The molecular mechanism of hypertrophic scar

Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder which often develops after thermal or traumatic injury to the deep regions of the skin and is characterized by excessive deposition and alterations in morphology of collagen and other extracellular matrix (ECM) proteins. HTS are cosmetically disfiguring and can cause functional problems that often recur despite surgical attempts to remove or improve the scars. In this review, the roles of various fibrotic and anti-fibrotic molecules are discussed in order to improve our understanding of the molecular mechanism of the pathogenesis of HTS. These molecules include growth factors, cytokines, ECM molecules, and proteolytic enzymes. By exploring the mechanisms of this form of dermal fibrosis, we seek to provide some insight into this form of dermal fibrosis that may allow clinicians to improve treatment and prevention in the future.     

Proteoglycans and collagenase in hypertrophic scar formation.

The collagen fibers of the nodules and whorl-like figures in hypertrophic scars are "coated" with proteoglycans, mainly chondroitin-4-sulfate. The latter was shown to prevent collagenase from breaking down collagen. This suggests that the presence of great amounts of chondroitin-4-sulfate in hypertrophic scars may contribute to the overabundance of collagen deposition which is characteristic of this abnormal healing process.     

Free radical involvement in hypertrophic scar formation

Hypertrophic scarring following thermal injury has become a major problem in Hong Kong. There is evidence that immunological and biochemical changes are associated with thermal injury, including pyridinoline crosslinks which are present in large quantities in hypertrophic scar, but the primary cause of hypertrophic scar formation still remains to be established. It has been reported that free radicals are assosciated with the formation of pyridinoline. In this study, attempts have been made to elucidate the involvement of free radicals in hypertrophic scar formation after thermal injury by determining the concentrations of Complement, free iron and pyridinoline crosslinks in collagen fibres. The results showed that the Complement activation product, C3d, was increased in the first week (i.e., day 7) postburn, indicating an acute inflammatory response. Free radicals, reported to be associated with the formation of pyridinoline crosslinks, and free iron content, were also found to have higher concentration in hypertrophic scar than in normal skin. The data suggest the involvement of free radical in hypertrophic scar formation. The observed increase in serum C3d concentration in about the first week indicates an acute inflammatory response to thermal injury. Both C3d and free iron concentrations (in vitro) are found higher in hypertrophic scar than in normal skin may suggest their roles in the generation of free radicals.