Aligned Protein–Polymer Composite Fibers Enhance Nerve Regeneration: A Potential Tissue‐Engineering Platform

Abstract

Sustained release of proteins from aligned polymeric fibers holds great potential in tissue-engineering applications. These protein-polymer composite fibers possess high surface-area-to-volume ratios for cell attachment, and can provide biochemical and topographic cues to enhance tissue regeneration. Aligned biodegradable polymeric fibers that encapsulate human glial cell-derived neurotrophic factor (GDNF, 0.13 wt%) were fabricated via electrospinning a copolymer of caprolactone and ethyl ethylene phosphate (PCLEEP) with GDNF. The protein was randomly dispersed throughout the polymer matrix in aggregate form, and released in a sustained manner for up to two months. The efficacy of these composite fibers was tested in a rat model for peripheral nerve-injury treatment. Rats were divided into four groups, receiving either empty PCLEEP tubes (control); tubes with plain PCLEEP electrospun fibers aligned longitudinally (EF-L) or circumferentially (EF-C); or tubes with aligned GDNF-PCLEEP fibers (EF-L-GDNF). After three months, bridging of a 15 mm critical defect gap by the regenerated nerve was observed in all the rats that received nerve conduits with electrospun fibers, as opposed to 50% in the control group. Electrophysiological recovery was seen in 20%, 33%, and 44% of the rats in the EF-C, EF-L, and EF-L-GDNF groups respectively, whilst none was observed in the controls. This study has demonstrated that, without further modification, plain electrospun fibers can help in peripheral nerve regeneration; however, the synergistic effect of an encapsulated growth factor facilitated a more significant recovery. This study also demonstrated the novel use of electrospinning to incorporate biochemical and topographical cues into a single implant for in vivo tissue-engineering applications.

The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation

“…Since it has been observed that few major quality differences exist in the molecular expression between Schwann cells in distal nerve stumps and Schwann cells cultured in vitro in the absence of neurons [44], cultured Schwann cells may serve as a model of denervated Schwann cells in the distal stump of an injured nerve. Although we do not know if the relative levels of neurotrophic expression by seeded Schwann cells versus endogenous Schwann cells are comparable; we believe that the possible enhancement in the maturation of Schwann cells in contact with electrospun fibers as compared to a flat surface may thus be one of the reasons for the enhanced sciatic nerve regeneration observed in our previous study [9].…”

“…The potential of electrospun fibrous scaffolds in enhancing nerve regeneration was demonstrated previously [9]. Electrospun fibers can encapsulate bioactive drugs and proteins [10][11][12] and may be used as tissue scaffolds for direct in vivo applications [9].…”

“…Electrospun fibers can encapsulate bioactive drugs and proteins [10][11][12] and may be used as tissue scaffolds for direct in vivo applications [9]. Inclusion of aligned electrospun fibers in a nerve conduit could enhance sciatic nerve regeneration over a 15 mm critical size defect in rats after 3 months post-implantation [8].…”

The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons

“…Aligned electrospun nanofibers powerfully direct the growth of regenerating neurites in vitro, offering promise as scaffolds for peripheral nerve repair [1][2][3][4]. Additionally, nanofiber scaffolds may be useful in guiding regenerating neurons in the spinal cord and brain, as well as serve to differentiate and guide transplanted neurons and stem cells in nervous system lesions.…”

Porous Polymeric Bioresorbable Scaffolds for Tissue Engineering

“…Organic solvent and water are subsequently removed by freeze drying leaving a solid porous polymer with porosity up to 90% [96]. This technique has been applied to many biocompatible polymers such as PLA, PGA, PLAGA, PCL, chitosan and alginate [97][98][99][100]. Despite its versatility, freeze drying is a time and energy consuming method that takes several days to completely eliminate solvents.…”