YR/DFO@DCNT functionalized anisotropic micro/nano composite topography scaffolds for accelerating long-distance peripheral nerve regeneration

Anisotropic topography could effectively regulate the orientation growth of nerve fibers and promote nerve regeneration process, however, their effect on repairing long-distance peripheral nerve injury is not comparable to autologous grafts and should be further enhanced. In this study, an anisotropic micro/nano composite topography scaffolds containing functionalized multi-walled carbon nanotube(CNT) with YIGSR (YR) and deferoxamine (DFO) was developed by combining use of micro-molding and electrospinning technologies, which is the so-called micro-molded electrospinning (MME). The scaffolds displayed composite topology structure, with randomly-oriented nanofibers and parallel-oriented micro-ridge/grooves, enhanced mechanical properties, and good photo-thermal responsiveness, and could guide the orientation growth of Schwann cells, promote the axon elongation of dorsal root ganglion in vitro. The in vivo evaluation indicated that the developed scaffolds obviously enhanced vascularization, inhibited inflammatory reaction and effectively accelerated the long-distance nerve regeneration with good functional recovery. Further on, the transcriptome sequencing revealed that the YR/DFO@DCNT functionalized anisotropic micro/nano composite scaffolds could upregulate the expression of MET, MPZ and TAZ, which were closely associate with neural cell migration and survival, myelination and cytoskeleton rearrangement for axon elongation and nerve regeneration. Altogether, the anisotropic micro/nano composite topography incorporated with YR/DFO@DCNT by MME may represent a promising strategy for repairing peripheral nerve injury.