Anisotropically Conductive Biodegradable Scaffold with Coaxially Aligned Carbon Nanotubes for Directional Regeneration of Peripheral Nerves

Abstract

Fascicular rearrangement of an injured peripheral nerve requires reconnection of nerve sprouts from anterior and Büngner bands from distal sides of the lesion, failing to which leads to inefficient regeneration of the injured nerve. However, existing neural scaffolds have limited neuroregeneration efficiency because of either the lack of alignment of fibers and a conductive second phase, leading to compromised electrical conductivity, or the lack of extracellular matrix components and in vivo validation. The present study reports a biocompatible, multiwall carbon nanotube (MWCNT)-reinforced, anisotropically conductive, electrospun, aligned nanofibrous scaffold, ensuring maximal peripheral nerve regeneration. Electrospinning parameters were modulated to deposit random and parallel fibers in separate scaffolds for comparative analysis on the effect of fiber alignment on regeneration. Both types of scaffolds were reinforced with MWCNTs to impart electrical conductivity. Nonreinforced scaffolds were nonconductive. In this comparative study, MWCNT-reinforced, aligned scaffolds showed better tensile property with increased conductivity along the direction of alignment, thereby ensuring an escalated neural-regeneration rate. Collectively, in vitro studies established the scaffolds to be highly biocompatible, promoting cell growth and proliferation. With 85% more anisotropic conductivity in the direction of the alignment and the degradation kinetics tuned to the regeneration regime, the MWCNT-reinforced, aligned scaffold efficiently healed injured sciatic nerves in rats within 30 days. Rigorous revivification of the tissue was due to coordinated Wallerian degeneration and expedited guided axonal regeneration. Structural and functional analysis of nerves in vivo showed the aligned, MWCNT-reinforced scaffold to be very efficient in peripheral sciatic nerve regeneration. This study notes the efficacy of the coaxially aligned, MWCNT-reinforced neural scaffold, with a capability of establishing remarkable advancement in the field of peripheral neural regeneration.

Analysis of neural cell behaviour on anisotropic electrically conductive polymeric biodegradable scaffolds reinforced with carbon nanotubes

“…The alignment was achieved effectively only up to 5 wt% of MWCNTs, beyond which they started to agglomerate leading to a rough surface (Sung et al, 2004). Electrospinning could be a good technique to align the CNTs (Namgung et al, 2011) (Ghosh et al, 2020). But through spinning, CNT may align in radial direction instead of linear direction which is not at all required in peripheral neural tissue engineering.…”

“…Injuries of peripheral nerve were classified into neuropraxia, axonotmesis and neurotmesis bySeddon, (1943). Most of the time, PNI can result from acute trauma (road traffic incidents, construction accidents, gunshot wounds), laceration (a cut or tear in the nerve tissue), traction (stretching), compression, severe bruising (contusion), drug injection injury and electrical injury leading to paresthesia (abnormal sensation like tingling), dysesthesia (an unpleasant sensation), hypesthesia (low sensitivity to stimulus), loss of proprioception, numbness, motion abnormality, and even muscle atrophy and dysfunction(Ghosh et al, 2020; Henry, 2014; Menorca et al, 2013; Yi et al, 2019). Sadly, the regeneration or replacement capacity of neuronal tissue is very restricted in adults (Steward et al, 2012).…”

Biomedical Applications of Carbon Nanomaterials: Fullerenes, Quantum Dots, Nanotubes, Nanofibers, and Graphene

“…Ongoing research aims to provide a means for repair or even circumvention of this damage. Work conducted by Ghosh et al shows that electrospun nanofiber scaffolds containing MWCNTs demonstrated excellent regeneration properties for peripheral nerve cells in rats [109]. The nerve cells regenerated directionally, an important characteristic for functional nerve regeneration.…”

Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

“…On the other hand, we can explore the combination of anisotropic topographical cues and other biophysical and biochemical cues, like electrical stimuli and bioactive molecules. Some relevant studies have demonstrated promising results regarding in vitro neuron oriented growth and in vivo nerve regeneration [ 160 , [233] , [234] , [235] , [236] ]. To make them transplantable from bench to bedside, a stable power supply and sustained local therapeutic agent release still require optimization.…”