Abstract
The efficient healing of skin wounds is crucial for securing the vital barrier function of the skin, but pathological wound healing and scar formation are major medical problems causing both physiological and psychological challenges for patients. A number of tightly coordinated regenerative responses, including haemostasis, the migration of various cell types into the wound, inflammation, angiogenesis, and the formation of the extracellular matrix, are involved in the healing process. In this article, we summarise the central mechanisms and processes in excessive scarring and acute wound healing, which can lead to the formation of keloids or hypertrophic scars, the two types of fibrotic scars caused by burns or other traumas resulting in significant functional or aesthetic disadvantages. In addition, we discuss recent developments related to the functions of activated fibroblasts, the extracellular matrix and mechanical forces in the wound environment as well as the mechanisms of scarless wound healing. Understanding the different mechanisms of wound healing is pivotal for developing new therapies to prevent the fibrotic scarring of large skin wounds.
Highlights
Intact healthy skin protects the body from outside threats; proper wound healing is an essential process in response to tissue damage[1,2,3]
In keloids, the numbers of CD301b+ macrophages and CD26+ adipocyte precursors (APs)-derived myofibroblasts are increased[45]. Another recent study showed that, during lung fibrosis, cadherin-11 mediates the adhesion between macrophages and myofibroblasts, promoting the activation of myofibroblasts and supporting their activity by targeting the macrophage-produced TGFβ to myofibroblasts[46]. These results suggest that the presence of distinct myofibroblast populations in different fibrotic microenvironments provides possibilities for targeting specific subpopulations of cells in anti-fibrotic therapies aiming at scarless wound healing
Scar tissue is formed mainly of fibrillar collagen produced by myofibroblasts
Summary
Intact healthy skin protects the body from outside threats; proper wound healing is an essential process in response to tissue damage[1,2,3]. Chronic inflammation of the dermis and uncontrolled function of activated connective tissue cells, myofibroblasts, may lead to abnormal overgrowth of the scar, resulting in a hypertrophic scar or a keloid with an excess of ECM proteins[6] (Figure 1) These two pathological types of scars have a different aetiology and unique and distinct structural and molecular characteristics, as will be discussed below in more detail. A recent comparison of human hypertrophic scars with normally healing scars showed increased and persistent expression of the TGFβ3 gene; surprisingly, there was no difference in TGFβ1 expression[29] This result conflicts with the view of differing TGFβ signalling between adult and foetal wounds and could partly explain the failure of TGFβ3 to prevent fibrosis in clinical trials[1,9,21,47,57]. Palatal and gingival wounds have been reported to heal without scarring in one study but another study reported rigid scar formation in palatal wounds[7]
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