Increased osteoblast adhesion on nanograined hydroxyapatite and tricalcium phosphate containing calcium titanate Celaletdin Ergun, 1 Huinan Liu, 2 John W. Halloran, 3 Thomas J. Webster 2 1 Mechanical Engineering Department, Istanbul Technical University, Taksim, 34437 Istanbul, Turkey 2 Division of Engineering, Brown University, Providence, Rhode Island 02912 3 Materials Science and Engineering, The University of Michigan, Ann Arbor, Michigan 48109 Received 19 March 2006; revised 1 May 2006; accepted 15 May 2006 Published online 21 November 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.30923 Abstract: Depending on the coating method utilized and subsequent heat treatments (such as through the use of plasma-spray deposition), inter-diffusion of atomic species across titanium (Ti) and hydroxyapatite (HA) coatings may result. These events may lead to structural and compo- sitional changes that consequently cause unanticipated HA phase transformations which may clearly influence the per- formance of an orthopedic implant. Thus, the objective of the present in vitro study was to compare the cytocompati- bility properties of chemistries that may form at the Ti:HA interface, specifically HA, tricalcium phosphate (TCP), HA doped with Ti, and those containing calcium titanate (CaTiO 3 ). In doing so, results of this study showed that osteoblast (bone-forming cells) adhesion increased with greater CaTiO 3 substitutions in either HA or TCP. Specifi- cally, osteoblast adhesion on HA and TCP composites with CaTiO 3 was almost 4.5 times higher than that over pure HA. Material characterization studies revealed that en- hanced osteoblast adhesion on these compacts may be due to increasing shrinkage in the unit lattice parameters and decreasing grain size. Although all CaTiO 3 composites ex- hibited excellent osteoblast adhesion results, Ca 9 HPO 4 (PO 4 ) 5 OH phase transformation into TCP/CaTiO 3 increased osteoblast adhesion the most; because of these reasons, these materials should be further studied for orthopedic applications. Ó 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A: 990–997, 2007 Key words: calcium phosphate; titanate; hydroxyapatite; osteoblasts; adhesion; orthopedic INTRODUCTION Mechanical properties are the principal limitation in the clinical use of hydroxyapatite (HA) as a bulk mate- rial in orthopedic load-bearing applications. Therefore, HA is commonly utilized as a coating material on tra- ditional metallic substrates in order to take advantage of their exceptional cytocompatibility properties coupled with the necessary mechanical properties of the under- lying metal. 1 Depending on the coating method utilized and sub- sequent heat treatments (such as through the use of plasma-spray deposition), interdiffusion of atomic species across the metal and HA coating may result. However, these events may lead to structural and compositional changes that consequently cause unan- ticipated HA phase transformations. Clearly, this new material formed at the metal/HA interface will have numerous consequences in terms of cytocompatibil- ity. For example, this unwanted material may cause toxic reactions in the body, decrease osteoblast (or bone-forming cells) adhesion, and/or alter the inter- facial bond strength with the underlying metal. 2 Previous research on titanium (Ti) and HA coatings revealed significant elemental Ti diffusion into the HA structure 3,4 ; specifically, calcium titanate (CaTiO 3 ) may be formed as a result of this atomic diffusion at the Ti:HA coating interface. 2,5 Importantly, it has been demonstrated that CaTiO 3 increases osteoblast adhe- sion compared to both pure HA and Ti and, thus, could possibly be beneficial if formed during the coat- ing process. The presence of CaTiO 3 (which is stable in an acidic environment) further decreases the disso- lution of HA in low pH conditions that may be created by osteoclast bone resorption or due to an inflamma- tory response. 6 In this manner, CaTiO 3 could increase the stability of bioactive HA on Ti. Further, significant apatite growth on CaTiO 3 in simulated body fluid (SBF) has been observed, thus, providing promise for Correspondence to: T.J. Webster; e-mail: Thomas_Webster@ Brown.edu Contract grant sponsor: Scientific & Technological Research Council of Turkey ' 2006 Wiley Periodicals, Inc.