Thermosensitive hydrogel-based GPR124 delivery strategy for rebuilding blood-spinal cord barrier

Bioeng Transl Med, 2023 · DOI: 10.1002/btm2.10561 · Published: May 25, 2023

Spinal Cord Injury Pharmacology Biomedical

Simple Explanation

Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), leading to further damage. This study explores a method to rebuild the BSCB using a thermosensitive hydrogel to deliver GPR124. The researchers found that GPR124 expression decreases after SCI. Treatment with recombinant GPR124 can partially restore the BSCB by improving tight junctions in endothelial cells and boosting their migration and tube formation. To improve GPR124's stability and delivery, a thermosensitive heparin-poloxamer (HP) hydrogel was created (HP@124). This hydrogel releases GPR124 slowly, protects wounded tissues, and fills injured cavities, promoting tissue repair and functional motor recovery post-SCI.

Study Duration

28 days

Participants

108 mature female SD rats

Evidence Level

Not specified

Key Findings

1
GPR124 expression decreases post-SCI, and recombinant GPR124 can partially alleviate BSCB disruption by restoring tight junctions and promoting endothelial cell migration and tube formation.
2
GPR124 boosts the energy metabolism of endothelial cells, suggesting a mechanism for its therapeutic effect.
3
HP@124 hydrogel induces synergistically efficient integrated regulation by blocking BSCB rupture, decreasing fibrotic scar formation, minimizing inflammatory response, boosting remyelination, and regenerating axons.

Research Summary

This research introduces a thermosensitive hydrogel-based GPR124 delivery strategy for early intervention in SCI, demonstrating notable physicochemical effects that inhibit BSCB disruption and promote motor function post-SCI. The HP@124 hydrogel is thermosensitive, protects GPR124 from degradation, and releases it sustainably, making it suitable for spinal cord applications. In vivo experiments showed that HP@124 hydrogel attenuated blood-spinal cord barrier permeability and protected blood-spinal cord barrier integrity by preventing the loss of tight junction proteins post-SCI, ultimately leading to ameliorated pathology and motor function.

Practical Implications

Therapeutic Potential

Early intervention combining GPR124 with bioactive multifunctional hydrogel shows promise for restoring locomotor recovery in central nervous system disorders and provides a translational approach for SCI medical therapy.

Drug Delivery Systems

The HP@124 hydrogel system can be applied to deliver other therapeutic proteins for SCI treatment.

Clinical Translation

The use of FDA-approved poloxamer in the hydrogel provides a promising potential for clinical translation of the therapeutic strategy.

Study Limitations

1
The dosage of GPR124 used in vivo requires further exploration.
2
There are still differences between rodents and humans in spinal cord size, anatomical structure, function, and inflammatory response.
3
The dura of rat is thin and easily disrupted by compression, resulting in the direct in situ injection of HP@124 hydrogel which is different from clinical cases.

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