A Bioinspired Force-Inducible Hydrogel Conduit for Peripheral Nerve Regeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Neuroscience

Background:

• Long-gap peripheral nerve injuries (PNI) impede axon regeneration due to growth cone failure to detect distal neurotrophic signals.
• Current nerve guide conduits (NGCs) often fail to bridge long gaps effectively, limiting functional recovery.
• Autografts are effective but have limitations, including donor site morbidity and limited availability.

Purpose of the Study:

• To develop a bioinspired, force-inducible multichannel nerve guide conduit (FI-MNGC) for long-gap PNI.
• To mimic vascular plant capillary architectures to enhance neurotrophic signaling and cell guidance.
• To evaluate the efficacy of FI-MNGC in promoting nerve regeneration and functional recovery in animal models.

Main Methods:

• Fabrication of a silk fibrin-based hydrogel FI-MNGC with gradient apertures.
• Mimicking capillary forces found in vascular plants to create self-generating capillary forces.
• In vivo testing in rat (16 mm) and rabbit (30 mm) sciatic nerve defect models.

Main Results:

• The FI-MNGC successfully promoted directed axon growth across long nerve gaps.
• Guided delivery of Schwann cells (SCs) to the distal nerve stumps was achieved without external stimuli.
• FI-MNGC demonstrated accelerated nerve regeneration, functional recovery, and repair speed comparable to autografts.

Conclusions:

• The bioinspired FI-MNGC effectively overcomes challenges in long-gap PNI regeneration.
• The multichannel design with gradient apertures enhances capillary forces for directed growth and cell migration.
• FI-MNGC presents a promising, potentially clinically applicable alternative to nerve autografts for PNI treatment.