Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Alginate hydrogels are widely used in tissue engineering due to their biocompatibility.
• Traditional calcium (Ca2+) crosslinking poses risks of inflammation and scaffold rejection due to Ca2+s role as a signaling molecule.

Purpose of the Study:

• To develop novel calcium-free alginate hydrogels using self-assembling charge-complementary heterodimeric coiled coil (CC) peptides.
• To evaluate the inflammatory response and in vivo performance of CC-crosslinked alginate hydrogels compared to Ca2+-crosslinked hydrogels.

Main Methods:

• Graft copolymers of CC peptides and alginate were synthesized.
• Hydrogel formation was characterized using circular dichroism spectroscopy and scanning electron microscopy.
• In vitro inflammatory response was assessed using peritoneal macrophages and dendritic cells stimulated with lipopolysaccharide (LPS).
• In vivo inflammatory response was evaluated in mice following peritoneal delivery of hydrogels.

Main Results:

• CC peptides successfully formed Ca2+-free alginate hydrogels with distinct crosslinking properties compared to Ca2+-crosslinked gels.
• CC-crosslinked hydrogels exhibited shear-thinning and shear-recovery properties.
• Cells cultured in CC-crosslinked gels showed a 10-fold reduction in the pro-inflammatory cytokine IL-1β secretion compared to Ca2+-crosslinked gels.
• In vivo studies demonstrated a less inflammatory phenotype in macrophages from mice treated with CC-crosslinked hydrogels.

Conclusions:

• Charge-complementary heterodimeric coiled coil peptides provide a viable, Ca2+-free crosslinking strategy for alginate hydrogels.
• These CC-peptide crosslinked hydrogels significantly reduce inflammatory responses both in vitro and in vivo.
• CC peptides represent a promising alternative to Ca2+ for developing safer and more effective biopolymer scaffolds in tissue engineering and regenerative medicine.