Triple-Cue-Guided Multichannel Hydrogel Conduit to Synergistically Enhance Peripheral Nerve Repair

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Large nerve defects pose significant challenges for regeneration.
• Current nerve guidance conduits (NGCs) show promise but can be improved.
• Synergistic cues are needed to enhance nerve repair efficacy.

Purpose of the Study:

• To develop a novel multichannel NGC incorporating topographical guidance, conductivity gradient, and NGF gradient.
• To evaluate the efficacy of the NGC in promoting peripheral nerve regeneration both in vitro and in vivo.
• To assess the functional recovery and histological outcomes after nerve repair using the NGC.

Main Methods:

• Fabrication of an aligned hydrogel conduit via directional lyophilization of graphene oxide (GO)/poly(vinyl alcohol) (PVA).
• Creation of a conductivity gradient using dopamine-induced reduction of GO, simultaneously generating an amino group gradient.
• Formation of a nerve growth factor (NGF) gradient facilitated by the amino groups.
• In vitro testing on PC12 neuronal cells and in vivo testing in animal models.

Main Results:

• The NGF-gradient/aligned PVA/reduced graphene oxide (rGO)/polydopamine (PDA)/heparin hydrogel conduit (NGF-AGHC) demonstrated excellent guidance and neuritogenesis in vitro.
• In vivo studies showed NGF-AGHC enhanced axonal attraction and remyelination.
• Histological and functional assessments confirmed significant peripheral nerve regeneration, comparable to autografts.

Conclusions:

• The developed NGC effectively integrates topographical, conductivity, and NGF gradients for enhanced nerve regeneration.
• The straightforward preparation method offers a promising approach for peripheral nerve repair.
• NGF-AGHC shows potential as a viable alternative to autografts for treating large nerve defects.