Recombinant human bone morphogenetic protein-2 released from polyurethane-based scaffolds promotes early osteogenic differentiation of human mesenchymal stem cells.
The purposes of this study were to determine the pharmacokinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) from a polyurethane (PUR)-based porous scaffold and to determine the biological responses of human mesenchymal stem cells (hMSCs) to the rhBMP-2 released from those scaffolds. The rhBMP-2 was incorporated into the PUR three-dimensional (3D) porous scaffolds and release profiles were determined using enzyme-linked immunosorbent assay. The bioactivity of the rhBMP-2 containing releasates was determined using hMSCs and compared with exogenous rhBMP-2. Release of rhBMP-2 from PUR-based systems was bi-phasic and characterized by an initial burst followed by a sustained release for up to 21 days. Expression of alkaline phosphatase activity by hMSCs treated with the rhBMP-2 releasates was significantly greater than the cells alone (control) throughout the time periods. Furthermore, after 14 days of culture, the hMSCs cultured with rhBMP-2 releasate had a greater amount of mineralization compared to exogenous rhBMP-2. Overall, the rhBMP-2 release from the PUR-based scaffolds was sustained for 21 days and the releasates appeared to be bioactive and promoted earlier osteogenic differentiation and mineralization of hMSCs than the exogenous rhBMP-2.
Bone Tissue Engineering Center, Department of Biomedical Engineering and Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15219, USA.
Jinku
J
Kim
Jeffrey O
JO
Hollinger
D000328:Adult; D000469:Alkaline Phosphatase / Q000737:chemistry / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008648:Mesoderm / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D011140:Polyurethanes / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D011108:Polymers; D011140:Polyurethanes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000469:Alkaline Phosphatase