Decellularized Biohybrid Nerve Promotes Motor Axon Projections

Advanced Healthcare Materials, 2024 · DOI: 10.1002/adhm.202401875 · Published: September 1, 2024

Biomedical Regenerative Medicine & Stem Cells

Simple Explanation

The study develops biohybrid nerves using decellularized rat sciatic nerve modified with a conductive polymer, PEDOT, to promote directed axon growth. Various polymerization conditions were tested, and a 1:1 ratio of FeCl3 oxidant to EDOT monomer, cycled twice, showed superior conductivity and compatibility. The biohybrid nerve effectively promotes directed motor axon growth, particularly when seeded with Schwann cells, suggesting a promising approach for axonal tract reconstruction.

Study Duration

14 days

Participants

Human Spinal Cord Spheroids (hSCS) derived from HUES 3 Hb9:GFP cells

Evidence Level

Not specified

Key Findings

1
A biohybrid nerve with a 1:1 ratio of FeCl3 to EDOT, cycled twice (DNP1:1C2), exhibited superior conductivity, mechanical alignment, and biocompatibility.
2
The biohybrid nerve (DNP1:1C2) significantly enhanced directed motor axon growth from human Spinal Cord Spheroids (hSCS).
3
Seeding the biohybrid nerve with Schwann cells (DNPsc1:1C2) further improved motor axon growth, indicating enhanced axonal tract reconstruction.

Research Summary

This study introduces a biohybrid nerve graft made of decellularized rat sciatic nerve and PEDOT, optimized for electrical conductivity, mechanical properties, and biocompatibility. The optimized biohybrid nerve (DNP1:1C2) enhances directed motor axon growth from human spinal cord spheroids, especially when seeded with Schwann cells. The biohybrid nerve closely meets all the criteria for an ideal conduit: preserved fascicular structures, conductivity of 0.214 mS cm-1, high compatibility with both cells and blood.

Practical Implications

Axonal Tract Reconstruction

The biohybrid nerve shows potential for reconstructing axonal tracts in severed nerve injuries, benefiting ≈200000 Americans with peripheral nerve damage.

Enhanced Nerve Repair

The combination of decellularized nerve and PEDOT improves electrical properties and biocompatibility, leading to better nerve regeneration.

Clinical Translation

The use of human spinal cord spheroids provides a translational model for assessing nerve repair strategies, offering advantages over animal models.

Study Limitations

1
The study is primarily in vitro, requiring in vivo validation to confirm its efficacy in animal models.
2
Long-term effects and potential degradation of PEDOT in the biohybrid nerve need further investigation.
3
The mechanical mismatch should closely resemble those found in natural nerves, providing an optimal guidance channel for axons and other cells to traverse.

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