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Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates
Open accessAbstract
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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“For example, a combinatorial biomaterial screen identified three different triazole-containing covalent modifications to alginate that significantly reduced the foreign body response in both rodents and non-human primates.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [104]
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Metadata
- 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
- Venue
- Nature Biotechnology
- Published
- 2016-01-25
- Volume
- 34
- Issue
- 3
- Pages
- 345-352
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- 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
- 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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