Engineered nerve guide conduit enhances peripheral nerve regeneration by modulating the microenvironment through...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Immunomodulation

Background:

• Peripheral nerve injury (PNI) impairs nerve regeneration due to microenvironmental factors.
• Immune homeostasis and microenvironment remodeling are critical for successful nerve repair.
• Current strategies often lack sustained immunomodulatory effects.

Purpose of the Study:

• To develop and evaluate a double-layer nerve guide conduit for enhanced peripheral nerve regeneration.
• To investigate the immunomodulatory effects of sustained IL-4 release on macrophages and downstream cellular responses.
• To assess the therapeutic potential of the conduit in a long-distance nerve defect model.

Main Methods:

• Fabrication of a double-layer conduit (PSM/Gel-SC(IL-4)) using PEGDA, SAMA, and IL-4-overexpressing Schwann cells in GelMA.
• In vitro assessment of IL-4 sustained release and its effect on macrophage polarization via the JAK1/STAT6 pathway.
• In vivo evaluation in a 12-mm rat sciatic nerve defect model, assessing functional recovery, macrophage polarization, angiogenesis, and myelination.

Main Results:

• The PSM/Gel-SC(IL-4) conduit demonstrated sustained IL-4 release in vitro, inducing pro-healing macrophage polarization.
• In vivo, the conduit significantly promoted functional recovery and nerve regeneration in a rat sciatic nerve defect model.
• The conduit accelerated angiogenesis and myelination, while inducing pro-healing macrophage polarization at early stages.

Conclusions:

• The developed nerve guide conduit offers a novel immunomodulatory strategy for nerve regeneration.
• Sustained IL-4 release effectively reprograms the microenvironment, promoting macrophage polarization and subsequent cellular healing.
• This approach shows significant therapeutic potential for treating long-distance peripheral nerve defects.