The combined mechanism of bone morphogenetic protein- and calcium phosphate-induced skeletal tissue formation by human periosteum derived cells
1 Tissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, O&N 1, Herestraat 49, bus 813, 3000 Leuven, Belgium.
2 Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1, Herestraat 49, bus 813, 3000 Leuven, Belgium.
3 Biomechanics Research Unit, University of Liege, Chemin des Chevreuils 1 – BAT 52/3, 4000 Liege 1, Belgium.
4 KU Leuven Campus Group T, Andreas Vesaliusstraat 13, 3000 Leuven, Belgium.
5 Department of Materials Engineering, KU Leuven, Kasteelpark Arenberg 44, bus 2450, 3001 Heverlee, Belgium.
Abstract
When combining osteogenic progenitor cells such as human periosteum derived cells (hPDCs) with osteoconductive biomaterials like calcium phosphate (CaP)-scaffolds,in vivobone 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 uponin vitro2D 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. Uponin vivoimplantation, 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, thein vitromechanism appears to predict thein vivooutcome. This study presents further evidence for the potential of BMP-technology in the development of clinically relevant cell-based constructs for bone regenerative strategies.
Keywords
- Bone tissue engineering
- bone morphogenetic proteins
- calcium phosphate
- progenitor cell
- cell signalling
- modelling
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