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A novel tissue engineered nerve graft (TENG) was used for the first time to bridge a 60 mm long nerve gap in a dog sciatic nerve and achieved satisfactory results.

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Myelin plays a crucial role in axon function recovery following nerve damage, and the interaction between Schwann cells (SCs) and regenerating axons profoundly affects myelin formation. Eph receptor A4 (EphA4), a member of the Eph tyrosine kinase receptor family, regulates cell-cell interactions via its ligand ephrins. However, our current knowledge on how EphA4 regulates the formation of myelin sheaths remains limited. In order to explore the roles of EphA4 in myelination in the peripheral nervous system, we used a combination of (1) a co-culture model of dorsal root ganglion (DRG) explants and SCs, (2) a SC differentiation model induced by db-cAMP, and (3) a regeneration model of crushed sciatic nerves in rats. Our results demonstrated that EphA4 inhibited myelination by inhibiting SC differentiation and facilitating SC proliferation in vitro. The in vivo experiments revealed that EphA4 expression in SCs is upregulated following nerve crush injury and then downregulated during remyelination. Moreover, silencing of EphA4 by siRNA or overexpression of EphA4 by genetic manipulation can accelerate or slow down nerve remyelination in crushed sciatic nerves. Taken together, our results suggest that EphA4 may negatively regulate myelination by abrogating SC differentiation.

Potential interaction between immune response and axonal regeneration has recently attracted much attention in peripheral nervous system (PNS). Previously, global mRNA expression changes in proximal nerve segments were profiled and merely focused on the differentially change of the key biological processes. To further uncover molecular mechanisms of peripheral nerve regeneration, here we focused on the interaction between immune response and axonal regeneration that associated with specific molecular pathways and interactive networks following sciatic nerve transection. To offer an outline of the specific molecular pathways elaborating axonal regeneration and immune response, and to figure out the molecular interaction between immune response and axonal regeneration post-sciatic nerve transection, we carried out comprehensive approaches, including gene expression profiling plus multi-level bioinformatics analysis and then further experimental validation. Alcam, Nrp1, Nrp2, Rac1, Creb1, and Runx3 were firstly considered as the key or hub genes of the protein-protein interaction (PPI) network in rat models of sciatic nerve transection, which are highly correlated with immune response and axonal regeneration. Our work provide a new way to figure out molecular mechanism of peripheral nerve regeneration and valuable resources to figure out the molecular courses which outline neural injury-induced micro-environmental variation to discover novel therapeutic targets for axonal regeneration.