Thermo‑sensitive electroactive hydrogel combined with electrical stimulation for repair of spinal cord injury

J Nanobiotechnol, 2021 · DOI: https://doi.org/10.1186/s12951-021-01031-y · Published: September 8, 2021

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

Spinal cord injury (SCI) disrupts the connection between the brain and peripheral organs, leading to sensory motor dysfunction. In addition, SCI can lead to a series of secondary diseases, for example, deep vein thrombosis, muscle spasms, osteoporosis, urinary tract infections, bedsores, chronic pain, and respiratory complications, which are detrimental to the patient’s daily activities and even life-threatening. Electrical stimulation (ES) is commonly used for the treatment of SCI; in addition to maintaining muscle strength and volume and preventing denervated muscle atrophy, ES regulates the physiologic activities of nerve cells such as proliferation, differentia-tion, and axon growth. Herein, we prepared an electroactive hydrogel based on poly(amino acid) and the electrically responsive PANI, and combined this with ES to achieve a more potent therapeutic effect in the repair of SC tissue.

Study Duration

12 weeks

Participants

Wistar and Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
The developed hydrogel exhibits outstanding electrical conductance upon ES, with continuous release of NGF for at least 24 days.
2
In cultured nerve cells, TPEH loaded with NGF promoted the neuronal differentiation of neural stem cells and axonal growth, an effect that was potentiated by ES.
3
In a rat model of SCI, TPEH combined with NGF and ES stimulated endogenous neurogenesis and improved motor function.

Research Summary

The strategy of using a combination of scaffold-based physical and biochemical cues to repair spinal cord injury (SCI) has shown promising results. In summary, we prepared an electroactive hydro-gel scaffold by grafting conductive TA onto poly(l-valine). The hydrogel was porous and showed good biocompatibility, biodegradability, and conductivity, and effectively stimulated SC tissue repair through continuous slow release of NGF and in response to external ES. These features induced the differentiation of NSCs into neurons in the injured SC while inhibiting the proliferation of astrocytes. Implantation of the hydrogel in SCI model rats stimulated endogenous neurogenesis and promoted the restoration of motor function.

Practical Implications

Clinical Potential

The electroactive hydrogel loaded with NGF and combined with ES has clinical potential for the treatment of SCI.

Drug Delivery

The hydrogel can efficiently release NGF over a sufficiently long period of time to allow nerve cell growth after SCI.

Prevention of Glial Scarring

The hydrogel inhibits astrocyte proliferation and may prevent the formation of glial scars.

Study Limitations

1
The degree of gait recovery was different, which could be due to the different degrees of regeneration and conduction of nerve cells in the gray and white matter, respectively
2
inconsistent muscle tension caused by atrophic lower limb muscles may account for the observed differences
3
Not specified

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