Biomimetic 3D-printed scaffolds for spinal cord injury repair

Nat Med, 2019 · DOI: 10.1038/s41591-018-0296-z · Published: February 1, 2019

Regenerative Medicine Neurology Biomedical

Simple Explanation

This study introduces a novel method, microscale continuous projection printing (μCPP), to create 3D biomimetic hydrogel scaffolds for spinal cord injury (SCI) repair. These scaffolds are designed to mimic the complex structure of the spinal cord and promote axon regeneration. The 3D-printed scaffolds, when loaded with neural progenitor cells (NPCs), can support axon regeneration and the formation of new 'neural relays' across complete SCI sites in rodents. This approach offers a potential means for enhancing CNS regeneration through precision medicine. The scaffolds are designed to fit the precise anatomy of an individual's injury, stimulating, guiding, and aligning axon regeneration. The scaffolds also appear to protect grafted cells from inflammatory mediators and reactive oxygen species in acute SCI lesion sites.

Study Duration

5 Months

Participants

Fischer rats

Evidence Level

Not specified

Key Findings

1
Injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device.
2
Implanted NPCs extend axons out of the scaffold and into the host spinal cord below the injury, restoring synaptic transmission and significantly improving functional outcomes.
3
3D biomimetic scaffolds plus NPC grafts significantly enhance host axonal regeneration into, and occasionally beyond, the lesion.

Research Summary

This study demonstrates the use of rapid 3D printing to create biomimetic central nervous system structures that can be individualized and scaled to patient-specific lesion shapes and lengths. The scaffolds support engraftment of NPCs acutely after injury and promote linear growth of regenerating host and stem cell-derived axons as they traverse the scaffolds. PEGDA-GelMa scaffolds re-engineer the astrocyte response at the injury site, aligning host astrocytes with the growth axis of host axonal fascicles, supporting extensive host axonal regeneration.

Practical Implications

Personalized Medicine

The 3D printing technology allows for the creation of personalized scaffolds tailored to the specific anatomy of an individual's spinal cord injury, potentially improving treatment outcomes.

Early Intervention

The scaffold supports engraftment of NPCs acutely after injury, allowing for early intervention with neural stem cell grafts, which aligns with the timing of surgical decompression in many SCI patients.

Enhanced Axon Regeneration

The biomimetic design and material properties of the scaffold promote axon regeneration and the formation of new neural relays across the injury site, leading to improved functional outcomes.

Study Limitations

1
The study was conducted on rodents, and further research is needed to translate these findings to human clinical trials.
2
The long-term effects of scaffold degradation and biocompatibility need further investigation.
3
The specific mechanisms underlying the re-engineering of the astrocyte response by the scaffolds are not fully elucidated.

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