Neonatal Spinal-Cord-Like Scaffold with Hierarchical Structural and Neurogenetic Microenvironments for Spinal Cord...

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) presents significant repair challenges due to complex regeneration and limited self-healing.
• Biomimetic scaffolds offer a promising strategy for SCI repair by mimicking natural biological processes.
• Neonatal spinal cords exhibit efficient self-healing properties, providing inspiration for regenerative approaches.

Purpose of the Study:

• To develop a neonatal spinal-cord-like scaffold (NSLS) for stage-specific regulation of SCI repair.
• To investigate the biomimetic features and mechanical properties of the NSLS.
• To evaluate the efficacy of NSLS loaded with neural stem cells (NSLT) in promoting nerve regeneration and functional recovery.

Main Methods:

• Fabrication of NSLS using a neonatal spinal cord matrix, laser processing, and dual-network cross-linking.
• Characterization of NSLS microenvironments for activating neural stem cells (NSCs).
• In vivo evaluation of NSLT for hemostasis, host integration, inflammation modulation, and axonal regeneration.

Main Results:

• NSLS successfully mimicked neonatal spinal cord properties, activating NSC metabolism, synaptic formation, and gliogenesis.
• NSLS facilitated early-stage SCI repair through rapid hemostasis and host integration.
• NSLT promoted M2 microglial polarization, reduced inflammation, guided axonal growth, and enhanced functional recovery.

Conclusions:

• The developed NSLT represents a promising therapeutic strategy for enhancing nerve regeneration and functional recovery after SCI.
• Stage-specific regulation by NSLT addresses the complex challenges of SCI repair.
• This biomimetic approach holds potential for future clinical applications in treating spinal cord injuries.