title: The enhancement of osteogenesis by nano-fibrous scaffolds incorporating rhBMP-7 nanospheres.
abstract: It is advantageous to incorporate controlled growth factor delivery into tissue engineering strategies. The objective of this study was to develop a three-dimensional (3D) porous tissue engineering scaffold with the capability of controlled releasing recombinant human bone morphogenetic protein-7 (rhBMP-7) for enhancement of bone regeneration. RhBMP-7 was first encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanospheres (NS) with an average diameter of 300nm. Poly(l-lactic acid) (PLLA) scaffolds with interconnected macroporous and nano-fibrous architectures were prepared using a combined sugar sphere template leaching and phase separation technique. A post-seeding technique was then utilized to immobilize rhBMP-7 containing PLGA nanospheres onto prefabricated nano-fibrous PLLA scaffolds with well-maintained 3D structures. In vitro release kinetics indicated that nanosphere immobilized scaffold (NS-scaffold) could release rhBMP-7 in a temporally controlled manner, depending on the chemical and degradation properties of the NS which were immobilized onto the scaffold. In vivo, rhBMP-7 delivered from NS-scaffolds induced significant ectopic bone formation throughout the scaffold while passive adsorption of rhBMP-7 into the scaffold resulted in failure of bone induction due to either the loss of rhBMP-7 biological function or insufficient duration within the scaffold. We conclude that the interconnected macroporous architecture and the sustained, prolonged delivery of bioactive rhBMP-7 from NS immobilized nano-fibrous scaffolds actively induced new bone formation throughout the scaffold. The approach offers a new delivery method of BMPs and a novel scaffold design for bone regeneration.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2209, USA.
authors.forename: Guobao
authors.initials: G
authors.lastname: Wei
authors.forename: Qiming
authors.initials: Q
authors.lastname: Jin
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D043942:Nanotubes; D010012:Osteogenesis; D011994:Recombinant Proteins / Q000378:metabolism; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta