Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

TISSUE ENGINEERING: Part A, 2016 · DOI: 10.1089/ten.tea.2015.0422 · Published: January 28, 2016

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This study investigates the potential of using injectable hydrogels made from extracellular matrix (ECM) to repair spinal cord injuries. The hydrogels, derived from porcine spinal cord (SC-ECM) and urinary bladder (UB-ECM), were injected into rats with spinal cord injuries to see if they could promote tissue regeneration. The researchers looked at how well the hydrogels integrated into the injured spinal cord, whether they stimulated the growth of new blood vessels and nerve fibers, and how the body's immune system responded to the hydrogels. They also tested whether combining the hydrogels with stem cells would improve the results. The results showed that both types of hydrogels could bridge the injury site and encourage the growth of new blood vessels and nerve fibers. However, the hydrogels degraded quickly, leading to cyst formation, and adding stem cells did not significantly improve the regeneration process.

Study Duration

8 Weeks

Participants

Male Wistar rats (250–300 g)

Evidence Level

Not specified

Key Findings

1
Both SC-ECM and UB-ECM hydrogels integrated into the SCI lesion site, stimulated neovascularization, and promoted axonal ingrowth into the lesion area.
2
Rapid degradation of the hydrogels and massive macrophage infiltration into the lesion did not prevent cyst formation, which progressed over the 8-week study period.
3
Gene expression analysis revealed a significant downregulation of genes related to the immune response and inflammation in both hydrogel types at 2 weeks post-SCI.

Research Summary

The study evaluated the neuroregenerative potential of injectable ECM hydrogels derived from porcine spinal cord (SC-ECM) and urinary bladder (UB-ECM) in an acute spinal cord injury (SCI) model in rats. Both hydrogel types integrated into the lesion, stimulated neovascularization and axonal ingrowth, and modulated the innate immune response. However, rapid hydrogel degradation and cyst formation were observed. Combining SC-ECM with human mesenchymal stem cells did not further promote axonal and blood vessel ingrowth compared to SC-ECM alone, suggesting the need for optimization of hydrogel degradation time and further analysis of neuronal function restoration.

Practical Implications

Biomaterial Design

The study highlights the need to optimize the degradation rate of ECM hydrogels to ensure sustained support for tissue regeneration in SCI.

Cell Therapy Strategies

Combining ECM hydrogels with stem cells may require further optimization to enhance cell survival and integration within the lesion site.

Immunomodulation

ECM hydrogels can modulate the innate immune response, suggesting potential for targeted immunomodulatory therapies in SCI.

Study Limitations

1
Fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.
2
Hemisection is a case of partial lesion with a high rate of spontaneous recovery and a high risk of inconsistencies in the injuries from one animal to the next, which might lead to misinterpretation of the behavioral evaluation.
3
The inﬂammatory milieu of the acute lesion together with the massive inﬁltration of macrophages did not support cell survival.

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