Genetically Programmed Single-Component Protein Hydrogel for Spinal Cord Injury Repair

Advanced Science, 2025 · DOI: 10.1002/advs.202405054 · Published: January 10, 2025

Simple Explanation

Researchers created a hydrogel from a single protein, CsgA, and enhanced it with GHK, a peptide known for reducing inflammation and promoting nerve growth. The hydrogel forms by the physical entanglement of CsgA nanofibers. This new hydrogel can change the behavior of immune cells (microglia) to reduce inflammation, encourage nerve stem cells to become nerve cells, and prevent other cells from forming scar tissue. When tested in rats with spinal cord injuries, the hydrogel reduced inflammation and helped nerves regenerate, leading to improved movement. This suggests it could be a good option for tissue repair.

Study Duration

5 Weeks

Participants

Sprague-Dawley rats (n=6 per group)

Evidence Level

Not specified

Key Findings

1
CsgA-GHK hydrogel modulates microglial M2 polarization in vitro, indicating an anti-inflammatory effect.
2
The hydrogel promotes neuronal differentiation of neural stem cells (NSCs) and inhibits astrocyte differentiation in vitro.
3
In a rat model of spinal cord injury, the CsgA-GHK hydrogel alleviates inflammation, promotes neuronal regeneration, and leads to significant functional recovery.

Research Summary

This study introduces a single-component hydrogel based on the recombinant protein CsgA, enhanced with the GHK peptide, for spinal cord injury (SCI) repair. The hydrogel's formation relies on the physical entanglement of CsgA nanofibers, providing a self-supporting structure at low concentrations. In vitro experiments demonstrated that the CsgA-GHK hydrogel modulates microglial M2 polarization, promotes neuronal differentiation of neural stem cells, and inhibits astrocyte differentiation, showcasing its potential to improve the cellular environment after SCI. In vivo studies using a rat model with compression injury spinal cord cavity revealed that the CsgA-GHK hydrogel alleviates inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery.

Practical Implications

Modular Design Platform

The findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in various tissue repair applications.

Therapeutic Potential of GHK

The study unveils a new dimension to the potential of the GHK tripeptide by showcasing its efficacy in nerve injury repair.

Advancement in SCI Treatment

The work will raise the prospects of designing active protein-based soft materials for advancing SCI treatment and other biomedical interventions.

Study Limitations

1
The specific degradation products and their long-term effects were not examined.
2
The study focuses on a compression injury model; efficacy in other SCI models may vary.
3
Longer-term studies are needed to assess the durability of functional recovery.

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