An in vitro study of fibrin sealant as a carrier system for recombinant human bone morphogenetic protein (rhBMP)-9 for bone tissue engineering

J Craniomaxillofac Surg. 2017 Jan;45(1):27-32. doi: 10.1016/j.jcms.2016.10.008. Epub 2016 Oct 20.


In the craniofacial bone field, fibrin sealants are used as coagulant and adhesive tools to stabilize grafts during surgery. Despite this, their exact role in osteogenesis is poorly characterized. In the present study, we aimed to characterize the osteogenic potential of TISSEEL fibrin sealant and used its technology to incorporate growth factors within its matrix. We focused on recombinant human bone morphogenetic protein (rhBMP)-9, which has previously been characterized as one of the strongest osteogenetic inducers in the BMP family. TISSEEL displayed an excellent ability to retain rhBMP9, which was gradually released over a 10-day period. Although TISSEEL decreased bone stromal ST2 cell attachment at 8 h, it displayed normal cell proliferation at 1, 3, and 5 days when compared to tissue culture plastic. Interestingly, TISSEEL had little influence on osteoblast differentiation; however its combination with rhBMP9 significantly increased ALP activity at 7 days, Alizarin Red staining at 14 days, and mRNA levels of osteoblast differentiation markers ALP, bone sialoprotein, and osteocalcin. In summary, although fibrin sealants were shown to have little influence on osteogenesis, their combination with bone-inducing growth factors such as rhBMP9 may serve as an attractive carrier/scaffold for future bone regenerative strategies. Future animal studies are now necessary.

Keywords: BMP9; Bone morphogenetic proteins; Bone regeneration; Fibrin glue; Fibrin sealant; Osteogenesis.

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Drug Carriers / administration & dosage
  • Drug Carriers / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Fibrin Tissue Adhesive / therapeutic use*
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors / administration & dosage
  • Growth Differentiation Factors / therapeutic use*
  • In Vitro Techniques
  • Mice
  • Osteoblasts / drug effects
  • Osteogenesis / drug effects*
  • Real-Time Polymerase Chain Reaction
  • Tissue Engineering / methods*


  • Drug Carriers
  • Fibrin Tissue Adhesive
  • GDF2 protein, human
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors