title: Growth factor delivery of BMP9 using a novel natural bovine bone graft with integrated atelo-collagen type I: Biosynthesis, characterization, and cell behavior.
abstract: Within the past years, BMP9 has been characterized as one of the most osteogenic bone-inducers among the BMP family, however up until recently, BMP9 has only been available through adenovirus transfection experiments (gene therapy) not approved for clinical use. The aim of this study was to investigate recombinant rhBMP9 versus rhBMP2 at 2 concentrations (10 and 100 ng/mL) in combination with 2 bone grafts: (1) a natural bone mineral (NBM) without collagen versus (2) a novel NBM integrated with atelo-collagen type I (NBM-Col). Scanning electron microscopy revealed that while NBM demonstrated a mineralized roughened surface morphology, NBM-Col particles contained many more visible collagen fibrils throughout the scaffold surface significantly increasing rhBMP adsorption from 8 h to 10 days (as quantified by ELISA). Thereafter, ST2 preosteoblasts were used to investigate cell attachment, proliferation, and differentiation. While little change was observed for cell attachment/proliferation, osteoblast differentiation demonstrated a significant increase in alkaline phosphatase (ALP) activity when scaffolds were loaded with rhBMP9 when compared to rhBMP2. Furthermore, a 2-3 fold increase in alizarin red staining, and in mRNA levels of osteoblast differentiation markers Runx2, Collagen1α2, ALP, and osteocalcin was observed when rhBMP9 was combined with NBM-Col when compared to NBM without collagen at equivalent doses and when compared to rhBMP2. The results from this study demonstrate that (1) the use of rhBMP9 significantly and markedly induced osteoblast differentiation when compared to rhBMP2 and (2) the incorporation of atelo-collagen type I into NBM bone grafts markedly improved these findings by serving as a scaffold capable of improving growth factor adsorption and osteoblast behavior. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 408-418, 2017.
authors.affiliation: Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida.|Department of Cranio-Maxillofacial Surgery, Bern University Hospital, Inselspital, Switzerland.|Department of Oral Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Fujioka-Kobayashi
authors.affiliation: Department of Cranio-Maxillofacial Surgery, Bern University Hospital, Inselspital, Switzerland.
authors.forename: Benoit
authors.identifier: 0000-0002-6861-2340
authors.initials: B
authors.lastname: Schaller
authors.affiliation: Department of Cranio-Maxillofacial Surgery, Bern University Hospital, Inselspital, Switzerland.
authors.forename: Nikola
authors.initials: N
authors.lastname: Saulacic
authors.affiliation: Department of Oral Implantology, University of Wuhan, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miron
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D001842:Bone and Bones / Q000737:chemistry*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003094:Collagen / Q000737:chemistry*; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D016503:Drug Delivery Systems / Q000379:methods*; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis
chemical_list: D000943:Antigens, Differentiation; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C000601279:COL1A2 protein, human; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; C493709:RUNX2 protein, human; C059821:atelocollagen; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase
keywords: BMP; BMP2; BMP9; atelocollagen; bone graft; bone induction; bone regeneration bone formation; collagen; growth factor; natural bone mineral; osteogenesis; osteoinduction