s):  
Wound Healing ◽  
Direct Injection ◽  
Medical Problem ◽  
Local Effect ◽  
Skin Wound ◽  
Regeneration Process ◽  
Control Group ◽  
Skin Wound Healing ◽  
Inflammatory Processes ◽  
Series Of Experiments

Wound healing is an important medical problem. We evaluated the efficacy of locally administered mesenchymal stem cells (MSCs) isolated from human umbilical cords on the dynamics of skin wound healing. The study was conducted on the backs of Wistar rats, where two square wounds were created by removing all layers of the skin. Four groups were studied in two series of experiments: (1) a Control_NaCl group (the wounds were injected with 0.9% NaCl solution) and a Control_0 group (intact wounds on the opposite side of the same rat’s back); (2) an MSC group (injected MSCs, local effect) and a Control_sc group (intact wounds on the opposite side of the back, remote MSC effect). The area and temperature of the wounds and the microcirculation of the wound edges were measured. Histological and morphometric studies were performed on days 3 and 7 after the wounds were created. The results showed that the injection trauma (Control_NaCl) slowed the regeneration process. In both MSC groups (unlike in either control group), we observed no increase in the area of the wounds; in addition, we observed inhibition of the inflammatory process and improved wound regeneration on days 1–3 in the remote group and days 1–5 in the local (injected) group. The MSC and Control_sc groups demonstrated improved microcirculation and suppression of leukocyte infiltration on day 3. On day 7, all the studied parameters of the wounds of the Control_0 group were the same as those of the wounds that received cell therapy, although in contrast to the results of the Control_ NaCl group, fibroblast proliferation was greater in the MSC and Control_sc groups. The dynamics of the size of the wounds were comparable for both local and remote application of MSCs. Thus, even a one-time application of MSCs was effective during the first 3–5 days after injury due to anti-inflammatory processes, which improved the regeneration process. Remote application of MSC, as opposed to direct injection, is advisable, especially in the case of multiple wounds, since the results were indistinguishable between the groups and injection trauma was shown to slow healing.

Nonsurgical Treatment of Keloids and Hypertrophic Scars

2019 ◽  
Vol 35 (03) ◽  
pp. 260-266
Author(s):  
Robert Saddawi-Konefka ◽  
Deborah Watson
Keyword(s):  
Scar Tissue ◽  
Scar Formation ◽  
Model Systems ◽  
Hypertrophic Scars ◽  
Limited Data ◽  
Controlled Clinical Trials ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Scar Quality ◽  
Accepted Form

AbstractDespite the ubiquitous nature of scar tissue, there is not a single, reliable strategy to prevent or treat excessive scarring. The difficulty in arriving at a universally accepted form of management is multifaceted: there is an incomplete understanding of the complex pathophysiology of scar formation; a lack of common metrics hampers the accurate description of scar quality and characteristics; model systems do not exist for proper investigation in the controlled environment of a laboratory; and there is only limited data from prospective, randomized controlled clinical trials. Accordingly, the management of cutaneous scars is typically based upon the experience from practitioners rather than from evidence-based data. This article will review the pathophysiology of excessive scar formation, define the most common scars—hypertrophic scars and keloids—and discuss the evidence to support the current nonsurgical therapies in use to both prevent and treat excessive scars.

scholarly journals Single cell landscape of hypertrophic scars identifies serine proteases as key regulators of myofibroblast differentiation

2020 ◽  
Author(s):  
Vera Vorstandlechner ◽  
Maria Laggner ◽  
Dragan Copic ◽  
Yiyan Chen ◽  
Bahar Golabi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Serine Proteases ◽  
Hypertrophic Scar ◽  
Normal Skin ◽  
Cell Types ◽  
Scar Formation ◽  
Myofibroblast Differentiation ◽  
Hypertrophic Scars ◽  
Dipeptidyl Peptidase 4

