Electrospun Fibers for Spinal Cord Injury Research and Regeneration

Abstract

Electrospinning is the process by which a scaffold containing micrometer and nanometer diameter fibers are drawn from a polymer solution or melt using a large voltage gradient between a polymer emitting source and a grounded collector. Ramakrishna and colleagues first investigated electrospun fibers for neural applications in 2004. After this initial study, electrospun fibers are increasingly investigated for neural tissue engineering applications. Electrospun fibers robustly support axonal regeneration within in vivo rodent models of spinal cord injury. These findings suggest the possibility of their eventual use within patients. Indeed, both spinal cord and peripheral nervous system regeneration research over the last several years shows that physical guidance cues induce recovery of limb, respiration, or bladder control in rodent models. Electrospun fibers may be an alternative to the peripheral nerve graft (PNG), because PNG autografts injure the patient and are limited in supply, and allografts risk host rejection. In addition, electrospun fibers can be engineered easily to confront new therapeutic challenges. Fibers can be modified to release therapies locally or can be physically modified to direct neural stem cell differentiation. This review summarizes the major findings and trends in the last decade of research, with a particular focus on spinal cord injury. This review also demonstrates how electrospun fibers can be used to study the central nervous system in vitro.

Keywords: axonal regeneration; in vitro studies; in vivo studies; spinal cord injury.

FIG. 1.

The panel A–F provides a schematic representation of conduit fabrication. PLLA fibers are electrospun onto coverslips coated with PLLA films on a rotating mandrel (A,B). The film and fibers are removed from the coverslip (C) and placed back-to-back, so the films meet, and are rolled into a conduit (D,E). The final conduit shape is shown as a schematic (F) and the lumen (M) and coronal view (N) are shown under Scanning electron microscopy (SEM.) Random fibers were produced by electrospinning onto a stationary target (G) while aligned fibers were produced using the rotating mandrel (I). Aligned fibers in the conduit maintained their alignment through the processing in steps C–E (K,L). The alignment for each group was determined by SEM imaging. Alignment was reported as a histogram of the angle differences from the median fiber orientation for 150 fibers per condition (H,J,L). Scale Bars: (G) 50 μm; (I, K) 100 μm; (M,N) 1 mm. This figure was reproduced from Hurtado and associates.

FIG. 2.

An illustration of how fiber geometry affects neurite extension from dorsal root ganglia (DRG) on electrospun fibers. The blue/green objects in the illustrations on the right side of the figure indicate the DRG body. When electrospun fibers are aligned and the fiber diameter is above 750 nm, neurites extend along the fibers (A). When electrospun fibers are aligned but the fiber diameter is below 750 nm, neurites will still follow the fibers, but the neurites tend to be shorter and appear to wander in less of a straight line along the fibers (B). When electrospun fibers are randomly aligned, neurites tend to grow in all directions (C). Color image is available online at www.liebertpub.com/neu