Tiam Mana Saffari

147 FUNCTIONAL MOTOR RECOVERY OF ANGIOGENESIS OF NERVE ALLOGRAFTS 7 tool of functional recovery. Muscle force may therefore be a parameter that expresses functional recovery better than muscle mass or cross-sectional area 32 . Histological parameters did not result in differences between groups with respect to axon count, axon area and myelin area. A low N-ratio, seen in allografts at 12 weeks, could be indicative of a relatively larger amount of fibrous tissue 49 , compared to SIEF and autografts. This indicates that provision of vascularization to nerve allograft wound bed may decrease fibrosis of the nerve. This is clearly visualized with the expression of CD34 that indicated vascularity in allografts predominantly in the outer layer, while the SIEF flap enhanced vascularity with abundant distribution throughout the nerve graft, reaching the core of the nerve. As few experimental studies have evaluated VNGs or addition of adipofascial flaps 15,20 , it remains difficult to compare findings. A previous study has found that at three weeks post-operatively, fat graft wrapping around the nerve coaptation increased lymphocyte infiltration rates and macrophage migration; processes that are involved in the early neural regeneration period 15 . This previous study did not find improved neovascularization after fat graft wrapping 15 , possibly due to the chosen end-point and limitations in evaluating vascularity. Despite this study, little has been reported on the effect of adipose tissue placed around nerve reconstructions. It is assumed that a pedicled adipofascial flap containing adipose tissue and a vascular bundle improves revascularization of the nerve allografts through excreted angiogenic factors and nutrition, provided by the vascular bundle and stem cells in the adipose tissue, while preventing fibrosis and core necrosis 10,50,51 . Blood vessels have been found to precede neural regeneration and stimulate injured axons and non-neuronal cells to produce a supportive microenvironment after nerve injury 35,52,53 . Moreover, capillary changes as well as Schwann cell migration suggest axon growth 54 , explaining improved early functional recovery. Although surgical angiogenesis to the allograft continued increasing vascularity in the graft at 16 weeks, functional outcomes did not improve at this time point. This raises the possibility of a ceiling effect of vascularity on nerve regeneration. Addition of other factors combined with surgical angiogenesis, such as stem cells, may be another potential strategy to further improve regeneration. The importance of stem cells relies on their ability to secrete various growth factors, such as neurotrophic factors to stimulate myelin formation, and its potency is emphasized to be influenced by its microenvironment (i.e. paracrine properties) 55 . Adipose tissue,