Evaluation of Early and Late Effects into the Acute Spinal Cord Injury of an Injectable Functionalized Self-Assembling Scaffold

PLoS ONE, 2011 · DOI: 10.1371/journal.pone.0019782 · Published: May 18, 2011

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This study examines a new injectable material, a self-assembling peptide (SAP) scaffold, designed to help repair spinal cord injuries. The SAP is designed to mimic the structure of the support system around cells, called the extra-cellular matrix (ECM). The SAP used in this study, RADA16-4G-BMHP1, was injected into rats immediately after a spinal cord injury to see if it could help the tissue heal. Researchers watched the rats for eight weeks, checking how well they could move and examining the spinal cord tissue. The results showed that the SAP encouraged the growth of nerve tissue and improved motor function in the rats. This suggests the SAP could be a useful tool for treating spinal cord injuries in humans, possibly in combination with cells or growth factors.

Study Duration

8 weeks

Participants

45 female Sprague-Dawley rats

Evidence Level

Level 2: Animal Study

Key Findings

1
The functionalized SAP, RADA16-4G-BMHP1, induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins at 7 days after lesion.
2
Histological analysis revealed that 8 weeks after SCI the scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst.
3
SAP injection resulted in a statistically significant improvement of both hindlimbs’ motor performance and forelimbs-hindlimbs coordination.

Research Summary

This study evaluated the neurorigenerative properties of RADA16-4G-BMHP1 SAP by injecting the scaffold immediately after contusion in the rat spinal cord, then evaluating the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. SAP injection resulted in a statistically significant improvement of both hindlimbs’ motor performance and forelimbs-hindlimbs coordination, indicating that RADA16-4G-BMHP1 induced favourable reparative processes.

Practical Implications

Therapeutic Potential

The RADA16-4G-BMHP1 scaffold shows promise as a biomimetic scaffold for regenerative applications in the injured central nervous system.

Combination Therapies

The biomaterial could be combined with cells and growth factors to further enhance regenerative effects.

Matrix for In Vivo Delivery

RADA16-4G-BMHP1 could constitute a good matrix for the in vivo delivery of growth factors and/or NSCs into the injured CNS.

Study Limitations

1
The scaffold didn’t show a relevant neuroprotective effect, as we didn’t observe an attenuation of inflammatory processes nor a lesser extent of cyst and cavities in treated animals compared to untreated ones.
2
The injection procedure, even if less invasive than other implantation techniques, can have induced a tissue loss and cell death due to needle insertion and can be then resulted in a slight increment of the sub-acute inflammatory response.
3
The observed increment of mRNA expression of pro-inflammatory and pro-astrogliosis genes at 7 dpi didn’t lead to relevant anatomopatological changes at 8 weeks after SCI.

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