Tiam Mana Saffari

236 CHAPTER 11 GENERAL DISCUSSION The study of peripheral nerve regeneration potential dates back to ancient times, with the first descriptions found in Galen’s writings in the second century A.D. 1 . Despite advancements in research and microsurgical techniques, complete motor recovery from peripheral nerve injuries and reconstruction is still rarely achieved. With regeneration proceeding at a rate of 1 mm per day, reinnervation of target neuromuscular junctions may take months and a prolonged delay may result in irreversible changes in the target muscle resulting in detrimental functional recovery 2-4 . Providing reconstruction options to meet the critical window of time, therefore, has remained a focus of research in 2021 and has led to the research question of this thesis: Does augmentation of nerve allografts with angiogenesis and stem cells improve revascularization and subsequently nerve regeneration? The discussion is divided in two parts: the role of angiogenesis (Part I) and the combined effect of angiogenesis and stem cells (Part II). Furthermore, future perspectives and research needed to translate these findings from bench to bedside are explored. PART I: THE ROLE OF ANGIOGENESIS IN NERVE REGENERATION In the 1980’s, several experimental and clinical studies investigated the effectiveness of adding vascularization to a nerve graft. Sensory and functional motor recovery results were conflicting when comparing vascularized nerve grafts (VNG) to non- vascularized nerve grafts (NVNG) 5-11 . To this end, the addition of vascular endothelial growth factor (VEGF) to nerve allografts was investigated in a rat sciatic nerve defect model. Unfortunately, VNGs face many technical obstacles and are indicated in large nerve defects to improve outcomes in complex and unique cases 12,13 . With no direct comparison to NVNGs, conclusions on the superiority of VNGs is only speculated and not proven. The overarching faced problem is that only case studies are available and no controlled studies exist that evaluate the provision of vascularization to the nerve bed. Transplantation of a nerve graft based on its arterial pedicle (VNG) is technically challenging and does not alter the tissue bed. The aim of Chapter 3 was to validate a surgical technique that provides angiogenesis to the nerve bed. The pedicled superficial inferior epigastric artery fascial (SIEF) flap in the rat was