Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation.
SCOPE AND SIGNIFICANCEThis article reviews the extracellular matrix (ECM) and its remodeling during normal cutaneous wound healing and scar formation, and the differential response of the components of the ECM and their role in pathological (hypertrophic and keloid) cutaneous scar formation. This review focuses on the major players involved in the irregular ECM production as being; fibroblasts and their immature counterparts, myofibroblasts; collagens; transforming growth factor (TGF)-b, which controls the production of collagens; proteoglycans and matrix metalloproteinases (MMPs). We also highlight the complexity of interactions occurring in the ECM of skin during (ab) normal scar formation.
TRANSLATIONAL RELEVANCEAbnormal ECM, particularly abnormal collagen remodeling and reorganization, accounts for one of the most important contributing factors to abnormal scarring. Identification of the exact ECM molecules involved in causing abnormal scarring is likely to provide a future treatment target. This may be achieved by promoting the correct balance in collagen ratios or by directly targeting the production of collagen. Overall, a better understanding of the exact roles of ECM components in scarring will help us to produce therapeutic agents to prevent and treat hypertrophic and keloid scars.
CLINICAL RELEVANCEThere ...