Electrospun Fibers for Drug Delivery after Spinal Cord Injury and the Effects of Drug Incorporation on Fiber Properties

Abstract

There is currently no cure for individuals with spinal cord injury (SCI). While many promising approaches are being tested in clinical trials, the complexity of SCI limits several of these approaches from aiding complete functional recovery. Several different categories of biomaterials are investigated for their ability to guide axonal regeneration, to deliver proteins or small molecules locally, or to improve the viability of transplanted stem cells. The purpose of this study is to provide a brief overview of SCI, present the different categories of biomaterial scaffolds that direct and guide axonal regeneration, and then focus specifically on electrospun fiber guidance scaffolds. Much like other polymer guidance approaches, electrospun fibers can retain and deliver therapeutic drugs. The experimental section presents new data showing the incorporation of two therapeutic drugs into electrospun poly-<smlcap>L</smlcap>-lactic acid fibers. Two different concentrations of either riluzole or neurotrophin-3 were loaded into the electrospun fibers to examine the effect of drug concentration on the physical characteristics of the fibers (fiber alignment and fiber diameter). Overall, the drugs were successfully incorporated into the fibers and the release was related to the loading concentration. The fiber diameter decreased with the inclusion of the drug, and the decreased diameter was correlated with a decrease in fiber alignment. Subsequently, the study includes considerations for successful incorporation of a therapeutic drug without changing the physical properties of the fibers.

Harnessing stem cells and biomaterials to promote neural repair

“…Aligned PLA fibres were emulsion electrospun with 6‐aminonicotinamide (6AN); the material demonstrated a 2 week sustained release and concomitantly reduced astrocyte activity (effect of 6AN) and directed dorsal root ganglia axonal outgrowth (effect of fibre alignment) (Schaub and Gilbert, ). A drawback of this technique is that emulsion electrospinning can affect the material properties of the fibre scaffold, including fibre diameter and alignment (Johnson et al, ).…”

Nanofiber Scaffolds as Drug Delivery Systems to Bridge Spinal Cord Injury

“…It is considered a global issue, affecting people of every age and concerning almost 2.5 million patients worldwide. Despite the fact that, in the last decades, improvements in medical care have increased patient survival rates and reduced the impact of SCI on life quality, a therapeutic approach for the regeneration of damaged cells and for the recovery of motor functions is still lacking [ 2 ]. Therefore, effective multifaceted therapies, aiming at reducing the extent of tissue disruption and improving neurologic outgrowth after spinal cord trauma, are urgently needed.…”

“…The pathophysiological response to a spinal cord injury involves a primary damage, followed by the activation of a cascade of secondary events. SCI instauration and progression are generally divided into acute (seconds to minutes after the traumatic event), intermediate (minutes to weeks after the trauma) and chronic (months to years) phases [ 2 , 3 ] ( Figure 1 ).…”

“…Axon distal segment, unconnected with the neuron soma, crushes and activates a process called Wallerian degeneration, which determines apoptosis of the oligodendrocytes surrounding distal segments [ 2 , 8 ]. The secondary damage ends with the formation of a glial scar, which can further impede axonal regeneration.…”

Removal of retained electrospinning solvent prolongs drug release from electrospun PLLA fibers

“…[12–16] For cellular applications, electrospinning creates polymer nanofibers with diameters similar to those of fibrous proteins found in the extracellular matrix. Due to the fibers resembling the structure of the extracellular matrix, aligned, electrospun fibers are used as tissue engineering scaffolds to guide directional tissue regeneration.…”