The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Alginate: Properties and biomedical applications
Lee, K. Y., & Mooney, D. J. (2011) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2011.06.003 · Cited by 8,477
Foreign body reaction to biomaterials
Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.004 · Cited by 5,138
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
On the mechanisms of biocompatibility
Williams, D. F. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.04.023 · Cited by 2,772
Microencapsulated Islets as Bioartificial Endocrine Pancreas
Lim, F., & Sun, A. M. (1980) · Science · doi:10.1126/science.6776628 · Cited by 2,377
Zwitterionic hydrogels implanted in mice resist the foreign-body reaction
Zhang, L., Cao, Z., Bai, T., Carr, L., Ella-Menye, J.-R., Irvin, C., Ratner, B. D., & Jiang, S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2580 · Cited by 1,035
Veiseh, O., Doloff, J. C., Ma, M., Vegas, A. J., Tam, H. H., Bader, A. R., Li, J., Langan, E., Wyckoff, J., Loo, W. S., et al. (2015) · Nature Materials · doi:10.1038/nmat4290 · Cited by 897
Self-citationVegas, A. J., Veiseh, O., Gürtler, M., Millman, J. R., Pagliuca, F. W., Bader, A. R., Doloff, J. C., Li, J., Chen, M., Olejnik, K., et al. (2016) · Nature Medicine · doi:10.1038/nm.4030 · Cited by 710
Self-citationProangiogenic scaffolds as functional templates for cardiac tissue engineering
Madden, L. R., Mortisen, D. J., Sussman, E. M., Dupras, S. K., Fugate, J. A., Cuy, J. L., Hauch, K. D., Laflamme, M. A., Murry, C. E., & Ratner, B. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006442107 · Cited by 662
Pharmacological significance of triazole scaffold
Kharb, R., Sharma, P. C., & Yar, M. S. (2010) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.3109/14756360903524304 · Cited by 612
Neovascularization of synthetic membranes directed by membrane microarchitecture
Brauker, J. H., Carr‐Brendel, V. E., Martinson, L. A., Crudele, J., Johnston, W. D., & Johnson, R. C. (1995) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820291208 · Cited by 517
Alginate-based microcapsules for immunoisolation of pancreatic islets
de Vos, P., Faas, M. M., Strand, B. L., & Calafiore, R. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.07.010 · Cited by 511
Sussman, E. M., Halpin, M. C., Muster, J., Moon, R. T., & Ratner, B. D. (2014) · Annals of Biomedical Engineering · doi:10.1007/s10439-013-0933-0 · Cited by 416
Sato, M., Sano, H. I., Iwaki, D., Kudo, K., Konishi, M., Takahashi, H., Takahashi, T., Imaizumi, H., Asai, Y., & Kuroki, Y. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.417 · Cited by 348
Wick, G., Grundtman, C., Mayerl, C., Wimpissinger, F., Feichtinger, J., Zelger, B. G., Sgonc, R., & Wolfram, D. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095937 · Cited by 347
Biocompatibility of alginate–poly-l-lysine microcapsules for cell therapy
Orive, G., Tam, S. K., Pedraz, J. L., & Hallé, J. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.02.048 · Cited by 338
Ward, W. K. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200504 · Cited by 337
Safety and Viability of Microencapsulated Human Islets Transplanted Into Diabetic Humans
Tuch, B., Keogh, G., Williams, L., Wu, W., Foster, J., Vaithilingam, V., & Philips, R. (2009) · Diabetes Care · doi:10.2337/dc09-0744 · Cited by 329
Scharp, D. W., & Marchetti, P. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.07.018 · Cited by 314
Macroscale delivery systems for molecular and cellular payloads
Kearney, C. J., & Mooney, D. J. (2013) · Nature Materials · doi:10.1038/nmat3758 · Cited by 302
Duvivier-Kali, V. F., Omer, A., Parent, R. J., O’Neil, J. J., & Weir, G. C. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1698 · Cited by 292
Self-citationReducing capsular thickness and enhancing angiogenesis around implant drug release systems
Ratner, B. D. (2002) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00502-8 · Cited by 271
Combating medical device fouling
