RT Journal Article
SR Electronic
T1 Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.01.466776
DO 10.1101/2021.11.01.466776
A1 Zain Clapacs
A1 Conor O’Neill
A1 Paresh Shrimali
A1 Giriraj Lokhande
A1 Megan Files
A1 Darren D. Kim
A1 Akhilesh Gaharwar
A1 Jai S. Rudra
YR 2021
UL http://biorxiv.org/content/early/2021/11/04/2021.11.01.466776.abstract
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.