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.     

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.     

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.     

Inverted-U parascapular flap for the treatment of axillary burn scar contracture

In this paper we report the technique of using an inverted-U parascapular flap for treating axillary scar contracture. The advantages of using this inverted-U flap are that it is possible to close the donor site by primary suturing, it is possible to cover a large skin defect, and it is possible to construct either a cavity or a swelling in the skin-defect region.     

Molecular mechanism of myofibroblast formation and strategies for clinical drugs treatments in hypertrophic scars

Hypertrophic scars (HTS) commonly occurred after burn and trauma. It was characterized by the excessive deposition of extracellular matrix with the inadequate remodeling, which could result in severe physiological and psychological problems. However, the effective available prevention and treatment measures were still limited. The main pathological feature of HTS was the excessive formation of myofibroblasts, and they persist in the repaired tissue. To better understand the mechanics of this process, this review focused on the characteristics and formation of myofibroblasts, the main effector cells in HTS. We summarized the present theories and opinions on myofibroblasts formation from the perspective of related signaling pathways and epigenetic regulation, such as DNA methylation, miRNA/lncRNA/ceRNA action, histone modification, and so forth for a better understanding on the development of HTS. This information might assist in developing effective experimental and clinical treatment strategies. Additionally, we also summarized currently known clinical strategies for HTS treatment, including traditional drugs, molecular medicine, stem cells, and exosomes.