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

Arturo J. Vegas, Omid Veiseh, Joshua C. Doloff, Minglin Ma, Hok Hei Tam, Kaitlin Bratlie, Jie Li, Andrew R. Bader, Erin Langan, Karsten Olejnik, Patrick Fenton, Jeon Woong Kang, Jennifer Hollister-Locke, Matthew A. Bochenek, Alan Chiu, Sean Siebert, Katherine Tang, Siddharth Jhunjhunwala, Stephanie Aresta-Dasilva, Nimit DholakiaRaj Thakrar, Thema Vietti, Michael Chen, Josh Cohen, Karolina Siniakowicz, Meirigeng Qi, James McGarrigle, Stephen Lyle, David M. Harlan, Dale L. Greiner, Jose Oberholzer, Gordon C. Weir, Robert Langer, Daniel G. Anderson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)345-352
Number of pages8
JournalNature biotechnology
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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