Angiogenesis and Axonal Elongation in Decellularised Nerve Grafts Depend on the Surrounding Vascular Environment

Background: Decellularised nerve transplantation has limited therapeutic efficacy for peripheral nerve injuries. In this study, we tested the hypothesis that nerve regeneration can be promoted by increasing blood circulation to the decellularised nerve through the surrounding blood-flow environment. Methods: We transplanted 20 mm decellularised nerves into sciatic nerve defects in Sprague-Dawley rats (female, 12 weeks old). In the intramuscular group, the decellularised nerve was implanted into the biceps femoris muscle and covered with the muscle to provide blood circulation. In the avascular group, the decellularised nerve was sutured to the sciatic nerve and the surrounding nerve bed was cauterised to create a non-bleeding field. In the intramuscular without repair group, the decellularised nerve was implanted in the biceps femoris muscle, but not sutured to the sciatic nerve. Axonal elongation and angiogenesis were evaluated immunohistochemically using anti-neurofilament, anti-S100 and anti-CD31 antibodies in sagittal and transverse sections of the nerve 3 weeks later. Results: In the intramuscular group, the number of neurofilaments per unit area and S100 were higher than those in the other groups (p < 0.05). CD31 staining was predominant in the intramuscular group. Axial images of the nerves confirmed the localisation of CD31-positive cells, and positive cells were found in the centre of the decellularised nerves in the intramuscular group. Conclusions: Decellularised nerve grafts wrapped with vascular-rich tissue promoted nerve regeneration by enhancing angiogenesis in transplanted nerve grafts and preventing ischemia in the centre of the nerve graft.