Harding, J. L., & Reynolds, M. M. (2014) · Trends in biotechnology · doi:10.1016/j.tibtech.2013.12.004 · Cited by 269
Jacobs‐Tulleneers‐Thevissen, D., Chintinne, M., Ling, Z., Gillard, P., Schoonjans, L., Delvaux, G., Strand, B. L., Gorus, F., Keymeulen, B., & PIPELEERS, D. G. (2013) · Diabetologia · doi:10.1007/s00125-013-2906-0 · Cited by 238
Multiscale requirements for bioencapsulation in medicine and biotechnology
de Vos, P., Bučko, M., Gemeiner, P., Navrátil, M., Švitel, J., Faas, M. M., Strand, B. L., Skjåk‐Bræk, G., Mørch, Y. A., Vikartovská, A., et al. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.01.014 · Cited by 210
All charged up about implanted biomaterials
Grainger, D. W. (2013) · Nature Biotechnology · doi:10.1038/nbt.2600 · Cited by 187
Dusseault, J., Tam, S. K., Ménard, M., Polizu, S., Jourdan, G., Yahia, L., & Hallé, J. (2005) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30541 · Cited by 169
Perspectives and Challenges in Tissue Engineering and Regenerative Medicine
Langer, R. (2009) · Advanced Materials · doi:10.1002/adma.200902589 · Cited by 161
Self-citationReduced foreign body response at nitric oxide-releasing subcutaneous implants
Hetrick, E. M., Prichard, H. L., Klitzman, B., & Schoenfisch, M. H. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.06.036 · Cited by 158
Bernhardt, A., Markus, W., Paul, B., Hochmuth, T., Schumacher, M., Schütz, K., & Gelinsky, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129205 · Cited by 157
Omer, A., Duvivier-Kali, V. F., Trivedi, N., Wilmot, K., Bonner‐Weir, S., & Weir, G. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.69 · Cited by 136
Self-citationFibrinogen adsorption and host tissue responses to plasma functionalized surfaces
Tang, L., Wu, Y., & Timmons, R. B. (1998) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(199810)42:1 · Cited by 127
Dang, T. T., Thai, A. V., Cohen, J., Slosberg, J. E., Siniakowicz, K., Doloff, J. C., Ma, M., Hollister-Lock, J., Tang, K. M., Gu, Z., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.016 · Cited by 125
Self-citationLong-Term Normoglycemia in Rats Receiving Transplants with Encapsulated Islets
Omer, A., Duvivier-Kali, V. F., Fernandes, J. R., Tchipashvili, V., Colton, C. K., & Weir, G. C. (2004) · Transplantation · doi:10.1097/01.tp.0000149340.37865.46 · Cited by 112
Self-citationKim, K., Cheng, J., Liu, Q., Wu, X. Y., & Sun, Y. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32338 · Cited by 112
Quantitative in vivo cytokine analysis at synthetic biomaterial implant sites
Rodriguez, A., Meyerson, H., & Anderson, J. M. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31939 · Cited by 111
Rokstad, A. M., Brekke, O., Steinkjer, B., Ryan, L., Kolláriková, G., Strand, B. L., Skjåk‐Bræk, G., Lacı́k, I., Espevik, T., & Mollnes, T. E. (2011) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.03.011 · Cited by 105
Combined confocal Raman and quantitative phase microscopy system for biomedical diagnosis
Kang, J. W., Lue, N., Kong, C.-R., Barman, I., Dingari, N. C., Goldfless, S. J., Niles, J. C., Dasari, R. R., & Feld, M. S. (2011) · Biomedical Optics Express · doi:10.1364/boe.2.002484 · Cited by 100
Self-citationHigh-throughput quantification of hydroxyproline for determination of collagen
Hofman, K., Hall, B., Cleaver, H., & Marshall, S. N. (2011) · Analytical Biochemistry · doi:10.1016/j.ab.2011.06.019 · Cited by 99
Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging
Haller, J., Hyde, D. E., Deliolanis, N. C., de Kleine, R. H. J., Niedre, M. J., & Ntziachristos, V. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00959.2007 · Cited by 96
Terminal sterilization of alginate hydrogels: Efficacy and impact on mechanical properties
Stoppel, W. L., White, J. C., Horava, S. D., Henry, A. C., Roberts, S. C., & Bhatia, S. R. (2013) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.33070 · Cited by 94
Molecular Imaging of Innate Immune Cell Function in Transplant Rejection
Christen, T., Nahrendorf, M., Wildgruber, M., Świrski, F. K., Aïkawa, E., Waterman, P. R., Shimizu, K., Weissleder, R., & Libby, P. (2009) · Circulation · doi:10.1161/circulationaha.108.796888 · Cited by 93
Islet encapsulation: advances and obstacles
Weir, G. C. (2013) · Diabetologia · doi:10.1007/s00125-013-2921-1 · Cited by 82
Self-citationRole of protein contaminants in the immunogenicity of alginates
Ménard, M., Dusseault, J., Langlois, G., Baille, W. E., Tam, S. K., Yahia, L., Zhu, X. X., & Hallé, J. (2010) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.31570 · Cited by 78
Timp-1 is a Key Factor of Fibrogenic Response to Bleomycin in Mouse Lung
Manoury, B., Caulet-Maugendre, S., Guénon, I., Lagente, V., & Boichot, E. (2006) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200601900303 · Cited by 77
Inflammatory response to peritoneal implantation of alginate–poly-l-lysine microcapsules
Robitaille, R., Dusseault, J., Henley, N., Desbiens, K., Labrecque, N., & Hallé, J. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.10.028 · Cited by 68
Paredes-Juarez, G. A., de Haan, B. J., Faas, M. M., & de Vos, P. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.09.009 · Cited by 68
A Technology Platform to Test the Efficacy of Purification of Alginate
Paredes-Juarez, G. A., de Haan, B., Faas, M. M., & de Vos, P. (2014) · Materials · doi:10.3390/ma7032087 · Cited by 67
Rapid Biocompatibility Analysis of Materials via In Vivo Fluorescence Imaging of Mouse Models
Bratlie, K. M., Dang, T. T., Lyle, S. R., Nahrendorf, M., Weissleder, R., Langer, R., & Anderson, D. G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010032 · Cited by 64
Self-citationLiu, M., Yue, X., Dai, Z., Xing, L., Ma, F., & Ren, N. (2007) · Langmuir · doi:10.1021/la7002996 · Cited by 54
Kang, J. W., Nguyen, F. T., Lue, N., Dasari, R. R., & Heller, D. A. (2012) · Nano Letters · doi:10.1021/nl302991y · Cited by 42
Self-citationQi, M., Lacı́k, I., Kolláriková, G., Strand, B. L., Formo, K., Wang, Y., Marchese, E., Mendoza-Elias, J. E., Kinzer, K. P., Gatti, F., et al. (2011) · Journal of Surgical Research · doi:10.1016/j.jss.2011.01.040 · Cited by 33
Self-citationCombinatorial synthesis with high throughput discovery of protein-resistant membrane surfaces
Gu, M., Vegas, A. J., Anderson, D. G., Langer, R., Kilduff, J. E., & Belfort, G. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.051 · Cited by 30
Self-citationde Haan, B. J., Rossi, A., Faas, M. M., Smelt, M. J., Sonvico, F., Colombo, P., & de Vos, P. (2011) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.33123 · Cited by 29
Lindstedt, R., Ruggiero, V., D’Alessio, V., Manganello, S., Petronzelli, F., Stasi, M. A., Vendetti, S., Assandri, A., Carminati, P., & Santis, R. D. (2009) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200902200105 · Cited by 14
Vegas, A. J., Omid Veiseh, A., Madsörtler, G., Millman, J. R., Pagliuca, F. W., Bader, A., Doloff, J. C., Li, J., Chen, M. J., Olejnik, K. T., et al. (2016) · Nature Medicine · doi:10.1038/nm0416-446e · Cited by 14
Self-citationShen, M., & Horbett, T. A. (2001) · Journal of Biomedical Materials Research · doi:10.1002/1097-4636(20011205)57:3
Flagged first, then by citations
Cited by
Sorted by citations
The evolution of commercial drug delivery technologies
Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361
Cao, H., Duan, L., Zhang, Y., Cao, J., & Zhang, K. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00830-x · Cited by 1,380
Translational Applications of Hydrogels
Correa, S., Grosskopf, A. K., Hernandez, H. L., Chan, D. C., Yu, A. C., Stapleton, L. M., & Appel, E. A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01177 · Cited by 1,174
Liu, X., Liu, J., Lin, S., & Zhao, X. (2020) · Materials Today · doi:10.1016/j.mattod.2019.12.026 · Cited by 1,023
3D printing of hydrogels: Rational design strategies and emerging biomedical applications
Li, J., Wu, C., Chu, P. K.-H., & Gelinsky, M. (2020) · Materials Science and Engineering R Reports · doi:10.1016/j.mser.2020.100543 · Cited by 899
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
