Tiam Mana Saffari

228 CHAPTER 10 and scarring, subsequently resulting in improved diffusion to meet the demands of cellular metabolism 24,30,31 . The interaction between stem cells and vascularity remains complex and has not been thoroughly investigated. The organization of vessels in reconstructed nerves has been of interest. Only few studies have explored the 3D microvasculature of peripheral nerves 27,32-35 , emphasizing the necessity for imaging of nerve revascularization in conjunction with nerve reconstruction after trauma. It has been suggested that the amount of revascularization is enhanced at the sites of nerve coaptation in response to the acute hypoxia during nerve trauma 35,36 . Macrophages play an important role as sensors of hypoxia to induce angiogenesis during this process 37 . In addition, vessels away from the coaptation sites were found to be more organized and less frequently branched 35 . This is in line with our results, specifically in the nerve allografts that have been wrapped with a SIEF flap that was combined with undifferentiated MSCs. Blood vessels are found to provide directionality to Schwann cell movement and may therefore play a guidance role to neuronal precursors to enhance nerve regeneration 37,38 . Detailed evaluation of nerve angioarchitecture to the capillary level using 3D-skeletonization and its further analysis provided in this paper contributes to understanding of vessel organization. Although the interpretation of the macroscopic images suggests that larger diameter longitudinally running vessels are seen in autografts and controls (Figure 2), the vessel distribution analysis states differently and shows that nerve graft groups wrapped within the pedicled SIEF flap result in larger diameters of vessels (Figure 5). This incongruence may be reconciled in a few ways. First, the macroscopic images are depicted longitudinally, not providing visual insight into the lumen diameters of the vessels. Second, the volume of vessels (Figures 4A and 5A) depict the volume of vessel segments prior to its sprouting into a new segment. Although the measured volume segments of groups receiving surgical angiogenesis are comparable to or higher than controls and autografts, these account for a smaller portion in terms of percentage. Third, the vessel distribution analysis solely analyzes the provided 3D-skeleton without correcting for the total quantified vascular volume. This suggests that the evaluated spatial distributions need to be interpreted independently from the total volume to overcome a distorted picture of data.