Tissue engineering approaches to modulate the inflammatory milieu following spinal cord injury

Cells Tissues Organs, 2016 · DOI: 10.1159/000446646 · Published: January 1, 2016

Spinal Cord Injury Immunology Biomedical

Simple Explanation

Tissue engineering shows promise for healing after spinal cord injury (SCI), but is limited by inflammation. Inflammation causes secondary damage, increased scarring, and an inhibitory environment for neuron regeneration. The immune response is crucial for closing the blood brain barrier, minimizing injury spread, and initiating healing. The review summarizes strategies to modulate the immune response towards an anti-inflammatory environment, permissive to regeneration. Emerging research strategies aim to enhance clinical treatments by directly targeting specific aspects of the immune response to enhance regeneration of neurons, glia and parenchyma.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Biomaterial scaffolds can provide physical guidance for regenerating axons and limit leukocyte infiltration, but their interactions with immune cells are complex and affected by physical and chemical properties.
2
Nanoparticles can be used to deliver therapeutics and modulate the immune cell response, with some particles selectively internalized by pro-inflammatory macrophages and microglia following SCI.
3
Gene therapy provides sustained expression of therapeutic molecules to modulate the immune response, with viral vectors offering greater transduction efficiency and expression levels.

Research Summary

Tissue engineering strategies for SCI are limited by inflammation, leading to secondary damage and inhibiting neuron regeneration. Modulating the immune response towards an anti-inflammatory environment is crucial for promoting regeneration. Biomaterials, biologically active molecules, gene therapy, nanoparticles, and stem cells are used to modulate the immune response. Strategies include scaffolds, particle delivery, and therapeutic molecule delivery. Future therapies should combine these approaches to directly promote regeneration while mitigating inflammation, without impairing wound healing and closing of the blood brain barrier.

Practical Implications

Design of Immunomodulatory Scaffolds

Consider pore size, geometry, and material properties to promote M2 macrophage polarization and reduce FBGC formation.

Targeted Nanoparticle Delivery

Use nanoparticles to selectively target pro-inflammatory immune cells and deliver therapeutics to modulate their phenotype.

Combination Therapies

Combine biomaterials, biologically active molecules, gene therapy, and cell transplants to synergistically promote regeneration and mitigate inflammation.

Study Limitations

1
Individual approaches to immunomodulation have limited capacity to directly promote regeneration.
2
Small improvements in rodent sensorimotor function do not always translate to clinically significant improvements in humans.
3
The mechanisms by which therapies modulate the immune system need further investigation to optimize efficacy.

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