title: BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.
abstract: The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.
authors.affiliation: Department of Osteology, People's Hospital of Jiangxi Province, Nanchang, Jiangxi, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Osteology, People's Hospital of Jiangxi Province, Nanchang, Jiangxi, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zeng
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai, People's Republic of China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Yao
authors.affiliation: Department of Osteology, People's Hospital of Jiujiang County, Jiujiang, Jiangxi, People's Republic of China.
authors.forename: Qiquan
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Department of Osteology, People's Hospital of Jiangxi Province, Nanchang, Jiangxi, People's Republic of China.
authors.forename: Jingtang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Osteology, The Third Hospital of Nanchang City, Nanchang, Jiangxi, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Osteology, People's Hospital of Jiangxi Province, Nanchang, Jiangxi, People's Republic of China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D017886:Durapatite
keywords: bone graft; bone regeneration; synthetic bone substitutes