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Granulation tissue with inflammatory cells and congested blood vessels; hematoxylin–eosin color (objective 40x)
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Although the healing means 2 types of biological mechanisms that seem to be ‘pathologic’, the swell and the granulations are a normal process in the biology of the human being, representing two systemic functions: the adaptation and the morphogenesis.
There is a pathological healing in which the fundamental healing phenomenon is deviated from the n...
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Scars are generated in mature skin as a result of the normal repair process, but the replacement of normal tissue with scar tissue can lead to biomechanical and functional deficiencies in the skin as well as psychological and social issues for patients that negatively affect quality of life. Abnormal scars, such as hypertrophic scars and keloids, a...
Keloid is dermal lesion characterized by nodular fibroblastic proliferation, which is considered an aberration of wound healing process. It is believed to be the confused scar that does not know when to stop growing. Pressure therapy using clips or splints is widely used for the treatment of keloids; however, it is often very difficult to control t...
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 fro...
Although pressure therapy (PT) represents the standard care for prevention and treatment of hypertrophic scar (HS) from burns, its practice is largely based on empirical evidence and its effectiveness remains controversial. To clarify the effect of PT (15–25 mmHg) for HS, we performed the systematic review and meta-analysis. Several electronic data...
Citations
... triamcinolone, 5fluorouracil, bleomycin, etc.) has been recommended as the first-line treatment for keloids, and these standard treatments have not been revolutionized in the past decade [3,4]. Despite the gradual introduction of encouraging therapies, such as cryotherapy, into the routine treatment of keloids, longterm clinical outcomes remain poor due to the high posttreatment relapse rate [5,6]. A thorough understanding of the molecular mechanisms of keloid scarring may provide ideas and a research basis for improving existing treatment options and developing systemic or targeted therapies. ...
Keloids are a fibrotic disease caused by an excessive accumulation of extracellular matrix in the dermis; they have neoplasia-like properties of aggressive growth and high posttreatment recurrence rates. Therefore, it is imperative to gain additional insight into the pathobiology of keloid formation. Single-cell RNA sequencing (scRNA-seq) technology has brought data-driven innovation to understanding the pathogenesis of keloids by breaking the limitations of traditional sequencing technologies to resolve cell composition and to distinguish functional cell subtypes at an unprecedented resolution. The present review aims to cover the application of scRNA-seq technology in keloids and its exploratory findings, including the depiction of the cellular landscape of keloids, fibroblast heterogeneity, the lineage development of Schwann cells and the mesenchymal-activation phenomenon of endothelial cells. Furthermore, scRNA-seq records the transcriptional profiles of fibroblasts and immune cells in a more refined manner, and this gene expression information provides excellent material for inferring intercellular communication networks and lays an important theoretical foundation for future studies.
... Keloid, a kind of special scar, is formed through the abnormal and massive proliferation of fibroblasts from normal skin following trauma. Dermal-derived fibroblasts are the primary effector cells involved in keloid formation and are highly proliferative and resistant to apoptosis [10][11]. Moreover, fibroblasts are closely related to the development and clinical outcome of keloids [12][13]. ...
Background
The clinical features of keloids consist of aberrant proliferation, secretion, differentiation and apoptosis of keloid dermis-derived fibroblasts (KFBs). Notably, the apoptosis rate of KFBs is lower than the proliferation rate. Though the anti-fibrotic effect of adipose-derived stem cells (ADSCs) on keloids has become a hot topic of research, the exact anti-fibrotic mechanism of the paracrine effect remains unclear. This study aimed to find out how the conditioned medium of ADSCs (ADSC-CM) exerts an anti-fibrotic effect in KFBs.
Methods
KFBs and ADSCs were extracted and cultured. Then, ADSC-CM was prepared. Whether ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8, an 5-Ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. The expressions of cyclooxygenase-1 (COX-1), COX-2, caspase 3 and B-cell lymphoma-2 (Bcl-2) in ADSC-CM-cultured KFBs were tested by real-time PCR and western blotting. To clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis, a specific COX-2 inhibitor, celecoxib, was applied to KFBs cultured in ADSC-CM. Moreover, we tested the production of arachidonic acid (AA) and prostaglandin E2 (PGE2) by ELISA. Then, we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in vivo.
Results
The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly increased. Caspase 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured KFBs. Furthermore, ADSC-CM strikingly elevated COX-2 mRNA and protein expressions, but COX-1 expression was unaltered. COX-2 inhibitors reduced ADSC-CM-induced apoptosis. Additionally, COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 expression. ADSC-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 inhibition. In the nude mouse model, expressions of AA, COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injection than in the controls.
Conclusions
We showed activation of the COX-2/PGE2 cascade in KFBs in response to ADSC-CM. By employing a specific COX-2 inhibitor, COX-2/PGE2 cascade activation played a crucial role in mediating the ADSC-CM-induced KFB apoptosis and anti-proliferation effects.
... Other than that, symptoms of pruritis, pain, and restriction of movement were also reported to be more prevalent in keloids. 1,2 Various approaches are described in the literature for the management of keloidal scars, but there is no single proven method that guarantees of no-recurrence. Combination of treatment method has been advocated. ...
This article aims to share a simple method that can be adopted as part of treatment regimen of keloids. Two types of modified oyster splint was done and their usefulness is discussed. As an adjunct method, this device has shown to give a satisfactory result. Further investigation by clinical studies are invited.
... (8) All of the modern methods of preventing the formation of pathological scars after surgery cannot fundamentally affect the function of fibroblasts; therefore, many methods of prevention and treatment have been proposed. (9) One of the promising modern methods of accelerating the regeneration of fresh surgical wounds and the prevention of pathological scarring is the introduction into the wound area of various cultures of embryonic fibroblasts (10) and mesenchymal stem cells (MSCs). (11) In the case of embryonic fibroblasts, they enhance wound healing without scarring in the prenatal period in mammals and humans; (12) in the case of MSCs, they introduce the possibility of differentiating into different cells of the regenerative cascade. ...
The purpose of this study was to optimize healing and prevent the formation of unaesthetic scars of the maxillofacial region by transplanting xenogenic dermal fibroblasts (XDFs) into a fresh surgical wound.
Materials and Methods: A total of 26 patients were selected with formations located on the skin of the face and neck, which could be compared with symmetrical areas of the healthy side. The patients were divided into 2 groups—the main group (Group 1) and the control group (Group 2). In Group 2 (n=12), a neoplasm was dissected, followed by grafting with local tissues, and in the Group 1 (n=14), a culture suspension of XDFs was injected by a tunnel method into the wound edges before stitching. The area of scar formation was determined using the LesionMeter program for the Android operating system. Contact thermography was carried out using thermo indicator films (CelluVision kit, IPS Italy).
Results: The analysis of the parameters of the young scar formation on Day 30 after the operation makes it possible to state that the introduction of cell culture of XDFs in the wound edges has a positive effect on the healing rate of surgical wounds, decreases the inflammatory response and contributes to the development of a distinctively positive scar in terms of its quality and functional characteristics. By Day 30, the primary surgical wound area was reduced by 67.69%, and 71.43% of patients had soft and thin aesthetic scars with microcirculation that were not distinguishable from the surrounding skin and the skin of symmetrical areas of the face or neck. In patients of the control group, without fibroblast transplantation, the area decreased by only 50.0% and aesthetic scars were formed only in 41.67% of cases. In 16.67% of patients, the presence of wide, dense, cold (due to weak vascularization) hypotrophic scars was noted. Hyperthermia persists around these scars, indicating a weak inflammatory response.
Conclusion: The use of a cell culture suspension of XDFs in the treatment of postoperative surgical wounds opens up new real possibilities for reducing the incidence of inflammatory reactions, stimulates healing processes and contributes to the development of more functionally and aesthetically acceptable scars on the face and neck.
... T he multi-micro stromal stimulation system therapy is an electromedical device with the basic claim is to reactivate the mesenchymal tissue either in surfaceal or deep subcutis but also pre-and postfascial layers by stimulating the elastic fibers and sucking-squeezing the fat cells and the microareolar spaces. [1][2] The aim is to en-hance the interstitial tissue compliance to such a biphasic mechanical activation, energetically spreading oxygen and micronutrients through the cell membrane barrier to subcellular organs (e.g. mitochondria and ribosomes) uptake and metabolism. ...
BACKGROUND: The multi-micro stromal stimulation system electromedical device is effective upon interstitial sub-dermal and subcutaneous spaces re-balancing elastic fibers, fat cells and microareolar spaces of mesenchyme to promote body remodeling. Our spontaneous and anecdotal study investigates the benefits of microalveolar stimulation treatment in feet, ankles and legs remodeling in patients affected by mild lymphedema of calves and legs.
METHODS: Twenty-five female patients were recruited in this study. icoone ® robotized device was used for its peculiar skin suction pressing and rotating function. The circumferences of foot, ankle and leg were measured before starting the treatment, after 1 month of treatment, and 1 month after the interruption. in addition, skin parameters (elasticity and dermis embedding) were analyzed before and at the end of the treatment. Finally, a self-reported questionnaire was administered in order to assess the benefits of icoone ® treatment.
