title: BMP2-coprecipitated calcium phosphate granules enhance osteoinductivity of deproteinized bovine bone, and bone formation during critical-sized bone defect healing.
abstract: Most materials used clinically for filling critical-sized bone defects (CSBD), such as deproteinized bovine bone (DBB), lack osteoinductivity so that their therapeutic effects are far from satisfactory. The effect of bone morphogenic protein 2 (BMP2)-coprecipitated biomimetic calcium phosphate granules (BMP2-cop.BioCaP) on osteoinduction of DBB graft(s) during CSBD healing is still unknown. We investigated whether BMP2-cop.BioCaP affects the osteoinductivity of DBB, bone formation, and foreign body reaction during CSBD healing. DBB + BMP2-cop.BioCaP, DBB, DBB + BMP2, DBB + BioCaP, and autologous bone grafts were implanted in the CSBD of sheep. Bone formation, DBB/BioCaP degradability, foreign body reaction, and osteoinductivity of DBB were analyzed histologically and histomorphometrically at week 4 and 8. Combination of BMP2-cop.BioCaP and DBB healed CSBD as effectively as autologous bone grafts. About 95% of the BMP2-cop.BioCaP had been degraded and replaced by new bone at week 8 in the DBB + BMP2-cop.BioCaP-group. Foreign body reaction was reduced in the DBB + BMP2-cop.BioCaP-group compared to the other groups. The independent use of the BMP2-cop.BioCaP did not achieve a satisfactory bone repair. In conclusion, the BMP2-cop.BioCaP showed good degradability and biocompatibility, and enhanced osteoinductivity of DBB during CSBD healing in sheep, suggesting BMP2-cop.BioCaP as a potential osteoinducer to enhance the therapeutic effects of the graft materials in clinic.
authors.affiliation: Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, the Netherlands.|Department of Oral Implantology, Hospital/School of Stomatology, Zhejiang University, Yan'an Road 395, 310006, Hangzhou, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Liu
authors.affiliation: School of Stomatology/Dental Clinic, Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, 310053, Hangzhou, China.
authors.forename: Yuanna
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, the Netherlands.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, the Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wismeijer
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, 300072, Tianjin, China.
authors.forename: Janak L
authors.initials: JL
authors.lastname: Pathak
authors.affiliation: Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, the Netherlands.
authors.forename: Yuelian
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001861:Bone Regeneration; D001842:Bone and Bones / Q000378:metabolism*; D002130:Calcium Phosphates / Q000378:metabolism*; D002417:Cattle; D003594:Cytoplasmic Granules / Q000378:metabolism*; D007150:Immunohistochemistry; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates