title: Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates.
abstract: The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [3] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Veiseh
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Doloff
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA [3] Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA.
authors.forename: Minglin
authors.initials: M
authors.lastname: Ma
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Arturo J
authors.initials: AJ
authors.lastname: Vegas
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Hok Hei
authors.initials: HH
authors.lastname: Tam
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Bader
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Langan
authors.affiliation: David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wyckoff
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Loo
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Chiu
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Siebert
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tang
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hollister-Lock
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Aresta-Dasilva
authors.affiliation: Division of Transplantation, Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bochenek
authors.affiliation: Division of Transplantation, Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Mendoza-Elias
authors.affiliation: Division of Transplantation, Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Transplantation, Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Merigeng
authors.initials: M
authors.lastname: Qi
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Danya M
authors.initials: DM
authors.lastname: Lavin
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chen
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Nimit
authors.initials: N
authors.lastname: Dholakia
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Thakrar
authors.affiliation: Department for Biomaterials Research, Polymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9, 845 41 Bratislava, Slovakia.
authors.forename: Igor
authors.initials: I
authors.lastname: Lacík
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.affiliation: Division of Transplantation, Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [3] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA [4] Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [5] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [6] Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: 1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [3] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA [4] Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [5] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [6] Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D005549:Foreign-Body Reaction / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011323:Primates