RESULTS: A significant reduction of foot, ankle and leg circumference was observed after 1 month (P=0.019; P=0.001; P=0.002 respectively). A significant correlation was present between the BMI and leg circumference measured before starting the treatment (P=0.002). A significant increase of skin elasticity (P=0.01) and reduction of skin dermis embedding (P=0.001) were registered after 1 month. Patients reported subjective legs lightness feelings, enhanced micturition, sparkling energy and wellbeing after each session. A more appealing esthetic outcome was also self-judged at the end of the treatment.
CONCLUSIONS: icoone ® suction therapy provides objective and subjective evidences of cosmetic and microcirculation functional improvement, especially in patients younger than 40 years old.
... Quando a derme e a fáscia são afetadas por cicatrizes, essas estruturas são alteradas, sua função e capacidade de interação com o ambiente externo e interno tornam-se diminuídas. A proporção de tais eventos em cada indivíduo depende da vários fatores, como a predisposição genética e idade, mas ainda não são claramente compreendidos [3,4]. Atualmente, o panorama científico oferece algumas possibilidades de explicação, mas as de maior aceitação são as hipóteses de inflamação neuroinflamatória ou a neurogênica. ...
A cesariana é a intervenção cirúrgica mais prevalente em mulheres. Estudos descrevem perturbações musculoesqueléticas quando um tecido é comprometido como, por exemplo, a perda da continuidade ocasionada pela cicatriz. O objetivo do estudo foi analisar os efeitos da bandagem elástica na redução da queixa de dor local em estático, dor ao movimento, sensibilidade dolorosa, flexibilidade e função vascular em pacientes com sintomas musculoesqueléticos, submetidas à cirurgia de cesariana. Foram avaliadas trinta mulheres, pacientes do ambulatório de Fisioterapia ortopédica, com no mínimo dezoito anos de idade. Foram avaliadas antes e depois de 24 horas da aplicação da técnica, a dor, com algometria e escala numérica, a flexibilidade, com fita métrica e alterações vasculares, pela termografia. A aplicação da bandagem ocorreu em sentido transversal ou longitudinal da cicatriz com tensão de 50%. Para análise estatística foram utilizados os testes T-Student e Wilcoxon, para variáveis paramétricas e não paramétricas respectivamente, o nível de significância foi de 5%. Os resultados demonstraram uma diminuição das queixas de dor em geral (p = 0,004), dor ao movimento (p = 0,02), sensibilidade dolorosa (p = 0,0001), flexibilidade (p = 0,047) e condição vascular (p = 0,027). Foi possível observar, que após a aplicação da bandagem elástica todas as variáveis analisadas tiveram melhora significativa em relação à condição inicial.Palavras-chave: cesárea, bandagem elástica, cicatriz, cirurgia, dor.
... At present, the clinical treatment of keloids is not ideal and is easy to relapse after resection. 2 Microenvironmental hypoxia is a common feature of many diseases and can cause the production of a series of adaptive responses to maintain oxygen homeostasis. 3 A large number of transcription factors are involved in hypoxia response, while hypoxia-inducible factor (HIF)-1 is considered to be an important transcription factor mediating hypoxia response. ...
The aim of this study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in keloids and its correlation with inflammatory responses and apoptosis. The keloid specimens resected in our hospital from November 2015 to February 2017 were selected as the pathological group, and the normal skin tissues from our hospital during the same period were selected as the control group. The expression of HIF-1α, inflammatory response cytokines, and apoptotic molecules in the tissues of two groups were detected. The messenger RNA (mRNA) expression of HIF-1α in the keloids in the pathological group was significantly higher than that in the control group, and the mRNA expression of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the pathological group was significantly higher than those in the control group. The mRNA expression of Bax in the pathological group was significantly higher than that in the control group. The mRNA expression of Bcl-2, livin, and hPEBP4 in the pathological group was significantly lower than that in the control group. Pearson test showed that there was a positive correlation between the mRNA expression of HIF-1α and inflammatory cytokines including IL-1β, IL-2, IL-6, and TNF-α. There were also a positive correlation between the mRNA expression of HIF-1α and Bax and a negative correlation between the mRNA expression of HIF-1α and Bcl-2, livin, and hPEBP4. In conclusion, HIF-1α was highly expressed in keloids and closely related to inflammatory response cytokines and apoptosis molecules. Increased expression of HIF-1α in keloids may be an important factor in inflammatory responses and increased apoptosis in skin tissues.
