Current concepts related to hypertrophic scarring in burn injuries

Abstract

Scarring following burn injury and its accompanying aesthetic and functional sequelae still pose major challenges. Hypertrophic scarring (HTS) can greatly impact patients' quality of life related to appearance, pain, pruritus and even loss of function of the injured body region. The identification of molecular events occurring in the evolution of the burn scar has increased our knowledge; however, this information has not yet translated into effective treatment modalities. Although many of the pathophysiologic pathways that bring about exaggerated scarring have been identified, certain nuances in burn scar formation are starting to be recognized. These include the effects of neurogenic inflammation, mechanotransduction, and the unique interactions of burn wound fluid with fat tissue in the deeper dermal layers, all of which may influence scarring outcome. Tension on the healing scar, pruritus, and pain all induce signaling pathways that ultimately result in increased collagen formation and myofibroblast phenotypic changes. Exposure of the fat domes in the deep dermis is associated with increased HTS, possibly on the basis of altered interaction of adipose-derived stem cells and the deep burn exudate. These pathophysiologic patterns related to stem cell-cytokine interactions, mechanotransduction, and neurogenic inflammation can provide new avenues of exploration for possible therapeutic interventions.

Figure 1

The dermal cone/fat dome structure and its role in burn-related HTS pathogenesis. Burn wounds that reach the depth of the fat dome structure are more prone to develop HTS. The fat dome is thought to be a main reservoir of ADSCs. Interactions of the burn wound fluid with ADSCs shape the healing process, and in some instances direct it down the HTS pathway. Via chemokine CCL27, burn wound fluid influences residual ADSCs in the fat dome to secrete a variety of growth factors that promote collagen synthesis, angiogenesis and granulation tissue formation in the wound bed. Additionally, fat dome ADSCs are one of the putative sources of aggressive myofibroblasts that are highly characteristic of HTS. Abbreviations: HTS - hypertrophic scarring; ADSCs - adipose-derived stem cells; VEGF - vascular endothelial growth factor; PDGF - platelet-derived growth factor; bFGF - basic fibroblast growth factor; EGF - epidermal growth factor; KGF - keratinocyte growth factor; TGF-β - transforming growth factor beta; CCL27 - chemokine CCL27. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]