Three-dimensional aligned nanofibers-hydrogel scaffold for controlled non-viral drug/gene delivery to direct axon regeneration in spinal cord injury treatment

Scientific Reports, 2017 · DOI: 10.1038/srep42212 · Published: February 7, 2017

Spinal Cord Injury Pharmacology Biomedical

Simple Explanation

Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment. Aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered.

Study Duration

Not specified

Participants

Adult female Sprague Dawley rats (6–8 weeks, 200–250 g)

Evidence Level

Not specified

Key Findings

1
Aligned axon regeneration was observed as early as one week post-injury, indicating the contact guidance role of the scaffold.
2
The PCLEEP-collagen hybrid scaffold facilitated axonal remyelination in vivo, with MAG+ structures observed throughout the scaffolds at 4 weeks post-implantation, co-localized with NF+ axons.
3
Scaffold-mediated miR-222 delivery supported in vivo axon regeneration, with robust neurite ingrowth observed in PCLEEP-collagen hybrid scaffolds that incorporated miR-222 after 10 days post-implantation.

Research Summary

This study introduces an aligned nanofibers-hydrogel scaffold as a promising bio-functional platform for nerve injury treatment, providing localized and sustained release of drugs and nucleic acid molecules for non-viral transfection to enhance axon regeneration and remyelination in vivo. The aligned nanofibers provided topographical signals that effectively directed neurite extensions and supported remyelination within the lesion sites, demonstrating good host-implant integration. The application of these scaffolds may be translated to the clinical setting without raising biosafety concerns associated with viral-mediated methods, given the use of non-viral drug/gene delivery.

Practical Implications

Clinical Translation Potential

The non-viral drug/gene delivery approach minimizes biosafety concerns, facilitating potential clinical translation for SCI treatment.

Targeted Drug Delivery

The scaffold design allows for localized and sustained drug release, maximizing therapeutic effects at the injury site while minimizing systemic side effects.

Enhanced Axon Regeneration

The aligned nanofibers provide contact guidance, promoting directed neurite extension and improved axonal regeneration, leading to better functional outcomes.

Study Limitations

1
Behavior recovery was not assessed.
2
The 1/3 incision SCI model would not be sufficiently severe to result in significant differences in rat locomotion
3
Spontaneous recovery process following incomplete SCIs

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