**5. Chronic inflammation and burn scar formation**

Burn injuries are often characterised by debilitating hypertrophic scarring, often requiring revisionary surgery (**Figure 3**). In children, scar formation following burn injury is of particular concerns, as the growing child will be restricted by non-elastic scars, which when occurring over moving joints can become functionally restrictive [59]. This is due to an excessive synthesis and deposition of ECM alongside the reduced degradation and remodelling of tissue, leading to the dense formation of collagen in long bundles rather than the normal basket weave formation [60]. Scars are also characterised by an absence of skin appendages such as hair follicles, sweat glands and nerves, which results in functional deficiency, loss of ability to regulate body temperature and absence of sensation [61]. Due to the potentially large areas which may be affected by severe scarring following burn injury, the ability to reduce scar formation is of critical importance.

The link between the increased inflammatory response and the formation of scars is well established [61, 62]. It is clear that prolonged and/or excessive inflammation in the early stages of burn injury leads to excessive fibrosis and scarring [63]. In particular, the numbers of macrophages found within a wound at specific times of the healing cascade are associated with the level of fibrosis and scar formation observed [10]. Likewise, elevated TGF-β1 signalling is directly associated with increased collagen deposition and fibrosis within the healed wound

**Figure 3.** Post-burn hypertrophic scar on anterior chest wall. Reproduced from [59].

as well as myofibroblast over-activation and contracture formation [29, 30, 64]. As described earlier, both the pro-inflammatory macrophage phenotype and elevated TGF-β1 signalling seen in burn wounds contribute to the systemic complication of the immune response as well as this additional role in the formation of hypertrophic scars. There is clearly a very great need for the development of treatments which can control inflammation in burn wounds, to reduce the risk of SIRS and prevent excess scar formation, whilst maintaining the ability to fight infection.
