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Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation

View ORCID ProfileZain Clapacs, Conor O’Neill, Paresh Shrimali, Giriraj Lokhande, Megan Files, Darren D. Kim, Akhilesh Gaharwar, Jai S. Rudra
doi: https://doi.org/10.1101/2021.11.01.466776
Zain Clapacs
1Department of Biomedical Engineering, Washington University in St. Louis. St. Louis, MO, 63139, USA
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  • ORCID record for Zain Clapacs
Conor O’Neill
1Department of Biomedical Engineering, Washington University in St. Louis. St. Louis, MO, 63139, USA
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Paresh Shrimali
1Department of Biomedical Engineering, Washington University in St. Louis. St. Louis, MO, 63139, USA
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Giriraj Lokhande
2Department of Biomedical Engineering, Texas A&M University College Station, TX, 77840, USA
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Megan Files
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA
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Darren D. Kim
1Department of Biomedical Engineering, Washington University in St. Louis. St. Louis, MO, 63139, USA
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Akhilesh Gaharwar
2Department of Biomedical Engineering, Texas A&M University College Station, TX, 77840, USA
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Jai S. Rudra
1Department of Biomedical Engineering, Washington University in St. Louis. St. Louis, MO, 63139, USA
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  • For correspondence: srudra22@wustl.edu
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ABSTRACT

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 Statement

The authors have declared no competing interest.

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Posted November 04, 2021.
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Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation
Zain Clapacs, Conor O’Neill, Paresh Shrimali, Giriraj Lokhande, Megan Files, Darren D. Kim, Akhilesh Gaharwar, Jai S. Rudra
bioRxiv 2021.11.01.466776; doi: https://doi.org/10.1101/2021.11.01.466776
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Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation
Zain Clapacs, Conor O’Neill, Paresh Shrimali, Giriraj Lokhande, Megan Files, Darren D. Kim, Akhilesh Gaharwar, Jai S. Rudra
bioRxiv 2021.11.01.466776; doi: https://doi.org/10.1101/2021.11.01.466776

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