Cited by 551Hydrogels: synthesis, properties, applicationsPolymer Surface Interaction StudiesTissue Engineering and Regenerative Medicine

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

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Vegas, Arturo J, Veiseh, Omid, Doloff, Joshua C, Ma, Minglin, Tam, Hok Hei, Bratlie, Kaitlin, Li, Jie, Bader, Andrew R, Langan, Erin, Olejnik, Karsten, Fenton, Patrick, Kang, Jeon Woong, Hollister-Locke, Jennifer, Bochenek, Matthew A, Chiu, Alan, Siebert, Sean, Tang, Katherine, Jhunjhunwala, Siddharth, Aresta-Dasilva, Stephanie, Dholakia, Nimit, Thakrar, Raj, Vietti, Thema, Chen, Michael, Cohen, Josh, Siniakowicz, Karolina, Qi, Meirigeng, McGarrigle, James, Graham, Adam C, Lyle, Stephen, Harlan, David M, Greiner, Dale L, Oberholzer, Jose, Weir, Gordon C, Langer, Robert, Anderson, Daniel G·2016·Nature Biotechnology

DOI 10.1038/nbt.3462PMC PMC4904301

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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.

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Authors: Vegas, A. J., Veiseh, O., Doloff, J. C., Ma, M., Tam, H. H., Bratlie, K., Li, J., Bader, A. R., Langan, E., Olejnik, K., Fenton, P., Kang, J. W., Hollister-Locke, J., Bochenek, M. A., Chiu, A., Siebert, S., Tang, K., Jhunjhunwala, S., Aresta-Dasilva, S., Dholakia, N., Thakrar, R., Vietti, T., Chen, M., Cohen, J., Siniakowicz, K., Qi, M., McGarrigle, J., Graham, A. C., Lyle, S., Harlan, D. M., Greiner, D. L., Oberholzer, J., Weir, G. C., Langer, R., & Anderson, D. G.
Affiliations: Boston Children's Hospital (US)
Koch Institute for Integrative Cancer Research At MIT (US)
Massachusetts Institute of Technology (US)
University of Illinois Chicago (US)
Joslin Diabetes Center (US)
Harvard University (US)
University of Massachusetts Chan Medical School (US)
Corresponding author: Anderson, Daniel G
ORCID: Vegas, Arturo J
Doloff, Joshua C
Ma, Minglin
Tam, Hok Hei
Bratlie, Kaitlin
Langan, Erin
Kang, Jeon Woong
Bochenek, Matthew A
Tang, Katherine
Jhunjhunwala, Siddharth
Chen, Michael
Qi, Meirigeng
McGarrigle, James
Graham, Adam C
Lyle, Stephen
Harlan, David M
Greiner, Dale L
Weir, Gordon C
Anderson, Daniel G
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2016-01-25
Volume: 34
Issue: 3
Pages: 345-352
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt.3462
PMC: PMC4904301
OpenAlex: W2260141621
Cited by: 551
References: 57
Citations by year: 2026: 41 · 2025: 42 · 2024: 58 · 2023: 56 · 2022: 54 · 2021: 71 · 2020: 61 · 2019: 50 · 2018: 55 · 2017: 32 · 2016: 31
FWCI: 27.32
Type: journal article
Language: en
Update notices: erratum (2016-06-09)
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Iowa State University Digital Repository (Iowa State University) (submittedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
Funders: U.S. Department of Defense (P30-CA14051, W81XWH, W81XWH1310215, W81XWH-13)
Leona M. and Harry B. Helmsley Charitable Trust
Harvard University
Joslin Diabetes Center (P30DK036836)
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (P30-CA14051)
Diabetes Research and Wellness Foundation
Skolkovo Institute of Science and Technology
National Institutes of Health (4r37eb000244-34, W81XWH, CA151884, EB-000244)
Diabetes Research Center (P30 DK 036836)
National Cancer Institute (U54CA151884, CA14051, CA151884, P30CA014051, P30-CA-14051)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091526, R01DK093909, P30DK036836)
National Institute of Biomedical Imaging and Bioengineering (EB-000244, R01EB000244, R37-EB000244, P41EB015871, EB 000351, R01EB000351)
National Institute of Dental and Craniofacial Research (DE013023, R01DE013023)
Congressionally Directed Medical Research Programs
Topics: Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords: foreign body reaction, alginate hydrogel, combinatorial libraries, biomaterials, biomedical implants, macrophage recognition, non-human primates, biocompatibility
MeSH terms: Animals, Biocompatible Materials, Foreign Bodies, Foreign-Body Reaction, Humans, Macrophages, Primates, Prostheses and Implants, Hydrogels

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

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