Scar Formation: The Spectral Nature of Fetal and Adult Wound Repair

Ferguson, Mark W. J.; Whitby, David; Shah, Mamta; Armstrong, James J.; Siebert, John W.; Longaker, Michael T.

doi:10.1097/00006534-199604000-00029

Cited by 154 publications

(104 citation statements)

References 36 publications

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“…It is well established that skin wounds in the early gestation fetus heal without scar formation and fibrosis in contrast with similar wounds in adults (6,9,13,20,21,30). The histological phenotype of such wounds is shown to be composed of a loose array of uncontracted connective tissue collagen fibers, which may suggest fetal dermal fibroblasts have a reduced ability to contract the collagen matrix.…”

Section: Discussionmentioning

confidence: 99%

“…WOUND HEALING IN THE FETUS up to early third trimester of gestation is completely regenerative, proceeding in a scarless and nonfibrotic manner in contrast with wounds in adults (6,9,13,20,21,30). The reason for this difference is poorly understood, but there is evidence that the nature of fetal wound tissue and attributes of the cells, specifically fetal fibroblasts capacity for collagen contraction, is important.…”

mentioning

confidence: 99%

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Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts

Navarro¹,

Rezaiekhaligh²,

Keightley³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Acute lung injury involving extremely immature lungs often heals without excessive fibrosis unlike later in gestation and in adults. Several factors may be involved, but fibroblast contraction of collagen has been linked to the level of wound fibrosis. To assess whether human lung fibroblasts of fetal versus adult origin differ in ability to contract collagen and define the molecular underpinnings, we performed three-dimensional collagen contraction assay, analyzed their differential mRNA profile, specifically for transforming growth factor-β (TGF-β) signaling pathway and extracellular matrix components, studied the cell response to TGF-β in culture, and used two-dimensional gel electrophoresis followed by mass spectrometry to identify differences in their overall proteomes. Human lung fetal fibroblasts contracted the collagen matrix less than the adults. Smooth muscle actin expression did not differ. TGF-β stimulation resulted in greater Smad3 phosphorylation in fetal compared with adults. mRNA and proteomic profiling reveal a number of TGF-β pathways, ECM components, and cytoskeletal regulatory molecules are differentially expressed between the cell types. Of note is TGF-β receptor interacting protein 1 (TRIP-1), which we show inhibits fibroblast collagen contraction and is higher in fetal than adult fibroblasts. We conclude that human lung fetal fibroblasts are less able to contract collagen than adult lung fibroblasts. The diminished ability is not due to impediment of Smad3 activation but rather, at least in part, due to their higher level of TRIP-1 expression. TRIP-1 is a novel modulator of fibroblast collagen contraction.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts

Navarro¹,

Rezaiekhaligh²,

Keightley³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…For instance, various strategies to reduce the activity of transforming growth factor ft 2 at the wound site have all proved to have anti-scarring effects (Whitby and Ferguson, 1991a,b;Armstrong and Ferguson, 1995). The possibility of the therapeutic reduction of human scarring after surgery is extremely promising (Ferguson et al, 1996). This will also reduce the number of secondary operations due to "scar-related" complications.…”

Section: Gene Therapymentioning

confidence: 99%

Treatment Outcome in Cleft Lip and Palate: Issues and Perspectives

Mølsted¹

1999

Critical Reviews in Oral Biology & Medicine

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In the last 40 years, great progress has been made toward a better understanding of many aspects of the cleft lip and palate defect, but there is still a long way to go before there is agreement on the optimal treatment procedures. With regard to the primary operations, it can be stated, in a somewhat simplified form, that there are two main schools of thought in cleft treatment. One advocates early closure of the lip and palate, a procedure which imparts a high priority to early speech function. The other recommends delayed closure of the hard palate, thereby according a high priority to the growth of the maxilla A number of intercenter and multicenter studies have been carried out recently in an effort to elucidate which procedures give the best result, both esthetically and functionally. The results are ambiguous, and this has led a number of researchers to suggest that the randomized clinical trial is the only way to resolve the ambiguity, The fact that it has proved difficult to identify the optimal procedures in the field of cleft lip and palate treatment need not only be due to a less than optimal research design, a contributory factor might also be the great variability in craniofacial morphology and in the response to treatment in patients who have exactly the same cleft lip and palate diagnosis. Intensive research has made it possible to state categorically that clefts occur due to many different factors in an interplay between genetics and environment. Therefore, it is not likely that a single gene can be responsible for clefting. Since scar tissue presents many problems-for instance, impairment of growth-the reduction or prevention of scar formation has long been a desirable goal. The discovery that a fetus can heal without scar formation has led to many animal experiments. The timing of the surgical intervention on fetuses is critical, since lategestation fetuses heal with adult-like scarring. There are still many unsolved problems connected with fetal surgery, and at present prenatal surgery for repair of cleft lip and palate is not ethically defensible in humans. On the other hand, it appears that there are considerable possibilities for the reduction of human scarring after surgery with the introduction of various woundhealing medications.

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“…1 A dermal injury secondary to trauma or surgery results in a phase of wound healing, involving an inflammatory response, resolution and repair, leading to asymptomatic scars or problematic scarring. The type of scarring in adults is therefore variable.…”

Section: Introductionmentioning

confidence: 99%

Scar satisfaction and body image in thyroidectomy patients: prospective study in a tertiary referral centre

Sethukumar

Awad

et al. 2017

J. Laryngol. Otol.

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Background: This study is the first to evaluate scar satisfaction and body image in thyroidectomy patients using validated assessment tools.Methods: A total of 123 thyroidectomy patients were recruited over 8 months. Both patients and clinicians completed assessment tools that included: the Manchester Scar Scale (to measure scar perception), Dysmorphic Concern Questionnaire (to assess body image), Body Dysmorphic Concern Questionnaire (to screen for body dysmorphic disorder) and EQ-5D (to measure life quality). A separate image panel comprising experts and nonexperts assessed 15 scar photographs. The results were analysed using non-parametric descriptive statistics.Results: Poor body image was associated with poor scar perception (ρ = 0.178, p = 0.05). Poor life quality correlated with poor scar perception (ρ = −0.292, p = 0.001). Scar length did not affect scar perception. Prevalence of body dysmorphic disorder among patients was found to be 8.94 per cent, which is higher than general population rates.Conclusion: Negative body image and life quality impact negatively upon scar perception.

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Scar Formation: The Spectral Nature of Fetal and Adult Wound Repair

Cited by 154 publications

References 36 publications

Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts

Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts

Treatment Outcome in Cleft Lip and Palate: Issues and Perspectives

Scar satisfaction and body image in thyroidectomy patients: prospective study in a tertiary referral centre

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