The synergetic effect of hydrogel stiffness and growth factor on osteogenic differentiation

Biomaterials. 2014 Jul;35(20):5294-5306. doi: 10.1016/j.biomaterials.2014.02.040. Epub 2014 Apr 3.


Cells respond to various chemical signals as well as environmental aspects of the extracellular matrix (ECM) that may alter cellular structures and functions. Hence, better understanding of the mechanical stimuli of the matrix is essential for creating an adjuvant material that mimics the physiological environment to support cell growth and differentiation, and control the release of the growth factor. In this study, we utilized the property of transglutaminase cross-linked gelatin (TG-Gel), where modification of the mechanical properties of TG-Gel can be easily achieved by tuning the concentration of gelatin. Modifying one or more of the material parameters will result in changes of the cellular responses, including different phenotype-specific gene expressions and functional differentiations. In this study, stiffer TG-Gels itself facilitated focal contact formation and osteogenic differentiation while soft TG-Gel promoted cell proliferation. We also evaluated the interactions between a stimulating factor (i.e. BMP-2) and matrix rigidity on osteogenesis both in vitro and in vivo. The results presented in this study suggest that the interactions of chemical and physical factors in ECM scaffolds may work synergistically to enhance bone regeneration.

Keywords: BMP-2; Cell encapsulation; ECM (extracellular matrix); Mechanical properties; Osteogenesis; Synergetic effect.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Regeneration / drug effects
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Extracellular Matrix / chemistry
  • Gelatin / chemistry
  • Gene Expression
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Mice
  • Osteogenesis / drug effects*
  • Porosity
  • Rats
  • Rats, Inbred F344
  • Transglutaminases / chemistry


  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Hydrogels
  • Gelatin
  • Transglutaminases