title: Effect of different sustained bone morphogenetic protein-2 release kinetics on bone formation in poly(propylene fumarate) scaffolds.
abstract: 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 radiolabeled125I-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.
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.|Department of Orthopedics, University Medical Center, 3508, GA, Utrecht, The Netherlands.|Faculty of Veterinary Medicine, Utrecht University, 3508, TD, Utrecht, The Netherlands.
authors.forename: Maurits G L
authors.initials: MGL
authors.lastname: Olthof
authors.affiliation: Department of Orthopaedic Surgery, Onze Lieve Vrouwe Gasthuis, 1090, HM, Amsterdam, The Netherlands.
authors.forename: Diederik H R
authors.initials: DHR
authors.lastname: Kempen
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.
authors.forename: James L
authors.initials: JL
authors.lastname: Herrick
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.affiliation: Department of Orthopedics, University Medical Center, 3508, GA, Utrecht, The Netherlands.|Faculty of Veterinary Medicine, Utrecht University, 3508, TD, Utrecht, The Netherlands.
authors.forename: Wouter J A
authors.initials: WJA
authors.lastname: Dhert
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905.
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D065546:Drug Liberation; D005121:Extremities / Q000637:transplantation; D005650:Fumarates / Q000737:chemistry / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008863:Microspheres; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer / Q000737:chemistry / Q000494:pharmacology; D011126:Polypropylenes / Q000737:chemistry / Q000494:pharmacology*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D005650:Fumarates; D007457:Iodine Radioisotopes; D011126:Polypropylenes; C097850:poly(propylene fumarate); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C000614960:Iodine-125
keywords: BMP-2 release kinetics; biomaterials; bone tissue engineering; poly(lactic-co-glycolic acid); poly(propylene fumarate)