NT-3 functionalized multiscale bilayer scaffold for peripheral nerve regeneration with radial axonal branching

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Peripheral nerve injury (PNI) impairs motor and sensory functions.
• Current regenerative grafts primarily support axial nerve regrowth, neglecting collateral branching.
• Addressing both axial and radial axonal regeneration is crucial for full functional restoration.

Purpose of the Study:

• To develop a multiscale bilayer scaffold for bidirectional peripheral nerve regeneration.
• To functionalize the scaffold with a gradient of Neurotrophin-3 (NT-3) to promote radial axonal branching.
• To enhance functional recovery by restoring both motor and sensory functions.

Main Methods:

• Fabrication of a polycaprolactone-collagen peptide-based bilayer scaffold using electrospinning and 3D printing.
• Incorporation of a spatially controlled concentration gradient of NT-3 within the scaffold.
• In vitro evaluation of neuronal cell adhesion, migration, proliferation, and radial axonal branching using microscopy.
• In vivo assessment of scaffold efficacy on a crushed rat sciatic nerve model.

Main Results:

• The nanofibrous layer mimicked the extracellular matrix, promoting neuronal cell interactions.
• In vitro studies confirmed NT-3's role in inducing radial axonal branching.
• In vivo functional and behavioral tests demonstrated that NT-3 scaffolds enhance bidirectional nerve regeneration.
• Evidence of potential for radial axonal branching was observed in vivo.

Conclusions:

• The developed bilayer scaffold effectively promotes bidirectional peripheral nerve regeneration.
• NT-3 functionalization is key to achieving radial axonal branching for improved functional recovery.
• This approach holds promise for treating peripheral nerve injuries by restoring both motor and sensory functions.