Combinatorial tissue engineering partially restores function after spinal cord injury.

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) results in limited regeneration and significant functional deficits.
• Hydrogel scaffolds offer a promising strategy to create a supportive microenvironment for SCI repair.
• Reducing the foreign body response to implanted biomaterials is crucial for successful regeneration.

Purpose of the Study:

• To investigate the efficacy of a combinatorial biomaterials strategy for promoting spinal cord regeneration.
• To evaluate the sustained release of rapamycin from poly lactic-co-glycolic acid microspheres embedded in hydrogel scaffolds.
• To assess the impact of Schwann cells and rapamycin on reducing fibrotic reactions and enhancing functional recovery post-SCI.

Main Methods:

• Fabrication of oligo-polyethylene glycol fumarate hydrogel scaffolds loaded with Schwann cells and rapamycin-releasing microspheres.
• In vitro assessment of rapamycin release kinetics and biological activity.
• In vivo implantation of scaffolds in transected rat spinal cords across different rapamycin dosages.
• Immunohistochemical, stereological, and functional analyses to evaluate regeneration and vascularization.

Main Results:

• A dose-dependent reduction in fibrotic scarring around the scaffold was observed with increasing rapamycin doses.
• Significant improvements in functional recovery were noted in rats treated with the combinatorial scaffold over 6 weeks.
• Rapamycin and Schwann cells modulated neovasculature, increasing blood vessel number, surface area, and perfusion, which correlated with enhanced axonal regeneration.
• Retrograde axonal tracing confirmed an increased number of descending regenerated axons.

Conclusions:

• Combinatorial hydrogel scaffolds incorporating Schwann cells and sustained rapamycin release effectively promote spinal cord regeneration in rats.
• The strategy normalizes neovascularization, reduces foreign body response, and enhances axonal regeneration, leading to improved functional outcomes.
• This biomaterials-based approach holds potential for future therapeutic strategies targeting spinal cord repair.