Nano-fiber/net artificial bionic dura mater promotes neural stem cell differentiating by time sequence external-oral administration to repair spinal cord injury

Theranostics, 2025 · DOI: 10.7150/thno.102584 · Published: January 27, 2025

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This study introduces a new approach to treat spinal cord injuries (SCI) using a nano-fiber/net artificial bionic dura mater (NABDM). This material is designed to reduce inflammation and promote the differentiation of neural stem cells (NSCs), which are crucial for repairing damaged nerve tissue. The NABDM has a core-shell structure, with nafamostat mesylate (NM) in the outer layer to reduce inflammation and neurotrophin-3 (NT3) in the inner layer to promote NSC differentiation. The material is designed for sequential drug delivery. The NABDM aims to create an optimal environment for NSC differentiation and support nerve regeneration, offering a promising strategy for SCI treatment and potential clinical applications.

Study Duration

28 days

Participants

Female C57BL/6 mice aged 6–8 weeks

Evidence Level

Not specified

Key Findings

1
NABDM modifies the polarization direction of microglia in vitro, and promotes the differentiation of NSCs by activating the cGMP–PKG and cAMP signaling pathways.
2
In a mouse SCI model, NABDM effectively reduces local neuroinflammation, accelerates the differentiation of endogenous NSCs, increases the number of mature neurons, and enhances motor, sensory, and autonomic nerve functions in mice.
3
NABDM promotes the differentiation of NSCs and facilitates the repair of SCI in a time sequence external-oral way.

Research Summary

The study successfully synthesized NABDM using coaxial electrospinning technology, creating core-shell structured nano-fiber/nets. This structure ensures time-specific drug release and improves mechanical strength compared to single structures. NABDM reduces local neuroinflammation, accelerates endogenous NSC differentiation, and increases the number of mature neurons. This results in improved motor, sensory, and autonomic nerve functions in mice with SCI. The NABDM represents a new, rapid, and effective treatment for SCI, suitable for clinical use as a patch and particularly valuable for prehospital emergency treatment.

Practical Implications

Clinical Application

NABDM can be used as a patch for prehospital emergency treatment of acute SCI, offering a rapid and simple application method.

Drug Delivery System

The coaxial electrospinning technology allows for the creation of core-shell structures that ensure time-specific drug release, avoiding side effects from drug overdose.

Biomaterial Design

The study demonstrates the importance of considering mechanical properties in biomaterial design, as the NABDM has a mechanical strength comparable to that of the spinal cord dura mater.

Study Limitations

1
The study did not investigate downstream pathways, such as the Notch pathway, which is related to neural differentiation, or other pathways involving ERK.
2
The duration of mouse observation after SCI was relatively short, necessitating long-term studies to assess chronic SCI recovery.
3
The NABDM lacks the ability to treat both sides and the ventral side of the injured spinal cord and can perform only 2D-level treatment.

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