Potential cellular and molecular causes of hypertrophic scar formation

A scar is an expected result of wound healing. However, in some individuals, and particularly in burn victims, the wound healing processes may lead to a fibrotic hypertrophic scar, which is raised, red, inflexible and responsible for serious functional and cosmetic problems. It seems that a wide array of subsequent processes are involved in hypertrophic scar formation, like an affected haemostasis, exaggerated inflammation, prolonged reepithelialization, overabundant extracellular matrix production, augmented neovascularization, atypical extracellular matrix remodeling and reduced apoptosis. Platelets, macrophages, T-lymphocytes, mast cells, Langerhans cells and keratinocytes are directly and indirectly involved in the activation of fibroblasts, which in turn produce excess extracellular matrix. Following the chronology of normal wound healing, we unravel, clarify and reorganize the complex molecular and cellular key processes that may be responsible for hypertrophic scars. It remains unclear whether these processes are a cause or a consequence of unusual scar tissue formation, but raising evidence exists that immunological responses early following wounding play an important role. Therefore, when developing preventive treatment modalities, one should aim to put the early affected wound healing processes back on track as quickly as possible.