Polysialic Acid-Functionalized MAP Scaffolds Promote Regulatory Immune Responses After Ischemic Stroke

Area of Science:

• Neuroscience
• Biomaterials Science
• Immunology

Background:

• Glycosylation regulates CNS immune and neural functions.
• Biomaterials often overlook glycans due to complexity.
• Polysialic acid (PSA) shows potential for immunomodulation via Siglec interactions.

Purpose of the Study:

• To engineer a biomaterial scaffold presenting PSA for CNS injury treatment.
• To evaluate the efficacy of PSA-presenting scaffolds in a stroke model.

Main Methods:

• Screening of sialic acid derivatives to identify PSA's anti-inflammatory properties.
• Engineering injectable microporous annealed particle (MAP) scaffolds presenting covalently immobilized PSA (MAP-PSA).
• Assessing MAP-PSA in an ischemic stroke model in vivo.

Main Results:

• PSA uniquely induced anti-inflammatory polarization in macrophages (BMDMs).
• MAP-PSA scaffolds demonstrated mechanical stability and resistance to degradation.
• MAP-PSA reduced neutrophil infiltration and inflammation post-stroke.
• MAP-PSA enhanced reparative macrophage and microglial phenotypes, improving homeostasis.

Conclusions:

• MAP-PSA scaffolds represent a novel therapeutic approach for CNS injuries like stroke.
• The immunomodulatory effects of MAP-PSA are sustained into subacute stages.
• These findings suggest broad translational potential for neuroinflammatory and regenerative applications.