Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation

Tissue Eng Part A. 2010 May;16(5):1749-59. doi: 10.1089/ten.TEA.2009.0650.


The purpose of this study was to demonstrate spatial control of osteoblast differentiation in vitro and bone formation in vivo using inkjet bioprinting technology and to create three-dimensional persistent bio-ink patterns of bone morphogenetic protein-2 (BMP-2) and its modifiers immobilized within microporous scaffolds. Semicircular patterns of BMP-2 were printed within circular DermaMatrix human allograft scaffold constructs. The contralateral halves of the constructs were unprinted or printed with BMP-2 modifiers, including the BMP-2 inhibitor, noggin. Printed bio-ink pattern retention was validated using fluorescent or (125)I-labeled bio-inks. Mouse C2C12 progenitor cells cultured on patterned constructs differentiated in a dose-dependent fashion toward an osteoblastic fate in register to BMP-2 patterns. The fidelity of spatial restriction of osteoblastic differentiation at the boundary between neighboring BMP-2 and noggin patterns improved in comparison with patterns without noggin. Acellular DermaMatrix constructs similarly patterned with BMP-2 and noggin were then implanted into a mouse calvarial defect model. Patterns of bone formation in vivo were comparable with patterned responses of osteoblastic differentiation in vitro. These results demonstrate that three-dimensional biopatterning of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Differentiation / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Osteogenesis / drug effects*
  • Skull / drug effects*
  • Skull / growth & development*
  • Tissue Engineering / instrumentation*
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry


  • Bone Morphogenetic Protein 2