Toward understanding scarless skin wound healing and pathological scarring

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.

Keywords: extracellular matrix; fibrosis; hypertrophic scar; keloid; myofibroblast; wound healing.

Figure 1.. Foetal and oral wound healing and different types of fibrotic skin scars.

A schematic drawing showing the structures of normal skin, scarless foetal and oral wounds, and the two main types of fibrotic cutaneous scars. The wound area is depicted with a dashed line. Foetal and oral wound healing share many characteristics. For example, these wounds contain a low number of myofibroblasts and extracellular matrix (ECM) does not accumulate in the wound bed. In addition, the inflammatory reaction is weak, which is manifested here by the low number of inflammatory cells in the wound. In oral wounds, saliva offers a humid environment with microbes, which is suggested to promote oral wound healing. The hypertrophic scar is limited to the area of the original wound and contains plenty of contracting myofibroblasts, which adhere to ECM via focal adhesion-like structures. Thin collagen fibres in the ECM are orientated in parallel to the cutaneous epithelia (insert). The keloid scar transcends the edges of the wound and extends into the surrounding skin. The inflammatory reaction is strong, dermal fibroblasts proliferate actively and thick hyalinised collagen bundles are orientated randomly (insert). Chronic inflammation persists, and angiogenesis is active in the keloids.