Joris van Dongen

160 Chapter 7 Influence of lipofilling in scars at the tissue level Microscopically, scars display a loss of rete ridges, sebaceous glands and hair follicles. Also, they are characterized by increased dermal and epidermal thickness 46,47 . The epidermal thickening is caused by excessive proliferation of keratinocytes. In the dermis, the thickening is causedbyexcessiveECMproductionbymyofibroblasts,mainly consisting of collagen type I 48 . Not only is there an increase in the amount of collagens, but also in the collagen fiber thickness, maturation and degree of disorganization 46,47 . Even though there is an increase in the amount of ECM in scarring, some components of normal skin (e.g. elastin, decorin) are less abundant in scars 49 . In two patient studies, skin biopsies have been acquired before and after treatment of scars with lipofilling 8,29 , one study evaluating a complete series of biopsies from a single patient 8 . After lipofilling, the general structure of the skin improved, collagen was remodeled, and there was an increase in vascularization. In a large, placebo-controlled study, lipofilling in large burn scars was compared to saline injection 29 . In 96 patients, half of the scar was injected with saline (placebo or sham treated group), the other half was injected with lipoaspirate. Skin biopsies were taken and analyzed after three and six months. Overall, the histological structure of the scars returned near to that of normal skin: a better organization and alignment of collagen fibrils, better vascularization of the dermal papillae, less melanocytic activity in the epidermis and an increase of the amount of elastin fibers. On cellular level, there was an increase in cell divisions in the basal layer of the epidermis and Langerhans cells migrated downwards into this basal layer. Also, levels of pro-fibrotic factor Transforming Growth Factor beta 1 (TGF- β 1) and pro-angiogenic factors Vascular Endothelial Growth Factor (VEGF) decreased. In summary, histological improvement in scar appearance was noted in both studies, expressed as a plethora of changes on both histological as well as cellular level. However, why and how lipofilling results in the improvement of all these aforementioned aspects of scarring including pain reduction, remains to be elucidated. Animal studies In contrast to clinical studies thus far, experimental animal models have been able to demonstrate the mechanisms and influence of lipofilling on dermal scars, scar exterior and scar pain (Table 2).