Modular poly(ethylene glycol) matrices for the controlled 3D-localized osteogenic differentiation of mesenchymal stem cells

Adv Healthc Mater. 2015 Mar 11;4(4):550-8. doi: 10.1002/adhm.201400547. Epub 2014 Oct 31.


The in vitro formation of physiologically relevant engineered tissues is still limited by the availability of adequate growth-factor-presenting cell-instructive biomaterials, allowing simultaneous and three-dimensionally localized differentiation of multiple tissue progenitor cells. Together with ever improving technologies such as microfluidics, printing, or lithography, these biomaterials could provide the basis for generating provisional cellular constructs, which can differentiate to form tissue mimetics. Although state-of-the-art biomaterials are endowed with sophisticated modules for time- and space-controlled positioning and release of bioactive molecules, reports on 3D arrangements of differentiation-inducing growth factors are scarce. This paper describes the stable and localized immobilization of biotinylated bioactive molecules to a modular, Factor XIII-cross-linked poly(ethylene glycol) hydrogel platform using a genetically engineered streptavidin linker. Linker incorporation is demonstrated by Western blot, and streptavidin functionality is confirmed by capturing biotinylated alkaline phosphatase (ALP). After optimizing bone morphogenetic protein 2 (BMP-2) biotinylation, streptavidin-modified hydrogels are able to bind and present bioactive BMP-2-biotin. Finally, with this immobilization scheme for BMP-2, the specific osteogenic differentiation of mesenchymal stem cells is demonstrated by inducing ALP expression in confined 3D areas. In future, this platform together with other affinity-based strategies will be useful for the local incorporation of various growth factors for engineering cell-responsive constructs.

Keywords: biomimetic matrices; bone morphogenetic protein-2; growth factor delivery; protein positioning; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotin / chemistry
  • Biotin / metabolism
  • Biotinylation
  • Bone Morphogenetic Protein 2 / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Line
  • Glutamine / chemistry
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology
  • Immobilized Proteins / pharmacology
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Osteogenesis / drug effects*
  • Polyethylene Glycols / pharmacology*
  • Recombinant Proteins / pharmacology
  • Streptavidin / chemistry
  • Transforming Growth Factor beta / pharmacology


  • Bone Morphogenetic Protein 2
  • Immobilized Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Glutamine
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyethylene Glycols
  • Biotin
  • Streptavidin