title: Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation.
abstract: The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Huebsch
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
authors.forename: Evi
authors.initials: E
authors.lastname: Lippens
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
authors.forename: Kangwon
authors.initials: K
authors.lastname: Lee
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.|Julius Wolff Institute, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.
authors.forename: Manav
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Sandeep T
authors.initials: ST
authors.lastname: Koshy
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
authors.forename: Max C
authors.initials: MC
authors.lastname: Darnell
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
authors.forename: Rajiv M
authors.initials: RM
authors.lastname: Desai
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Madl
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Xu
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Massachusetts Institute of Technology, Department of Mechanical Engineering, Cambridge, Massachusetts 02139, USA.
authors.forename: Xuanhe
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.|Stanford University Department of Mechanical Engineering, Stanford, California 94305, USA.
authors.forename: Ovijit
authors.initials: O
authors.lastname: Chaudhuri
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
authors.forename: Catia
authors.initials: C
authors.lastname: Verbeke
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.|Department of Plastic Surgery, College of Medicine, Chung-Ang University, Heuk Seok-Dong, Dong Jak-Gu, Seoul 156-755, Korea.
authors.forename: Woo Seob
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Alim
authors.affiliation: Vascular Biology Program, Departments of Pathology &Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mammoto
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.|Vascular Biology Program, Departments of Pathology &Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
authors.affiliation: Julius Wolff Institute, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D001672:Biocompatible Materials; D001846:Bone Development; D004548:Elasticity; D005109:Extracellular Matrix / Q000502:physiology*; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels