Tiam Mana Saffari

100 CHAPTER 5 9,20,21 . Inosculation results in endothelial-lined newly formed blood vessels starting from day three, without formation of vessels in the middle segment of the graft 9,22,23 . It is believed that the vessels in the mid-section are formed by ingrowth of blood vessels from the surrounding bed, starting by day six to eight 22 . The larger the grafts, the longer it takes to be completely revascularized, with risk of fibrosis and central necrosis 22 . Neovascularization is a complex process of critical importance involving endothelial cells, sprouting from the parent vessel, and releasing of growth factors, such as vascular endothelial growth factor (VEGF), a potent angiogenic factor required during tissue repair 6,24 . The predominant mechanism (centripetal versus bidirectional inosculation) of revascularization remains unknown. The findings in this study are in line with the theory that inosculation occurs prior to centripetal revascularization. At two weeks, early revascularization in nerve allografts occurred from both nerve stumps, but primarily from proximal to distal. In allografts wrapped in a pedicled flap, this amount of inosculation was greater, suggesting that an improved vascularized bed promotes longitudinal inosculation, in particular proximal inosculation. Favored proximal vascular advancement was also suggested by Chalfoun and colleagues using microvascular blood flow imaging 25 . This finding may support the fact that success of the nerve graft is partly affected by the length of the nerve graft 22 as a longer graft is subject to higher risk of necrosis in the mid to distal sections. Between autografts and control nerves a similar pattern of vascularization was seen, indicating that reestablishment of blood supply occurs along preexisting vascular channels 22,26 . In VNGs (vascularized nerve grafts), neovascularization is triggered in the first 72 hours as the blood flow is equal or greater than that in normal nerves suggesting to prevent early ischemia 22 . This is clearly seen in the increase in vascular volume of the revascularized allografts compared to the allografts at two weeks. The vascular volume represents the actual volume of vessels in the nerve, whereas the vascular surface area is more likely to be an estimation of vessels as a three dimensional structure is converted to a two dimensional structure. In small nerve samples, a high resolution of micro CT is crucial to identify the smallest vessels. When such a micro CT is not available, vascular surface areas can be used to clarify differences between experimental groups as similar trends between the vascular volume and vascular

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