... The incidence of hypertrophic scars and keloids varies with age, race, sex, anatomic location, and the inciting trauma. Associated symptoms such as pruritus, dysesthesia, and pain, as well as restricted range of motion and contracture formation may be observed with both keloids and hypertrophic scars but tend to be more prevalent with keloids [1,2]. ...
The aim of this review was to explore the existing body of literature focusing on the intralesional treatments of keloids and hypertrophic scars.
A comprehensive systematic review of related articles was conducted across multiple databases. Article selection was limited to those published in the English language between 1950 and 2014. Search terms for the on-line research were “scar(s),” “keloid(s),” “hypertrophic,” “injection,” “intralesional,” and “treatment”.
The initial search returned 2548 published articles. After full text review, the final search yielded 11 articles that met inclusion criteria. A total of 14 patient samples in 11 articles were collected. The most frequent intralesional injection treatment studied was triamcinolone (n = 5), followed by bleomycin (n = 3), 5-fluorouracil (n = 2), verapamil (n = 2), cryosurgery, and collagenase. The scar height reduction for all but one study was demonstrated, with acceptable complication and recurrence rate. Only three articles reported a follow-up period longer than 18 months, and only two studies used standardized outcome criteria with a quantitative scale.
Although many treatment options have already been described in the literature, there is no universally accepted treatment resulting in permanent hypertrophic or keloid scar ablation. The lack of adequately long-term powered randomized controlled trials does not permit to establish definitive conclusions with implications for routine clinical practice.
Level of evidence
... 25 A KS not only increases in height but also proliferates beyond the borders of the original lesion. 29 KSs and HSs may represent two different stages of the same disease. 30,31 The AS appears as a cutaneous depression. ...
... Many are the reasons that provoke such events, from genetic predisposition, to age, but they are still not clearly understood. 29,33 At this time, the scientific panorama offers several hypotheses, but the most endorsed is mainly the neuroinflammatory or neurogenic inflammation hypothesis. ...
Every element or cell in the human body produces substances that communicate and respond in an autocrine or paracrine mode, consequently affecting organs and structures that are seemingly far from each other. The same also applies to the skin. In fact, when the integrity of the skin has been altered, or when its healing process is disturbed, it becomes a source of symptoms that are not merely cutaneous. The skin is an organ, and similar to any other structure, it has different functions in addition to connections with the central and peripheral nervous system. This article examines pathological responses produced by scars, analyzing definitions and differences. At the same time, it considers the subcutaneous fascias, as this connective structure is altered when there is a discontinuous cutaneous surface. The consequence is an ample symptomatology, which is not limited to the body area where the scar is located, such as a postural or trigeminal disorder.
... Keloids and EGT contain synthetic fibroblasts that overproduce extracellular matrix (ECM) and favor collagen deposition, instead of differentiating into quiescent fibrocytes or undergoing cell death via apoptosis. [17][18][19] Cultured fibroblasts isolated from keloids have distinct population characteristics. 20 Research suggests that EGT fibroblasts are also a distinct population based on proliferation, collagen synthesis and cytokine secretion. ...
To compare histopathologic features of a fibroproliferative disorder in horses (exuberant granulation tissue-EGT) and people (keloid).
Archival tissue samples of EGT (n = 8) and keloid (12).
After automated hematoxylin and eosin, histochemical (Gomori trichrome, Verhoeff-van Gieson elastin) and immunohistochemical (vimentin, α-smooth muscle actin, CD34, CD68, CD117) stainings, tissue sections were evaluated using a semi-quantitative grading scale for presence or absence of ulceration, keloidal collagen, myofibroblasts, and elastic fibers as well as degree of inflammation, fibrosis, vascularity, and orientation of collagen fibers.
Superficial dermis and deep dermis of both horses and people had increased numbers of haphazardly oriented thickened collagen fibers; however, only keloids contained "keloidal" collagen. Fibroblast numbers were markedly increased in both groups but only EGT had myofibroblasts. Minimal vascularity was observed in the deep dermis of both groups. The superficial dermis in EGT was characterized by small vessels within immature granulation tissue. Macrophages and mast cells were infrequently found in both groups but polymorphonuclear cells were markedly increased in EGT.
Humans and horses are the only mammals known to naturally develop excessive granulation during wound healing; however, similarities and differences between fibroblast populations and associated collagen have not been reported. Inflammatory response may contribute to observed differences in the cellular populations, with EGT possessing markedly increased myofibroblasts, small vessels, and acute inflammatory cells compared with keloids. Further work is warranted to develop common treatment strategies for these fibroproliferative conditions.
