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Nat Biotechnol. 2016 Mar;34(3):345-52. doi: 10.1038/nbt.3462. Epub 2016 Jan 25.

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.

Author information

1
David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
2
Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
3
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
4
MIT Spectroscopy Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
5
Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
6
Department of Surgery, Division of Transplantation, University of Illinois at Chicago, Chicago, Illinois, USA.
7
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
8
Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
9
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
10
Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Abstract

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.

PMID:
26807527
PMCID:
PMC4904301
DOI:
10.1038/nbt.3462
[Indexed for MEDLINE]
Free PMC Article

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