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

Lan Huong Nguyen,Jun Wang,Wutian Wu,Junquan Lin,Mingyong Gao,Sing Yian Chew

doi:10.1038/srep42212

Abstract

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. A hemi-incision model at cervical level 5 in the rat spinal cord was chosen to evaluate the efficacy of this scaffold design. Specifically, aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered. Taken together, our results demonstrate the potential of our scaffold for neural tissue engineering applications.

Highlights

Spinal cord injuries (SCI) irreversibly disrupt the spinal tracts and lead to permanent functional impairment
In this study, we incorporated NT-3 and miR-222 into the PCLEEP-collagen hybrid scaffold to evaluate the feasibility of a single scaffold in imparting synergistic biochemical and topographical signals to enhance nerve regeneration after SCI
Nerve regeneration may be further assisted by the synergistic supplementation of biomoleucles such as neurotrophic factors (e.g. NT-3) and microRNAs

Summary

Introduction

Spinal cord injuries (SCI) irreversibly disrupt the spinal tracts and lead to permanent functional impairment. The direct administration of biological factors to injury sites is frequently applied, such an approach often does not lead to robust tissue regeneration and reformation due to the rapid biological clearance of these agents from our bodies[1,2,3,4] Given this limitation, biodegradable scaffolds are increasingly employed as temporary frameworks for sustained delivery of biomolecules and to support neo-tissue formation. To mimic the mechanical properties of the spinal cord, hydrogels and self-assembled peptide nanofibers are commonly used[5,6,7,8,9,10] These scaffolds are often isotropic in architecture and lack the ability to direct the growth of regenerated axons through the extensively disorganized injured tissues for proper neuronal reconnections. We introduce a biodegradable, three-dimensional aligned nanofibers-hydrogel scaffold as a biofunctionalized platform to provide contact guidance and sustained non-viral drug/gene delivery for nerve injury treatment. The results showed that our biofunctionalized scaffolding platform effectively provided bio-mimicking contact guidance, and allowed the controlled delivery of various drugs and therapeutic biomolecules of drastically different nature and molecular weights

Methods

Results

Conclusion