Tiam Mana Saffari

241 GENERAL DISCUSSION 11 the main objective for Part I: Does augmentation of nerve allografts with angiogenesis improve revascularization and subsequently nerve regeneration? First, the SIEF f lap increases vascularity which precedes nerve regeneration. Enhanced vascularity in the nerve graft was objectively measured using micro CT, photography, gene expression, immunof luorescence, and subjectively scored after immunohistochemical staining. The literature review, presented in Chapter 2 , suggests that angiogenesis precedes the repair of damaged nerves and is therefore in line with this hypothesis. Second, the SIEF flap diminishes nerve fibrosis, leading to enhanced nerve regeneration. The N-ratio presents the number of axonal sprouting and maturation of the regenerating nerve and a low N-ratio could be indicative of a relatively larger amount of fibrous tissue 44 . A significant lower N-ratio was found in nerve allografts, compared to allografts augmented with angiogenesis and nerve autografts. In Chapter 2 , it was presented that prolonged denervation time leads to intraneural fibrosis and core necrosis which negatively affects the nerve regeneration process 45 . The SIEF flap is found to not solely improve revascularization, but also to decrease graft ischemic time, subsequently impeding necrosis 46 . Taken together with the gene expression results described in Chapter 6 , the hypothesis could be made that a well vascularized bed, provided by the SIEF flap, suppresses nerve fibrosis. However, more extensive research is needed to further evaluate perineural scar formation and its effect on nerve regeneration. The future perspectives will be presented later in this chapter. In conclusion, evidence is provided that decellularized nerve allografts could be augmented with angiogenesis through the adipofascial SIEF flap, which provides a well vascularized bed for the nerve graft. This well vascularized bed stimulates a broad spectrum of paracrine actions, not solely induced by the secretion of VEGF, providing an anti-inflammatory microenvironment. This environment is suggested to enhance revascularization of the nerve graft, diminish nerve fibrosis and subsequently improve nerve regeneration.