Engineering functional vasculatures to reconstruct sympathetic-parasympathetic circuits for bladder function after...

Area of Science:

• Biomedical Engineering
• Neuroscience
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) causes neurogenic bladder dysfunction due to impaired nerve regeneration.
• Functional microvasculature is crucial for neural repair but is absent in injured spinal tissue.

Purpose of the Study:

• To engineer a hydrogel-based spinal cord substitute supporting vascularization and autonomic nerve regeneration.
• To restore bladder function following SCI through enhanced vascularization and neural repair.

Main Methods:

• Developed an integrating hydrogel spinal cord substitute with temporally staged angiogenic factors (VEGF, PDGFbb) and immune modulation.
• Delivered vascular endothelial growth factor (VEGF) for endothelial activation and platelet-derived growth factor-bb (PDGFbb) for vessel maturation.
• Utilized sustained immune modulation to stabilize newly formed vasculature.

Main Results:

• The spinal cord substitute successfully formed mature, perfused microvascular networks in vivo.
• Vascularization improved tissue metabolic capacity and supported autonomic axonal regeneration, myelination, and synaptic organization.
• Significant recovery of bladder function was observed after SCI.

Conclusions:

• Engineering functional vasculature within a spinal cord substitute is key for tissue integration and autonomic recovery.
• Vascular reconstruction is a critical foundation for restoring complex neural functions after SCI.
• This approach offers a promising strategy for treating neurogenic bladder dysfunction post-SCI.