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  4. An injectable heparin-Laponite hydrogel bridge FGF4 for spinal cord injury by stabilizing microtubule and improving mitochondrial function

An injectable heparin-Laponite hydrogel bridge FGF4 for spinal cord injury by stabilizing microtubule and improving mitochondrial function

Theranostics, 2019 · DOI: 10.7150/thno.37601 · Published: September 21, 2019

Regenerative MedicineNeurologyBiomedical

Simple Explanation

Spinal cord injury (SCI) is a serious condition that can cause loss of movement and feeling. The researchers developed a new way to deliver a protective protein called FGF4 directly to the injured spinal cord using a special gel made from heparin and Laponite. This gel helps to release the protein slowly and steadily over time. The gel, called Lap/Hep@FGF4, was tested in rats with SCI. The results showed that the rats treated with the gel had better motor function recovery and improved nerve regeneration. The gel also helped to reduce inflammation and scarring in the injured area. The researchers found that the Lap/Hep@FGF4 gel works by stabilizing microtubules, which are important structures in nerve cells, and by improving the function of mitochondria, which provide energy to the cells. This helps the nerve cells to regrow and repair themselves after injury.

Study Duration
28 days
Participants
84 adult female SD rats
Evidence Level
Level 1: Experimental study in SCI rat model and in vitro primary neuron culture

Key Findings

  • 1
    The Lap/Hep@FGF4 group showed remarkable motor functional recovery and axonal regrowth after SCI through suppressing inflammatory reaction, increasing remyelination and reducing glial/fibrotic scars.
  • 2
    Axonal rehabilitation was demonstrated via enhancing microtubule stability and regulating mitochondrial localization after Lap/Hep@FGF4 treatment.
  • 3
    A sustained release behavior of FGF4 was observed in the 7.6+19 mg/mL (H/L, 2:5) hydrogel, which could achieve spatial as well as temporal control in the delivery of FGF4.

Research Summary

This study introduces a novel injectable hydrogel (Lap/Hep@FGF4) designed for sustained release of FGF4 at the site of spinal cord injury (SCI). The hydrogel is composed of heparin and Laponite, which together create a stable carrier for the neuroprotective factor FGF4. In vivo experiments using a rat SCI model demonstrated that Lap/Hep@FGF4 treatment led to remarkable motor functional recovery and axonal regrowth. The treatment also suppressed inflammatory reactions, increased remyelination, and reduced glial/fibrotic scars. The underlying mechanism of axonal rehabilitation involves enhancing microtubule stability and regulating mitochondrial localization, providing a synergistic and effective approach to enhance recovery after SCI.

Practical Implications

Clinical Translation Potential

The injectable hydrogel system offers a clinically feasible therapeutic approach for patients suffering from SCI due to its ease of preparation, quick gelation, good biocompatibility, and biodegradability.

Novel Therapeutic Target

The study highlights the importance of microtubule stabilization and mitochondrial function in axonal regeneration, suggesting new targets for SCI treatment.

Drug Delivery System

The Lap/Hep hydrogel represents a versatile platform for controlled delivery of growth factors and other therapeutic agents to promote tissue regeneration in various biomedical applications.

Study Limitations

  • 1
    The study was conducted on a rat model, and the results may not directly translate to humans.
  • 2
    Further research is needed to optimize the dosage and release kinetics of FGF4 from the hydrogel.
  • 3
    Long-term effects of the Lap/Hep@FGF4 hydrogel on spinal cord tissue and function were not fully evaluated.

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