Abstract

Central and peripheral neural injuries are traumatic and can lead to loss of motor and sensory function, chronic pain, and permanent disability. Strategies that bridge the site of injury and allow axonal regeneration promise to have a large impact on restoring quality of life for these patients. Engineered materials can be used to guide axonal growth. Specifically, nanofiber structures can mimic the natural extracellular matrix, and aligned nanofibers have been shown to direct neurite outgrowth and support axon regeneration. In addition, cell-seeded scaffolds can assist in the remyelination of the regenerating axons. The electrospinning process allows control over fiber diameter, alignment, porosity, and morphology. Biodegradable polymers have been electrospun and their use in tissue engineering has been demonstrated. This paper discusses aspects of electrospun biodegradable nanofibers for neural regeneration, how fiber alignment affects cell alignment, and how cell-seeded scaffolds can increase the effectiveness of such implants.

Highlights

  • The nervous system comprises the peripheral nervous system (PNS) and the central nervous system (CNS)

  • This review summarizes the development of the electrospinning technique and methods to produce aligned nanofibers for neural regeneration applications (Section 2)

  • By tilting the knife-edged aluminum bar through a certain angle, Teo et al demonstrated the production of diagonally aligned fibers, as well as a multi-layered patterned tubular laminate composite of fibers in different diagonal directions [101]. Another technique of using auxiliary electrodes to facilitate the formation of aligned fibers was proposed by Lee et al, in which two auxiliary electrodes were introduced: one was a cylindrical electrode attached to the nozzle to stabilize the ejected polymer solution; and the other was a field-controllable electrode producing an alternating current electric field attached to the rotating collector [102]

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Summary

Introduction

The nervous system comprises the peripheral nervous system (PNS) and the central nervous system (CNS). When designing guidance channels made from either hydrogel [18,22,23] or polymer fibers, the following factors require consideration: they should be biodegradable, biocompatible, and permissive for cell growth; include neurostimulatory extracellular matrix (ECM) macromolecules (such as laminin-1 or laminin-1 fragments); include supportive cells, such as Schwann cells and stem cells; and include neurotrophic factors, such as neural growth factor (NGF—See Table 1 for abbreviations of materials in this paper) and brain-derived neurotrophic factor (BDNF) [24,25,26,27,28,29,30,31,32,33,34]. We survey the improved in vitro cell guidance that is achieved using aligned nanofiber scaffolds compared to random nanofiber mats, and examine the efficacy of cell seeding and/or neurotrophic factor incorporation into implantable structures in enhancing in vitro and in vivo regeneration (Section 5)

Electrospun Nanofibers
Factors Affecting Nanofiber Morphology and Structure
Aligned Fibers
Rotating Mandrels
Parallel Bars
Other Strategies for Fiber Alignment
Biodegradable Polymers
Polysaccharide Nanofibers
Protein Nanofibers
Biodegradable Synthetic Polymer Nanofibers
Permissive Environment for Regeneration
Cell Transplantation and Cell-Seeded Constructs
Schwann Cells
Neural Stem Cells
Neural Progenitor Cells
Olfactory Ensheathing Cells
Neurotrophic Factors
Aligned Electrospun Polymer Fiber Scaffolds Guide Cells
Aligned Schwann Cells Direct Aligned Neurite Outgrowth
Findings
Conclusions
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