Cell and Tissue Research

, Volume 344, Issue 3, pp 499–509 | Cite as

Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels

  • Nathaniel S. Hwang
  • Shyni Varghese
  • Hanwei Li
  • Jennifer ElisseeffEmail author
Regular Article


Bone-marrow-derived mesenchymal stem cells (MSCs) are candidates for regeneration applications in musculoskeletal tissue such as cartilage and bone. Various soluble factors in the form of growth factors and cytokines have been widely studied for directing the chondrogenic and osteogenic differentiation of MSCs, but little is known about the way that the composition of extracellular matrix (ECM) components in three-dimensional microenvironments plays a role in regulating the differentiation of MSCs. To define whether ECM components influence the regulation of osteogenic and chondrogenic differentiation by MSCs, we encapsulated MSCs in poly-(ethylene glycol)-based (PEG-based) hydrogels containing exogenous type I collagen, type II collagen, or hyaluronic acids (HA) and cultured them for up to 6 weeks in chondrogenic medium containing transforming growth factor-β1 (10 ng/ml) or osteogenic medium. Actin cytoskeleton organization and cellular morphology were strongly dependent on which ECM components were added to the PEG-based hydrogels. Additionally, chondrogenic differentiation of MSCs was marginally enhanced in collagen-matrix-based hydrogels, whereas osteogenic differentiation, as measured by calcium accumulation, was induced in HA-containing hydrogels. Thus, the microenvironments created by exogenous ECM components seem to modulate the fate of MSC differentiation.


Extracellular microenvironment Osteogenesis Chondrogenesis Mesenchymal stem cells Hyaluronic acids Type I collagen Type II collagen Goat 



The authors are grateful to Dr. Zijun Zhang (St. Louis University, Department of Orthopedic Surgery) for critical review and to Dr. Rober E. Allen (Johns Hopkins University, Department of Biomedical Engineering) for access to the Instron Universal Testing Machine.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Nathaniel S. Hwang
    • 1
    • 3
  • Shyni Varghese
    • 2
  • Hanwei Li
    • 1
  • Jennifer Elisseeff
    • 1
    Email author
  1. 1.Wilmer Eye Institute and Department of Biomedical EngineeringJohns Hopkins School of MedicineBaltimoreUSA
  2. 2.Department of BioengineeringUniversity of California at San DiegoLa JollaUSA
  3. 3.David H. Koch Institute for Integrative Cancer ResearchMassachusetts Institute of TechnologyCambridgeUSA

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