Tiam Mana Saffari

19 GENERAL INTRODUCTION 1 allografts in vitro and evaluate their survivability in the rat. Rotation of tubes in which decellularized nerve allografts were combined with MSCs, allowed for adherence of MSCs to the nerve, without inducing trauma to the nerve or MSCs. After 12 to 24 hours of dynamic seeding, seeding efficiency was found to be approximately 80% and cells were distributed homogeneously over the surface of the grafts 44 . When placed in vivo , labeled MSCs could be detected up to 29 days, without any migration of cells to surrounding tissues 45 . Differentiation of MSCs into Schwann cell-like cells, to induce Schwann cell neuroregenerative properties, was successfully validated and found to enhance secretion of various angiogenic factors and neurotrophic factors (Figure 4B, rectangle 2) 46,47 . Figure 4B. Flowchart of historical background of this thesis. This thesis is part of an ongoing re - search line and builds on the results of previously conducted research that has focused on seeding the decellularized nerve allografts with stem cells. Moreover, stem cells were differentiated into Schwann cell-like cells to resemble Schwann cell properties (rectangle 2). With permission of the Mayo Foundation, Copyright Mayo Foundation. All rights reserved. Augmenting decellularized allograft with angiogenesis Vascularization is one of the great challenges faced in nerve reconstruction, especially in nerve autograft substitutes such as nerve allografts that have been processed and do not contain living cells 48 . In nerve allografts, revascularization needs to be achieved to ensure cellular survival and avoid central necrosis. This has been a longstanding challenge in nerve grafts with large diameters and in long defects 48,49 . The first free vascularized nerve graft (VNG) was reported in 1976 and indicated in cases lacking well-vascularized beds. VNGs have the advantage of overcoming a period of ischemia and ensure continuous nutrition of the graft, which is suggested to prevent intraneural fibrosis. However, evidence for their clinical superiority has remained inconclusive 50 .