The efficacy of combining a vascularized biogenic conduit and a decellularized nerve graft in the treatment of peripheral nerve defects: An experimental study using the rat sciatic nerve defect model

Background

Although decellularized nerve grafts are often used as a bridging material in nerve defect repair, the lack of perfusion support in this procedure limits the regeneration capacity. To address this, we applied vascularized biogenic conduits, which are fibrous membranes prefabricated around the silicone rod that contain rich vascularity and macrophages, to nerve defect repair procedures using decellularized nerve grafts. The purpose of this study is to investigate the capacity of combining a vascularized biogenic conduit and a decellularized nerve graft for peripheral nerve regeneration using a 10-mm nerve defect model in rats.

Materials and Methods

Sixteen adult male rats (F344 rats, 10–12 weeks, 200–250 g) were used in this study. For the prefabrication of vascularized biogenic conduits, a silicone rod was transplanted next to the sciatic nerve. After 8 weeks, this silicone rod was enveloped in connective tissue, called a vascularized biogenic conduit. The first rat was used to investigate the histological characteristics of vascularized biogenic conduits through immunofluorescence studies. The remaining 15 rats were divided into three groups to evaluate the efficacy of the combination of a decellularized nerve graft and a vascularized biogenic conduit: a decellularized nerve graft (DNG) group, a decellularized nerve graft with a vascularized biogenic conduit (DNG-w-VBC) group, and an autologous nerve graft (ANG) group. Eight weeks after nerve graft surgery, the assessment results of both functional recovery (electrophysical studies and target muscle atrophy) and morphological recovery (total number, diameter, and myelin thickness of the regenerated axons) of the regenerated nerves were examined.

Results

Immunofluorescence studies revealed that the VBC contains extracellular matrix, vascular tissue, and macrophages. The results of the DNG-w-VBC group were superior to the DNG group in electrophysiological studies (CMAP; 6.29 ± 0.80% vs. 4.02 ± 3.35%, MNCV; 50.6 ± 8.4% vs. 25.7 ± 15.6%, p < .05, respectively), regenerated axon number (11,348 ± 812 vs. 7697 ± 2197, p < .05), and mean axon diameter (2.72 ± 0.33 μm vs. 1.64 ± 0.12 μm, p < .05).

Conclusions

Our study confirms that vascularized biogenic conduits supply vascularity and macrophages to nerve defect sites. Combining vascularized biogenic conduits with decellularized nerve grafts to treat nerve defects offers superior functional and morphological recovery of regenerated axons.

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