Adsorption and Release of BMP-2 on Nanocrystalline Apatite-Coated and Uncoated Hydroxyapatite/b-Tricalcium Phosphate Porous Ceramics He ´ le ` ne Autefage, 1,5 Fabienne Briand-Me ´ sange, 2 Sophie Cazalbou, 1 Christophe Drouet, 1 Daniel Fourmy, 3 Ste ´ phane Gonc ¸ alve ` s, 4 Jean-Pierre Salles, 2 Christe ` le Combes, 1 Pascal Swider, 5 Christian Rey 1 1 Universite ´ de Toulouse, CIRIMAT, UPS-INPT-CNRS, ENSIACET, 31077 Toulouse Cedex 4, France 2 INSERM U563, Centre de physiopathologie de Toulouse Purpan, Dept. Lipoprote ´ ines et Me ´ diateurs Lipidiques, CHU Purpan, 31024 Toulouse Cedex 3, France 3 INSERM U858, Institut Louis Bugnard, 31432 Toulouse Cedex 4, France 4 Teknimed, Z.I. de Montredon, 31240 L’Union, France 5 Universite ´ de Toulouse, Biomechanics Laboratory EA3697, CHU Purpan, 31059 Toulouse Cedex, France Received 31 July 2008; revised 19 January 2009; accepted 15 April 2009 Published online 6 July 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.31447 Abstract: The association of bone morphogenetic proteins (BMPs) with calcium phosphate bioceramics is known to confer them osteoinductive properties. The aim of this study was to evaluate the surface properties, especially regarding recombinant human BMP-2 (rhBMP-2) adsorption and release, of commercial sintered biphasic calcium phosphate ceramics after coating with biomimetic nanocrystalline apatite. The raw and coated ceramics exhibited similar macroporous structures but different nanometer-sized pores contents. Both types of ceramics showed Langmuir-type adsorption isotherms of rhBMP-2. The coating noticeably increased the rate of adsorption and the total amount of growth factor taken up, but the maximum coverage per surface area unit as well as the affinity constant appeared lower for coated ceramics compared with raw ceramic surfaces. The limited advantage gained by coating the ceramics can be assigned to a lower accessibility of the surface adsorption sites compared with the raw ceramics. The quantity of rhBMP-2 spontaneously released in cell culture medium during the first weeks was lower for coated samples than for uncoated ceramics and represented a minor fraction of the total adsorbed amount. In conclusion, the nanocrystalline apatite coating was found to favor the adsorption of rhBMP-2 while providing a mean to fine tune the release of the growth factor. ' 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 91B: 706–715, 2009 Keywords: bone morphogenetic protein 2 (BMP-2); bioceramics; biphasic calcium phosphate (BCP); nanocrystalline apatite; protein adsorption and release INTRODUCTION One of the most efficient ways to improve the bone form- ing ability of biomaterials is their association with bone morphogenetic proteins (BMPs). Such growth factors, BMP-2 and BMP-7, the two most efficient variants of BMP growth factors available, have been associated with differ- ent types of biomaterials for orthopedic applications (col- lagen, calcium phosphate (Ca-P) cements, polymers, ceramics). 1 Although calcium phosphates are among the most frequently used biomaterials for bone reconstruction, little is known about their association with BMP. 2,3 Regarding porous ceramics, the growth factors are gener- ally associated with the implants by simple impregnation and drying and the type of bonding with the substrate and the release rate are often undetermined. 4–7 This lack of knowledge could explain divergences in the reported effect of such associations. Most studies testify to an improve- ment of bone formation with an acceleration of repair 4–7 ; however, a few studies have mentioned a resorptive process of bone attributed to a stimulation of osteoclast activity. 8,9 Recently, a few studies have been published on the adsorp- tion characteristics of BMP-2 on apatitic calcium phos- Correspondence to: H. Autefage (e-mail: autefag@cict.fr) Contract grant sponsor: Midi-Pyre ´ne ´es Region of France; Contract grant number: 06001852. Contract grant sponsor: Teknimed S.A. (L’Union, France) ' 2009 Wiley Periodicals, Inc. 706