In vitro evaluation of an injectable biphasic calcium phosphate (BCP) carrier system combined with recombinant human bone morphogenetic protein (rhBMP)-9

Biomed Mater Eng. 2017;28(3):293-304. doi: 10.3233/BME-171675.


Bone morphogenetic protein 9 (BMP9) has previously been characterized as the strongest osteoinductive growth factor among the BMP family. The aim of the present study was to evaluate the possibility of combining rhBMP9 with an injectable biphasic calcium phosphate (I-BCP, maxresorb inject®), since I-BCP is an easy to handle biomaterial with ideal properties for bone augmentation procedures. The adsorption potential of rhBMP9 as well as the cell behavior of bone stromal ST2 cells were investigated on cell viability, adhesion, proliferation and osteogenic differentiation for I-BCP combined with/without rhBMP9 in vitro. I-BCP demonstrated excellent adsorption/retention potential of rhBMP9 with a slow and steady release over a 10 day period by ELISA. Cell attachment at 8 hours and cell proliferation at 1, 3 and 5 days was decreased on I-BCP with/without rhBMP9 when compared to control tissue-culture plastic. While I-BCP had little influence on osteoblast differentiation, its combination with rhBMP9 significantly increased ALP activity at 7 days and mRNA levels of osteoblast differentiation markers including ALP and osteocalcin at 14 days. I-BCP served as an excellent carrier for rhBMP9 clearly demonstrating its osteoinductive potential. We therefore confirm the great potential of rhBMP9 to serve as a future regenerative growth factor for bone applications.

Keywords: BCP; BMP9; Bone morphogenetic proteins; biphasic calcium phosphate; bone augmentation; bone regeneration; carrier system; osteogenesis.

MeSH terms

  • Bone Morphogenetic Proteins / administration & dosage
  • Bone Morphogenetic Proteins / chemistry*
  • Cell Differentiation
  • Cell Line
  • Growth Differentiation Factor 2 / administration & dosage
  • Growth Differentiation Factor 2 / chemistry
  • Humans
  • Hydroxyapatites / chemistry*
  • Osteoblasts / drug effects*
  • Osteogenesis / drug effects*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry


  • Bone Morphogenetic Proteins
  • Growth Differentiation Factor 2
  • Hydroxyapatites
  • Recombinant Proteins
  • hydroxyapatite-beta tricalcium phosphate