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Revascularization Patterns Of Nerve Allografts In A Rat Sciatic Nerve Defect Model
Tiam M. Saffari, MD, Femke Mathot, MD, Allen T. Bishop, Prof, MD, Alexander Y. Shin, Prof, MD.
Mayo Clinic, Rochester, MN, USA.

PURPOSE: The outcome of tissue transplantation critically depends on the revascularization process and consequently regeneration of nerve is similarly dependent on this process. The specific patterns of revascularization of allograft nerves after addition of vascularization remain unknown. The aim of this study was to determine the revascularization patterns of optimized processed allografts (OPA) after surgically induced angiogenesis to the wound bed in a rat sciatic nerve model.
METHODS: In 51 Lewis rats, ten mm sciatic nerve gaps were repaired with (i) autografts, (ii) OPA and (iii) OPA wrapped in a pedicled superficial inferior epigastric artery fascia flap (SIEF) to provide vascularization to the wound bed. Nerves harvested from Sprague Dawley rats served as donors and were processed using a five-day decellularization protocol described by Hundepool et al (2017). At two, 12 and 16 weeks, the vascular volume and vascular surface area in nerve samples were measured using micro CT and photography, respectively. To describe the revascularization patterns in various parts of the nerve, cross-sectional images from micro CT imaging were obtained for the 12- and 16 week survival periods. The length of the nerve between both anastomoses was divided into three equal sections: proximal, mid and distal. Cross-sectional images were divided into three equally concentric rings.
RESULTS: Starting at two weeks, vascularization consisting of a mesh-network occurred from both host stumps in nerve allograft and SIEF samples, leaving the middle part avascularized. Over time, the sprouted vessels reached to the middle parts of the nerve, more evident from the proximal than from the distal end. In nerve autografts, longitudinal running vessels were recognized, comparable to control (Figure 1 and 2). At two weeks, the vascular volume of SIEF nerves was comparable to control (P=0.1). The vascular surface area in SIEF nerves was superior to other groups (P<0.05). At 12 weeks, vascularity in SIEF nerves was significantly higher than allografts (P<0.05) and superior compared to all other groups (P<0.001) at 16 weeks. SIEF nerves had a significantly increased number of vessels compared to allografts alone in the proximal (P<0.05) and mid-section of the graft (P<0.05). The number of vessels counted in all three rings was highest in SIEF nerves in the proximal and mid-section of the graft, compared to allografts. In the distal section of the nerve, a trend towards a higher number of vessels was seen in SIEF nerves, however, this was not significant.
CONCLUSION: Addition of surgical angiogenesis to the wound bed greatly improves revascularization. It was demonstrated that revascularization occurs primarily from proximal to distal (proximal inosculation) and not from both ends as previously believed and confirms the theory of centripetal revascularization.


Figure legends: Micro CT and photography images of control nerve(A), autograft(B), OPA(C) and OPA+SIEF(D).


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