AbstractDespite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study we performed single-cell sequencing of mature human hypertrophic scars and developing scars in mice.Compared to normal skin, we found significant differences in gene expression in most cell types present in scar tissue. Fibroblasts (FBs) showed the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine FBs during scar development with genes highly expressed in mature human hypertrophic scars, we identified a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), were further analyzed in functional assays, revealing a role in TGFβ1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix (ECM) without interfering with the canonical TGFβ1-signaling pathway.In this study, we delineate the genetic landscape of hypertrophic scars and present new insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis.

scholarly journals The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Yang Li ◽  
Min Li ◽  
Caijie Qu ◽  
Yongxi Li ◽  
Zhanli Tang ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Immune Cell ◽  
Normal Skin ◽  
Cell Activity ◽  
Scar Tissue ◽  
Gene Expression Omnibus ◽  
Genomic Expression ◽  
Keloid Formation

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.

scholarly journals Single cell sequencing identifies serine proteases as regulators of myofibroblast differentiation

2020 ◽  
Author(s):  
Vera Vorstandlechner ◽  
Maria Laggner ◽  
Dragan Copic ◽  
Yiyan Chen ◽  
Bahar Golabi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Serine Proteases ◽  
Hypertrophic Scar ◽  
Normal Skin ◽  
Scar Formation ◽  
Myofibroblast Differentiation ◽  
Hypertrophic Scars ◽  
Dipeptidyl Peptidase 4 ◽  
Single Cell Sequencing

Abstract Despite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study we performed single-cell sequencing of mature human hypertrophic scars and developing scars in mice. Compared to normal skin, we found significant differences in gene expression in most cell types present in scar tissue. Fibroblasts (FBs) showed the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine FBs during scar development with genes highly expressed in mature human hypertrophic scars, we identified a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), were further analyzed in functional assays, revealing a role in TGFβ1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix (ECM) without interfering with the canonical TGFbeta1-signaling pathway. In this study, we delineate the genetic landscape of hypertrophic scars and present new insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis.

scholarly journals The Roles of Inflammation in Keloid and Hypertrophic Scars

2020 ◽  
Vol 11 ◽  
Author(s):  
Zheng-Cai Wang ◽  
Wan-Yi Zhao ◽  
Yangyang Cao ◽  
Yan-Qi Liu ◽  
Qihang Sun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Immune Cells ◽  
Scar Formation ◽  
Signal Transduction Pathways ◽  
Hypertrophic Scars ◽  
Local Inflammation ◽  
Traditional Role ◽  
Determining Factors ◽  
Intracellular Signal ◽  
Underlying Mechanisms

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.

scholarly journals The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vera Vorstandlechner ◽  
Maria Laggner ◽  
Dragan Copic ◽  
Katharina Klas ◽  
Martin Direder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Serine Proteases ◽  
Hypertrophic Scar ◽  
Normal Skin ◽  
Dipeptidyl Peptidase ◽  
Scar Formation ◽  
Hypertrophic Scars ◽  
Dipeptidyl Peptidase 4

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

Fibroblasts During Hypertrophic Scar Formation and Resolution

1973 ◽  
Vol 31 ◽  
pp. 428-429
Author(s):  
C. W. Kischer
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Cell Proliferation ◽  
Fine Structure ◽  
Metabolic Activity ◽  
Hypertrophic Scar ◽  
Normal Skin ◽  
Ground Substance ◽  
Hypertrophic Scars ◽  
Scanning Electron

The morphology of the fibroblasts changes markedly as the healing period from burn wounds progresses, through development of the hypertrophic scar, to resolution of the scar by a self-limiting process of maturation or therapeutic resolution. In addition, hypertrophic scars contain an increased cell proliferation largely made up of fibroblasts. This tremendous population of fibroblasts seems congruous with the abundance of collagen and ground substance. The fine structure of these cells should reflect some aspects of the metabolic activity necessary for production of the scar, and might presage the stage of maturation.A comparison of the fine structure of the fibroblasts from normal skin, different scar types, and granulation tissue has been made by transmission (TEM) and scanning electron microscopy (SEM).

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