Formation of hypertrophic scars: Evolution and susceptibility

Delavary, Babak Mahdavian; Veer, Willem M. van der; Ferreira, José Alexandre; Niessen, Frank B.

doi:10.3109/2000656x.2012.669184

Cited by 65 publications

(32 citation statements)

References 23 publications

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“…The phenotypic differences were stable over time in culture, suggesting that they are an inherent property of the cells. Furthermore, the key differences did not depend on whether skin cells originated from breast or abdominal skin, both prone to scar formation [23], [24], suggesting that the differences to GFBLs are a general characteristic of SFBLs. Whether this phenotypic difference depends on embryonic origin of the cells remains to be shown, as gingival cells mostly originate from the neural crest while abdominal and breast SFBLs are of mesodermal origin [11], [17].…”

Section: Discussionmentioning

confidence: 93%

“…For instance, they retain stem or tumor stromal cell phenotype better than traditional 2D cultures [21], [22]. Therefore, in the present study, the 3D culture model was used to compare the phenotype of human oral mucosal fibroblasts from attached gingiva, tissue characterized by little scar formation, with fibroblasts from human breast and abdominal skin, two areas of skin prone to excessive scar formation [23], [24]. The findings showed that gingival fibroblasts proliferated faster and expressed significantly higher levels of molecules that are involved in modulation of inflammation and ECM remodeling (MMPs), while skin cells showed significantly elevated expression of TGF-β signaling, ECM, myofibroblast and cell contractility-related genes.…”

Section: Introductionmentioning

confidence: 99%

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Human Gingival Fibroblasts Display a Non-Fibrotic Phenotype Distinct from Skin Fibroblasts in Three-Dimensional Cultures

et al. 2014

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Scar formation following skin injury can be a major psychosocial and physiological problem. However, the mechanisms of scar formation are still not completely understood. Previous studies have shown that wound healing in oral mucosa is faster, associates with a reduced inflammatory response and results to significantly reduced scar formation compared with skin wounds. In the present study, we hypothesized that oral mucosal fibroblasts from human gingiva are inherently distinct from fibroblasts from breast and abdominal skin, two areas prone to excessive scar formation, which may contribute to the preferential wound healing outcome in gingiva. To this end, we compared the phenotype of human gingival and skin fibroblasts cultured in in vivo-like three-dimensional (3D) cultures that mimic the cells' natural extracellular matrix (ECM) niche. To establish 3D cultures, five parallel fibroblast lines from human gingiva (GFBLs) and breast skin (SFBLs) were seeded in high density, and cultured for up to 21 days in serum and ascorbic acid containing medium to induce expression of wound-healing transcriptome and ECM deposition. Cell proliferation, morphology, phenotype and expression of wound healing and scar related genes were analyzed by real-time RT-PCR, Western blotting and immunocytochemical methods. The expression of a set of genes was also studied in three parallel lines of human abdominal SFBLs. Findings showed that GFBLs displayed morphologically distinct organization of the 3D cultures and proliferated faster than SFBLs. GFBLs expressed elevated levels of molecules involved in regulation of inflammation and ECM remodeling (MMPs) while SFBLs showed significantly higher expression of TGF-β signaling, ECM and myofibroblast and cell contractility-related genes. Thus, GFBLs display an inherent phenotype conducive for fast resolution of inflammation and ECM remodeling, characteristic for scar-free wound healing, while SFBLs have a profibrotic, scar-prone phenotype.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Human Gingival Fibroblasts Display a Non-Fibrotic Phenotype Distinct from Skin Fibroblasts in Three-Dimensional Cultures

et al. 2014

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“…Several published studies consist of retrospective case note reviews where any documentation of a scar which is red or raised constitutes a diagnosis of HTS [5, 9]. Other studies use the height of the scar alone [10, 11] or VSS [12] to diagnose HTS. In addition, some papers consider hypertrophic scars alone whereas others combine HTS with contracted or keloid scars to give an overview of pathological scarring [13].…”

