Microporous annealed particle scaffolds avoid foreign body response by down regulating...

Area of Science:

• Biomaterials Science
• Immunology
• Tissue Engineering

Background:

• Biomaterial implantation often elicits a foreign body response (FBR), hindering successful tissue integration.
• Understanding how material properties, such as porosity, influence the FBR is crucial for designing effective medical implants.

Purpose of the Study:

• To investigate the impact of implant porosity on the immune response and tissue integration following subcutaneous implantation.
• To compare the FBR induced by microporous annealed particle (MAP) scaffolds versus nanoporous hydrogels.

Main Methods:

• Utilized mass cytometry, single-cell RNA sequencing, and multiplex cytokine assays to analyze immune cell populations and cytokine profiles.
• Compared subcutaneous implants of MAP scaffolds and nanoporous hydrogels in mice.
• Investigated the role of the complement system, including C5a signaling, and used C5-deficient mice for validation.

Main Results:

• MAP scaffolds promoted vascularization and tissue integration, characterized by increased endothelial cells, regulatory T cells, and reduced pro-inflammatory cytokines.
• Nanoporous hydrogels induced an FBR characterized by enrichment of basophils, natural killer cells, and pro-fibrotic macrophage populations.
• MAP scaffolds suppressed the complement-fibroblast-macrophage signaling loop, particularly C5a signaling, which was not observed with nanoporous hydrogels.

Conclusions:

• Scaffold porosity is a critical determinant of the immune and complement response to biomaterials.
• MAP scaffolds effectively mitigate the foreign body response by modulating immune cell infiltration and suppressing key inflammatory signaling pathways.
• These findings provide a mechanistic understanding for improved biomaterial integration using MAP scaffolds.