title: Induction of bone formation in biphasic calcium phosphate scaffolds by bone morphogenetic protein-2 and primary osteoblasts.
abstract: Bone tissue engineering strategies mainly depend on porous scaffold materials. In this study, novel biphasic calcium phosphate (BCP) matrices were generated by 3D-printing. High porosity was achieved by starch consolidation. This study aimed to characterise the porous BCP-scaffold properties and interactions of osteogenic cells and growth factors under in vivo conditions. Five differently treated constructs were implanted subcutaneously in syngeneic rats: plain BCP constructs (group A), constructs pre-treated with BMP-2 (group B; 1.6 µg BMP-2 per scaffold), seeded with primary osteoblasts (OB) (group C), seeded with OB and BMP-2 (group D) and constructs seeded with OB and pre-cultivated in a flow bioreactor for 6 weeks (group E). After 2, 4 and 6 weeks, specimens were explanted and subjected to histological and molecular biological analyses. Explanted scaffolds were invaded by fibrovascular tissue without significant foreign body reactions. Morphometric analysis demonstrated significantly increased bone formation in samples from group D (OB + BMP-2) compared to all other groups. Samples from groups B-E displayed significant mRNA expression of bone-specific genes after 6 weeks. Pre-cultivation in the flow bioreactor (group E) induced bone formation comparable with group B. In this study, differences in bone distribution between samples with BMP-2 or osteoblasts could be observed. In conclusion, combination of osteoblasts and BMP-2 synergistically enhanced bone formation in novel ceramic scaffolds. These results provide the basis for further experiments in orthotopic defect models with a focus on future applications in orthopaedic and reconstructive surgery.
authors: Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors: L A
authors: LA
authors: Strobel
authors: S N
authors: SN
authors: Rath
authors: A K
authors: AK
authors: Maier
authors: J P
authors: JP
authors: Beier
authors: A
authors: A
authors: Arkudas
authors: P
authors: P
authors: Greil
authors: R E
authors: RE
authors: Horch
authors: U
authors: U
authors: Kneser
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001842:Bone and Bones; D002130:Calcium Phosphates / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D006882:Hydroxyapatites / Q000737:chemistry*; D008297:Male; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D010477:Perfusion; D016062:Porosity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D006882:Hydroxyapatites; D012333:RNA, Messenger; C074950:hydroxyapatite-beta tricalcium phosphate; D017886:Durapatite; C020243:calcium phosphate