Structure-Inspired Lineage-Specific Matrix for Endogenous Neurogenesis in Spinal Cord Injury

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) often results in permanent disability due to limited neuronal regeneration.
• Decellularized spinal cord (DSC) matrices offer a natural 3D structure but have poor mechanical properties and growth factor availability.
• Existing scaffolds struggle to provide adequate support for functional spinal cord repair.

Purpose of the Study:

• To develop an enhanced scaffold for spinal cord repair by combining DSC with a growth factor-eluting hydrogel.
• To investigate the potential of this engineered matrix to promote lineage-specific neuronal regeneration and functional recovery in vivo.
• To elucidate the underlying mechanisms of enhanced neurogenesis and reduced scarring.

Main Methods:

• Fabrication of a core-shell structure using 3D printing and electrostatic adsorption to reinforce DSC with a hydrogel matrix.
• Incorporation of neurogenic cues and growth factors into the engineered matrix.
• In vivo evaluation of the matrix's efficacy in promoting neuronal regeneration, reducing scar formation, and improving functional recovery after SCI.

Main Results:

• The engineered matrix significantly enhanced neuronal regeneration, with an 11-fold increase in newly generated neuronal cells.
• The scaffold promoted lineage-specific neuronal regeneration and activated the ITGA2/ITGA11-ERK/AKT signaling pathway.
• The matrix facilitated M2 macrophage/microglia polarization, reducing cavity and scar formation, and improving functional recovery.

Conclusions:

• The developed structure-inspired, lineage-specific matrix effectively stimulates endogenous neurogenesis and spinal cord repair.
• This approach offers a promising strategy for advancing therapeutic interventions for spinal cord injury.
• The combination of biomimetic structure and biochemical cues represents a significant step towards functional spinal cord regeneration.