Portion of the nerve grafts the number of myelinated axons in the group was significantly higher

In the LCCH group at the predefined time points after surgery. In addition, the number of FG-labeled motoneurons and sensory neurons in the L-CCH+OW group was as well significantly higher than that in the L-CCH group. These mean that the “axon-SC dance” may be supported to some extent by application of omentum, and more neurons may be supported survival and more neurites may be generated by regenerating neurons. The introduction of omentum-wrapping led to improved motor functional recovery. The amplitude of CMAP as well as the histological appearance of target muscles reflects the reinnervation of distal target muscles. In the present study, both the amplitude of CMAP and the histological appearance of gastrocnemius muscles in the L-CCH+OW group were significantly higher than those in the L-CCH group. This indicates that more axons may successfully proceed through the omentum-wrapped scaffold into the distal stumps and reinnervate target muscles, therefore the atrophy of target muscles was partially reversed. In addition, walking track analysis was performed and scored by SFI which provides a reliable measure for evaluating the recovery of motor function. In the present study, the SFI values were in the similar range between the L-CCH+OW and the Reversine autograft groups. Nerve autograft is the most frequently used positive control in studies of nerve defects reconstruction. In many previous studies, incorporating neurotrophic factors or introducing supportive cells into nerve scaffolds can achieve a similar performance to nerve autograft in promoting nerve regeneration and functional recovery. Therefore, it is reasonable to speculate that the efficacy of the omentum-wrapped L-CCH scaffold in promoting nerve regeneration might be further improved by introducing supportive cells and incorporating neurotrophic factors into the scaffold. It is reported that an omentum on contact with a foreign body or activated by injury expands rapidly in size and mass, and the tissue growth is paralleled by the increase in blood vessel density, thereby supporting increased angiogenesis. Vascular endothelial growth factor is the primary angiogenic factor produced by omentum, which may facilitate the growth of new blood vessels and accelerate tissue repair. In the present study, a significantly higher blood vessel density was observed in the L-CCH+OW group compared with that in the LCCH group. Further investigation found that the protein levels of VEGF in the L-CCH+OW group were significantly higher than those in the L-CCH group at 2 and 4 weeks after surgery, which might be responsible for the formation of higher blood vessel density, thereafter providing adequate blood supply to the regenerating axons and consequently resulting in improved nerve regeneration and functional recovery. In addition, VEGF has been reported to have neurotrophic and mitogenic activity on growth cones and SCs, hence stimulating axonal outgrowth, survival and proliferation of SCs independent of the increased vascularization. Therefore, the angiogenic activity and neurotrophic property of VEGF might contribute to the beneficial effect of omentum on axonal regeneration and functional recovery. Brain-derived neurotrophic factor and nerve growth factor hold great potential in promoting nerve regeneration by providing an appropriate environment for axonal outgrowth.

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