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Effect of different sustained bone morphogenetic protein‐2 release kinetics on bone formation in poly(propylene fumarate) scaffolds
Author(s) -
Olthof Maurits G. L.,
Kempen Diederik H. R.,
Herrick James L.,
Yaszemski Michael J.,
Dhert Wouter J. A.,
Lu Lichun
Publication year - 2018
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.33866
Subject(s) - plga , in vivo , glycolic acid , bone morphogenetic protein 2 , chemistry , kinetics , in vitro , biomedical engineering , biophysics , lactic acid , biochemistry , medicine , biology , genetics , physics , microbiology and biotechnology , quantum mechanics , bacteria
To investigate the effect of sustained bone morphogenetic protein‐2 ( BMP‐2) release kinetics on bone formation in poly(propylene fumarate) (PPF) scaffolds, different poly(lactic‐ co ‐glycolic acid) (PLGA) microspheres were used as delivery vehicles. All PPF scaffolds had the same 75% porous structure, while the degradation rate of the embedded PLGA microspheres was changed to tailor BMP‐2 release by varying the lactic‐to‐glycolic acid ( L:G ) ratio in the copolymer. Four PLGA microsphere formulations with 50/50, 65/35, 75/25, and 85/15 L:G ratios and varying in vivo degradation rates were fabricated. The in vitro and in vivo BMP‐2 release kinetics were determined by analyzing radiolabeled 125 I‐BMP‐2. Biological activity of released BMP‐2 was tested using a W20‐17 cell culture model in vitro and a subcutaneous rat model in vivo . Corresponding outcome parameters were defined as capacity to increase the in vitro AP activity in weekly consecutive cell cultures over 14 weeks and the in vivo bone formation after 7 and 14 weeks. The PLGA/PPF composites showed similar biological activity and BMP‐2 release profiles in vitro . In vivo , PPF/PLGA 85:15 composite released significantly less BMP‐2 per time point in the first weeks. Micro‐CT and histological analysis after 7 and 14 weeks of implantation showed bone formation, which significantly increased over time for all composites. No significant differences were seen between the composites. Overall, the results of this study show that small differences in BMP‐2 sustained release had no significant effect on BMP‐2 osteogenic efficacy in PPF/PLGA composites. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 477–487, 2018.