title: Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.
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.
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Arturo J
authors.initials: AJ
authors.lastname: Vegas
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Veiseh
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Doloff
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Minglin
authors.initials: M
authors.lastname: Ma
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Hok Hei
authors.initials: HH
authors.lastname: Tam
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Kaitlin
authors.identifier: 0000-0002-5197-0176
authors.initials: K
authors.lastname: Bratlie
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Bader
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Langan
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Olejnik
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Fenton
authors.affiliation: MIT Spectroscopy Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Jeon Woong
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hollister-Locke
authors.affiliation: Department of Surgery, Division of Transplantation, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Bochenek
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Chiu
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Siebert
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tang
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Aresta-Dasilva
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Nimit
authors.initials: N
authors.lastname: Dholakia
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Thakrar
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Thema
authors.initials: T
authors.lastname: Vietti
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Michael
authors.identifier: 0000-0002-1590-768X
authors.initials: M
authors.lastname: Chen
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Karolina
authors.initials: K
authors.lastname: Siniakowicz
authors.affiliation: Department of Surgery, Division of Transplantation, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Meirigeng
authors.initials: M
authors.lastname: Qi
authors.affiliation: Department of Surgery, Division of Transplantation, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: James
authors.initials: J
authors.lastname: McGarrigle
authors.forename: Adam C
authors.initials: AC
authors.lastname: Graham
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lyle
authors.affiliation: Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Harlan
authors.affiliation: Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: Department of Surgery, Division of Transplantation, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000627:therapeutic use; D005547:Foreign Bodies / Q000276:immunology*; D005549:Foreign-Body Reaction / Q000276:immunology*; D006801:Humans; D020100:Hydrogels / Q000009:adverse effects / Q000627:therapeutic use*; D008264:Macrophages / Q000276:immunology; D011323:Primates / Q000276:immunology; D019736:Prostheses and Implants / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels