title: The combined mechanism of bone morphogenetic protein- and calcium phosphate-induced skeletal tissue formation by human periosteum derived cells.
abstract: When combining osteogenic progenitor cells such as human periosteum derived cells (hPDCs) with osteoconductive biomaterials like calcium phosphate (CaP)-scaffolds, in vivo bone formation can be achieved. This process is dependent on the early activation of Bone morphogenetic protein (BMP)-signalling. However, the bone forming process is slow and routinely only a limited amount of bone and bone marrow is formed. Therefore, we hypothesised that a robust clinically relevant outcome could be achieved by adding more physiological levels of potent BMP-ligands to these cell- and CaP-based constructs. For this, hPDCs were characterised for their responsiveness to BMP-ligands upon in vitro 2D stimulation. BMP-2, -4, -6 and -9 robustly induced osteochondrogenic differentiation. Subsequently, these ligands were coated onto clinically approved CaP-scaffolds, BioOss® and CopiOs®, followed by hPDC-seeding. Protein lysates and conditioned media were investigated for activation of BMP signalling pathways. Upon in vivo implantation, the most abundant bone formation was found in BMP-2 and BMP-6-coated scaffolds. Implanted cells actively contributed to the newly formed bone. Remnants of cartilage could be observed in BMP-coated CopiOs®-constructs. Computational analysis displayed that the type of BMP-ligand as well as the CaP-scaffold affects skeletal tissue formation, observed in a qualitative as well as quantitative manner. Furthermore, the in vitro mechanism appears to predict the in vivo outcome. This study presents further evidence for the potential of BMP-technology in the development of clinically relevant cell-based constructs for bone regenerative strategies.
authors.affiliation: Skeletal Biology and Engineering Research Center, O&N I Herestraat 49 - box 7003 13, 3000 Leuven, Belgium.frank.luyten@uz.kuleuven.ac.be.
authors.forename: J
authors.initials: J
authors.lastname: Bolander
authors.forename: W
authors.initials: W
authors.lastname: Ji
authors.forename: L
authors.initials: L
authors.lastname: Geris
authors.forename: V
authors.initials: V
authors.lastname: Bloemen
authors.forename: Y C
authors.initials: YC
authors.lastname: Chai
authors.forename: J
authors.initials: J
authors.lastname: Schrooten
authors.forename: F P
authors.initials: FP
authors.lastname: Luyten
mesh_terms: D001846:Bone Development / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001842:Bone and Bones / Q000378:metabolism*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002356:Cartilage / Q000254:growth & development; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019295:Computational Biology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D010521:Periosteum / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; C020243:calcium phosphate