Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat Mater 2015 Dec;14(12):1269-77
Date
09/15/2015Pubmed ID
26366848Pubmed Central ID
PMC4654683DOI
10.1038/nmat4407Scopus ID
2-s2.0-84947868969 (requires institutional sign-in at Scopus site) 463 CitationsAbstract
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.
Author List
Huebsch N, Lippens E, Lee K, Mehta M, Koshy ST, Darnell MC, Desai RM, Madl CM, Xu M, Zhao X, Chaudhuri O, Verbeke C, Kim WS, Alim K, Mammoto A, Ingber DE, Duda GN, Mooney DJAuthor
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biocompatible MaterialsBone Development
Elasticity
Extracellular Matrix
Hydrogels
Mesenchymal Stem Cell Transplantation
