Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

Qingsheng Liu, Alan Chiu, Long-Hai Wang, Duo An, Monica Zhong, Alexandra M. Smink, Bart J. Haan, Paul Vos, Kevin Keane, Andreas Vegge, Esther Y. Chen, Wei Song, Wendy F. Liu, James Flanders, Claude Rescan, Lars Groth Grunnet, Xi Wang and Minglin Ma ()
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Qingsheng Liu: Cornell University
Alan Chiu: Cornell University
Long-Hai Wang: Cornell University
Duo An: Cornell University
Monica Zhong: Cornell University
Alexandra M. Smink: University of Groningen and University Medical Center Groningen
Bart J. Haan: University of Groningen and University Medical Center Groningen
Paul Vos: University of Groningen and University Medical Center Groningen
Kevin Keane: Stem Cell Biology, Novo Nordisk A/S
Andreas Vegge: Diabetes Research, Novo Nordisk A/S
Esther Y. Chen: University of California Irvine
Wei Song: Cornell University
Wendy F. Liu: University of California Irvine
James Flanders: Cornell University
Claude Rescan: Stem Cell Pharmacology, Novo Nordisk A/S
Lars Groth Grunnet: Stem Cell Pharmacology, Novo Nordisk A/S
Xi Wang: Cornell University
Minglin Ma: Cornell University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.

Date: 2019
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DOI: 10.1038/s41467-019-13238-7

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