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  4. Subcutaneous priming of protein-functionalized chitosan scaffolds improves function following spinal cord injury

Subcutaneous priming of protein-functionalized chitosan scaffolds improves function following spinal cord injury

Mater Sci Eng C Mater Biol Appl, 2020 · DOI: 10.1016/j.msec.2020.110656 · Published: May 1, 2020

NeurologyBiomedical

Simple Explanation

This study explores a novel approach to improve spinal cord injury (SCI) recovery by combining tissue engineering and regenerative medicine techniques. The approach involves using neural stem cell (NSC)-seeded scaffolds made of methacrylamide chitosan (MAC) with covalently immobilized interferon-γ (IFN-γ). The scaffolds are first matured in the subcutaneous environment of rats for 4 weeks to prime them for regeneration before being transplanted into the injured spinal cord. This subcutaneous priming aims to improve the integration and functional outcomes of the scaffolds. The study also investigates the effect of administering intracellular σ peptide (ISP), which reduces inhibition from the glial scar, in combination with the subcutaneously matured scaffolds to enhance locomotor function recovery after SCI.

Study Duration
16 Weeks
Participants
Female Fisher 344 rats
Evidence Level
Not specified

Key Findings

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    Subcutaneous maturation of NSC-seeded scaffolds combined with ISP administration improved locomotor function, as assessed by BBB scores and quantitative gait parameters, compared to a no treatment control.
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    Subcutaneous maturation decreased the neuronal differentiation of implanted cells, as indicated by decreased NeuN expression, and increased the expression of the neural precursor marker nestin in the implanted cells.
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    Robust neurofilament expression was observed at the periphery of the scaffold, and this was augmented by subcutaneous maturation and ISP administration, suggesting improved integration of the scaffold with the host tissue.

Research Summary

The study evaluated the effectiveness of subcutaneously maturing NSC-seeded scaffolds, formed from MAC and containing immobilized IFN-γ, in improving locomotor function following spinal cord injury in rats. The results showed that combining subcutaneous maturation with the administration of ISP, which reduces glial inhibition, led to improved recovery, as indicated by various functional tests and tissue-level examination. The findings suggest that the observed recovery was likely achieved through indirect trophic support from NSCs, with subcutaneous maturation enhancing this effect by maintaining the NSCs in an undifferentiated state and ISP facilitating host axon regrowth across the lesion.

Practical Implications

Therapeutic Strategy

Subcutaneous maturation of NSC-seeded scaffolds combined with ISP administration can be explored as a potential therapeutic strategy for improving locomotor function after spinal cord injury.

Trophic Support Mechanism

Indirect trophic support from NSCs plays a crucial role in promoting recovery, and strategies to enhance this effect, such as subcutaneous maturation, can be further investigated.

Combinatorial Approach

Combining multiple treatments, such as subcutaneous maturation, ISP administration, and potentially locomotor training, may be more effective than a single therapy in revolutionizing clinical SCI treatment.

Study Limitations

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