In vitro evaluation of an injectable biphasic calcium phosphate (BCP) carrier system combined with recombinant human bone morphogenetic protein (rhBMP)-9

Article type: Research Article

Authors: Fujioka-Kobayashi, Masako^{a; b; *} | Schaller, Benoit^a | Zhang, Yufeng^c | Pippenger, Benjamin E.^d | Miron, Richard J.^e

Affiliations: [a] Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland | [b] Department of Oral Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan | [c] Department of Oral Implantology, University of Wuhan, Wuhan, China | [d] Institut Straumann AG, Basel, Switzerland | [e] Department of Periodontology, College of Dental Medicine, Nova Southeastern University, FL, USA

Correspondence: [*] Corresponding author: Masako Fujioka-Kobayashi, Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, CH-3010 Bern, Switzerland. E-mail: [email protected].

Abstract: Bone morphogenetic protein 9 (BMP9) has previously been characterized as the strongest osteoinductive growth factor among the BMP family. The aim of the present study was to evaluate the possibility of combining rhBMP9 with an injectable biphasic calcium phosphate (I-BCP, maxresorb inject®), since I-BCP is an easy to handle biomaterial with ideal properties for bone augmentation procedures. The adsorption potential of rhBMP9 as well as the cell behavior of bone stromal ST2 cells were investigated on cell viability, adhesion, proliferation and osteogenic differentiation for I-BCP combined with/without rhBMP9 in vitro. I-BCP demonstrated excellent adsorption/retention potential of rhBMP9 with a slow and steady release over a 10 day period by ELISA. Cell attachment at 8 hours and cell proliferation at 1, 3 and 5 days was decreased on I-BCP with/without rhBMP9 when compared to control tissue-culture plastic. While I-BCP had little influence on osteoblast differentiation, its combination with rhBMP9 significantly increased ALP activity at 7 days and mRNA levels of osteoblast differentiation markers including ALP and osteocalcin at 14 days. I-BCP served as an excellent carrier for rhBMP9 clearly demonstrating its osteoinductive potential. We therefore confirm the great potential of rhBMP9 to serve as a future regenerative growth factor for bone applications.

Keywords: Bone morphogenetic proteins, BMP9, BCP, biphasic calcium phosphate, carrier system, bone regeneration, bone augmentation, osteogenesis

DOI: 10.3233/BME-171675

Journal: Bio-Medical Materials and Engineering, vol. 28, no. 3, pp. 293-304, 2017