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Nat Mater. 2015 Dec;14(12):1269-77. doi: 10.1038/nmat4407. Epub 2015 Sep 14.

Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation.

Huebsch N1,2,3, Lippens E1,2, Lee K1,2, Mehta M1,2,4,5, Koshy ST1,2,3, Darnell MC1,2, Desai RM1,2, Madl CM1, Xu M1, Zhao X1,6, Chaudhuri O1,2,7, Verbeke C1,2, Kim WS1,2,8, Alim K1, Mammoto A9, Ingber DE1,2,9, Duda GN4,5, Mooney DJ1,2.

Author information

1
Harvard University School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA.
2
Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA.
3
Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
4
Julius Wolff Institute, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
5
Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.
6
Massachusetts Institute of Technology, Department of Mechanical Engineering, Cambridge, Massachusetts 02139, USA.
7
Stanford University Department of Mechanical Engineering, Stanford, California 94305, USA.
8
Department of Plastic Surgery, College of Medicine, Chung-Ang University, Heuk Seok-Dong, Dong Jak-Gu, Seoul 156-755, Korea.
9
Vascular Biology Program, Departments of Pathology &Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

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.

PMID:
26366848
PMCID:
PMC4654683
DOI:
10.1038/nmat4407
[Indexed for MEDLINE]
Free PMC Article

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