Joris van Dongen

185 tSVF as a treatment for scar remodeling INTRODUCTION Wound healing is the primary response of the body to a tissue or skin defect in order to regenerate a first mechanical barrier for pathogens. Initial, wound healing is a physiological reaction following consecutive phases: hemostasis, inflammation, proliferation and remodeling. 1 During hemostasis, a fibrin clot is formed to stop bleeding and retain cytokines and growth factors released from platelets e.g. platelet derived growth factors (PDGF), transforming growth factor- β (TGF- β ), fibroblast growth factors (FGF),vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF). 2-4 These factors initiate the transition from hemostasis to inflammation by attracting macrophages and neutrophils. During the inflammation phase, granulocytes and macrophages phagocytose debris and invading pathogens and thus from a barriers to protect the wound. When all contaminating bacteria are removed, neutrophils start to disintegrate and macrophages shift from type 1 to type 2 phenotype allowing to initiate the proliferative phase, which is characterized by fibroblast proliferation, migration and differentiation into myofibroblasts. 5,6 Then, these (myo)fibroblasts start to synthesize collagen and play a key role inwound contraction. 7 In the final remodeling or fibrotic phase, the ratio of type I and type III collagen is reversed from more type III to more type I with stronger crosslinking of collagen fibers. 8 Ideally, these consecutive and overlapping phases result in scarless regeneration of the skin. However, several factors contribute to pathological scar formation after wound healing e.g. chronic inflammation or large wound size causing excessive myofibroblast invasion over-producing large amounts of collagen. This excessive collagen deposition yields stronger cross-linking density which stimulates myofibroblasts to further contract and secrete more collagen. In physiological wound healing, fibrotic tissue is replaced by healthy tissue before fibrotic initiates such a positive feedback loop. 9,10 Significant pathological wound healing is often caused by diseases and disorders e.g. diabetes mellitus, peripheral arterial disease or burn wounds. Although, inflammation is important for proper wound healing, a chronic state of inflammation decrease vascularization and causes necrosis such as seen in diabetic ulcers. Till now, no standard evidence-based treatment is available to increase normal ideal wound healing by stimulating simultaneously multiple wound healing related processes e.g. angiogenesis, immunomodulation and matrix remodeling. However, recent developments have shown that stromal vascular fraction (SVF) of adipose tissue, which is a heterogenous mixture of cell types containing a plethora of growth factors and cytokines, should be able to stimulate the aforementioned wound healing related processes. 11-13 Traditionally, enzymatically, prepared SVF consist of adipose