PT  - JOURNAL ARTICLE
AU  - Zain Clapacs
AU  - Conor O’Neill
AU  - Paresh Shrimali
AU  - Giriraj Lokhande
AU  - Megan Files
AU  - Darren D. Kim
AU  - Akhilesh Gaharwar
AU  - Jai S. Rudra
TI  - Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation
AID  - 10.1101/2021.11.01.466776
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.01.466776
4099  - http://biorxiv.org/content/early/2021/11/04/2021.11.01.466776.short
4100  - http://biorxiv.org/content/early/2021/11/04/2021.11.01.466776.full
AB  - Alginate hydrogels are widely used for tissue engineering and regenerative medicine due to their excellent biocompatibility. A facile and commonly used strategy to crosslink alginate is the addition of Ca2+ that leads to hydrogelation. However, extracellular Ca2+ is a secondary messenger in activating inflammasome pathways following physical injury or pathogenic insult leading to persistent inflammation and scaffold rejection. Here we present graft copolymers of charge complementary heterodimeric coiled coil (CC) peptides and alginate that undergo supramolecular self-assembly to form Ca2+ free alginate hydrogels. The formation of heterodimeric CCs was confirmed using circular dichroism spectroscopy and scanning electron microscopy revealed a significant difference in pore size between Ca2+ and CC crosslinked gels. The resulting hydrogels were self-supporting and display shear-thinning and shear-recovery properties. In response to lipopolysaccharide (LPS) stimulation, peritoneal macrophages and bone marrow derived dendritic cells cultured in the CC crosslinked gels exhibited a 10-fold reduction in secretion of the proinflammatory cytokine IL-1β compared to Ca2+ crosslinked gels. A similar respose was also observed in vivo upon peritoneal delivery of Ca2+ or CC crosslinked gels. Analysis of peritoneal lavage showed that macrophages in mice injected with Ca2+ crosslinked gels display a more inflammatory phenotype compared to macrophages from mice injected with CC crosslinked gels. These results suggest that CC peptides by virtue of their tunable sequence-structure-function relationship and mild gelation conditions are promising alternative crosslinkers for alginate and other biopolymer scaffolds used in tissue engineering.Competing Interest StatementThe authors have declared no competing interest.