Joris van Dongen

16 Chapter 1 Lipofilling and skin rejuvenation In 2006, Coleman was the first to describe that lipofilling was more than a permanent filler. 57 Colemandescribed that the overlying skin of transplanted adipose tissue showed signs of improvement e.g. less scarring caused by acne and decreased pores size. 57,58 He surmised that the observed skin rejuvenation was facilitated by the presence of ASCs in fat grafts. 57 . In 2013, Tonnard et al. showed three clinical cases with reduced dark coloration of the lower eyelid and reduced number of wrinkles of the décolleté and perioral after treatment of Nanofat. 59 This was the first case report showing skin rejuvenation after the use of emulsified lipoaspirate. Since the publication of the Nanofat procedure, an increase interest in facial skin rejuvenation using regenerative components of adipose tissue e.g. SVF has been. 59-69 In most studies, SVF has been used as additive to lipofilling to increase the ratio of regenerative cells/per ml of lipoaspirate injected in facial planes.The rationale behind SVFenriched lipofilling is to enhance skin rejuvenation. However, most of these studies lack a proper study design with objective outcomes. Thus far, no solid conclusion could be made whether SVF as additive to facial lipofilling or as monotherapy is effective for skin rejuvenation, although a large commercial market already exists. AIM AND OUTLINE OF THE THESIS The aimof studies described in this thesis is to design and develop a new intra-operative mechanical isolation procedure to isolate SVF; to evaluate the skin rejuvenative effect of SVF on a decreased skin quality caused by aging and scarring using our newly developed mechanical isolation procedure to isolate SVF. Using in vitro experiments, this thesis aims to identify the regenerative components of SVF responsible for stimulating important processes related to skin rejuvenation. To date, the Gold standard for SVF isolation is enzymatic isolation. However, an increasing number of countries forbids by legislation the use of enzymes to manipulate tissue. To bypass legislation, a growing number of alternative mechanical isolation procedures are being developed. Chapter 2 comprises a systematic review of the available intra-operative enzymatic and mechanical isolation procedures. In this systematic review, procedure characteristics and composition of isolated SVF are compared. Chapter 3 describes the development and validation of our own developed mechanical isolation procedure to isolate SVF, the so-called Fractionation of Adipose Tissue (FAT) procedure. After several years of gaining experience using the FAT procedure, minor practical issues were discovered which led to development of a new version of the FAT procedure. Chapter 4 describes the validation of the latest