Controlled Release of 6-Aminonicotinamide from Aligned, Electrospun Fibers Alters Astrocyte Metabolism and Dorsal Root Ganglia Neurite Outgrowth

J Neural Eng, 2011 · DOI: 10.1088/1741-2560/8/4/046026 · Published: August 1, 2011

Simple Explanation

Following central nervous system (CNS) injury, activated astrocytes form a glial scar that inhibits the migration of axons ultimately leading to regeneration failure. Electrospun fibers are a promising type of biomaterial for CNS injury since these fibers can direct cellular and axonal migration while slowly delivering therapeutic to the injury site. In this study, it was hypothesized that inclusion of an anti-metabolite, 6-aminonicotinamide (6AN), within poly-L-lactic acid (PLLA) electrospun fibers could attenuate astrocyte metabolic activity while still directing axonal outgrowth.

Study Duration

2 Weeks

Participants

E9 chick DRG and E10 chick spinal cord

Evidence Level

Not specified

Key Findings

1
6AN release from the fiber substrates occurred continuously over two weeks.
2
Astrocytes placed onto drug-releasing fibers were less active than those cultured on scaffolds without 6AN.
3
Dorsal root ganglia (DRG) placed onto control and drug-releasing scaffolds were able to direct neurites along the aligned fibers. However, neurite outgrowth was stunted by fibers that contained 20% 6AN.

Research Summary

This study investigated the possibility of using aligned, electrospun fibers loaded with a metabolic inhibitor (6AN) to selectively target astrocytes while allowing nerve growth. While it was difficult to design aligned fibers that release 6AN with characteristics shown to be conducive to nerve growth, proper parameters were determined to electrospin fibers that allowed similar growth to that of highly aligned scaffolds. These novel fiber scaffolds showed a high degree of control in releasing 6AN and at levels sufficient to significantly reduce astrocyte activity while in some cases, did not affect axonal extension from DRG neurons.

Practical Implications

Controlled Drug Release

Electrospun fibers can be used for controlled release of therapeutics to modulate cell behavior.

Targeted Astrocyte Modulation

6AN-releasing fibers can selectively target astrocytes to reduce their activity while preserving axonal growth.

CNS Injury Repair

Aligned, electrospun fibers loaded with 6AN may offer a potential strategy for promoting nerve regeneration after CNS injury.

Study Limitations

1
The study is limited by the in vitro nature of the experiments.
2
The DRG selection process may introduce bias in the results.
3
The study does not address the potential effects of 6AN on other cell types in the CNS.

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