Section: Discussionmentioning

confidence: 99%

A prospective study of time to healing and hypertrophic scarring in paediatric burns: every day counts

et al. 2017

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BackgroundIt is commonly accepted that burns taking longer than 3 weeks to heal have a much higher rate of hypertrophic scarring than those which heal more quickly. However, some of our patients develop hypertrophic scars despite healing within this 3-week period.MethodsWe performed a prospective study of 383 paediatric burns treated non-operatively at a regional burns centre over a 2-year period from May 2011 to April 2013. Scar assessment was performed by a senior burns therapist using the Vancouver Scar Scale.ResultsOverall rates of hypertrophic scarring were 17.2%. Time to healing was the strongest predictor of developing hypertrophic scarring, and the earliest hypertrophic scar developed in a patient who was healed after 8 days. The risk of hypertrophic scarring was multiplied by 1.138 for every additional day taken for the burn wound to heal. There was a trend towards higher rates of hypertrophic scarring in non-white skin types but this did not reach statistical significance.ConclusionsThe risk of hypertrophic scarring increases with every day and, therefore, every effort should be made to get the wound healed as quickly as possible, even within the traditional 3-week period usually allowed for healing. We believe that the traditional dogma of aiming for healing within 3 weeks is overly simplistic and should be abandoned: in paediatric burns, every day counts.Trial registrationNot applicable.

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“…There is difficulty comparing results between existing studies due to different denominators and sample sizes, heterogeneous patient populations, a lack of consistent definitions of risk factors and a lack of consistent and valid scar outcome classification [8]. Despite the high prevalence of hypertrophic scarring as a complication of burn injury, few prospective studies have been conducted to systematically identify factors associated with their occurrence in children [9], and hypertrophic scars and keloids are not always well-differentiated [10]. …”

Section: Introductionmentioning

confidence: 99%

Identification of factors predicting scar outcome after burn injury in children: a prospective case-control study

et al. 2017

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BackgroundThere is a lack of rigorous research investigating the factors that influence scar outcome in children. Improved clinical decision-making to reduce the health burden due to post-burn scarring in children will be guided by evidence on risk factors and risk stratification. This study aimed to examine the association between selected patient, injury and clinical factors and the development of raised scar after burn injury. Novel patient factors were investigated including selected immunological co-morbidities (asthma, eczema and diabetes type 1 and type 2) and skin pigmentation (Fitzpatrick skin type).MethodsA prospective case-control study was conducted among 186 children who sustained a burn injury in Western Australia. Logistic regression was used to explore the relationship between explanatory variables and a defined outcome measure: scar height measured by a modified Vancouver Scar Scale (mVSS).ResultsThe overall correct prediction rate of the model was 80.6%; 80.9% for children with raised scars (>1 mm) and 80.4% for children without raised scars (≤1 mm). After adjustment for other variables, each 1% increase in % total body surface area (%TBSA) of burn increased the odds of raised scar by 15.8% (95% CI = 4.4–28.5%). Raised scar was also predicted by time to healing of longer than 14 days (OR = 11.621; 95% CI = 3.727–36.234) and multiple surgical procedures (OR = 11.521; 1.994–66.566).ConclusionsGreater burn surface area, time to healing of longer than 14 days, and multiple operations are independently associated with raised scar in children after burn injury. Scar prevention strategies should be targeted to children with these risk factors.

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Formation of hypertrophic scars: Evolution and susceptibility

Cited by 65 publications

References 23 publications

Human Gingival Fibroblasts Display a Non-Fibrotic Phenotype Distinct from Skin Fibroblasts in Three-Dimensional Cultures

Human Gingival Fibroblasts Display a Non-Fibrotic Phenotype Distinct from Skin Fibroblasts in Three-Dimensional Cultures

A prospective study of time to healing and hypertrophic scarring in paediatric burns: every day counts

Identification of factors predicting scar outcome after burn injury in children: a prospective case-control study

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