Microstructural, mechanical, and osteocompatibility properties of Mg 2þ /F  -doped nanophase hydroxyapatite Zehra Pinar Sun, 1 Batur Ercan, 2 Zafer Evis, 1,3 Thomas J. Webster 2,4 1 Micro and Nanotechnology Program, Middle East Technical University, Ankara 06531, Turkey 2 Division of Engineering, Brown University, Providence, Rhode Island 02912 3 Department of Engineering Sciences, Middle East Technical University, Ankara 06531, Turkey 4 Department of Orthopaedics, Brown University, Providence, Rhode Island 02912 Received 22 July 2009; revised 29 October 2009; accepted 30 November 2009 Published online 24 March 2010 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.32745 Abstract: Pure as well as Mg 2þ - and F  -doped nanophase (i.e., grain sizes in the nanometer regime in at least one dimension) hydroxyapatite (HA) samples were synthesized by a precipitation method followed by sintering at 1100  C for 1 h to determine their microstructural, mechanical, and osteo- blast (bone-forming cell) adhesion properties pertinent for or- thopedic applications. Different amounts of Mg 2þ and F  ions (specifically from 0 to 7.5 mol %) were doped into the HA samples. X-ray diffraction was used to identify the presence of crystalline phases, lattice parameters, and crystal volumes of the samples. Fourier transform infrared (FTIR) was further used to chemically characterize HA, and thus FTIR patterns revealed the characteristic absorption bands of HA. Micro- hardness measurements were also performed to assess me- chanical properties of the novel formulations. Results of this study showed an improvement in sample density for some of the samples, which was a consequence of the molar per- centage variation of the dopants. Moreover, in most of the samples doped with Mg, b-tricalcium phosphate was observed as a second phase to HA. In addition, 1% Mg- and 2.5% F-doped HA had the highest microhardness values. Lastly, results demonstrated the highest osteoblast densities when the HA samples were doped with 2.5–7.5% Mg 2þ and F  . Thus, the results of this study suggest that decreasing the grain size of HA into the nanometer regime and doping HA with Mg 2þ and F  can potentially increase the efficacy of HA for orthopedic applications. V C 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 94A: 806–815, 2010 Key Words: hydroxyapatite, tricalcium phosphate, doping, sintering, l-hardness, X-ray diffraction, FTIR, osteoblast, nanotechnology INTRODUCTION Hydroxyapatite [HA, Ca 10 (PO 4 ) 6 (OH) 2 ] has been widely used as an implant material for orthopedic applications owing to its excellent biocompatibility properties resulting from its chemical similarity to the mineral portion of bone. 1–3 For example, HA has Ca and P elements in its hexagonal struc- ture and these elements are the same elements as those present in the inorganic part of bone. Nevertheless, poor mechanical properties (such as strength, hardness, and toughness) limit the use of HA in orthopedic load-bearing applications. 4 Therefore, HA has largely been used only in non-load bearing orthopedic applications (such as in ortho- pedic implant coatings and in ossicles in the middle ear 3,4 ). Because of the above, there have been many attempts to improve the properties of synthetic HA for orthopedic appli- cations. 5–10 Recently, improvements in the mechanical and biological properties of HA have been observed through the creation of nanophase (when compared with micron phase) crystalline HA. Bone possesses numerous nanometer crys- tals, therefore, research efforts on nanocrystalline HA have accelerated in recent years even showing greater in vivo osseointegration in rat calvaria when tantalum was coated with nanocrystalline compared to micron crystalline HA. 11 Moreover, improved properties of HA have been recently observed by doping HA with various elements. Biological HA crystals contain many ionic impurities such as: K þ , Mg 2þ , Na þ , CO 2 3 , and F  . 12–15 Substitution of these ions enhance biological, mechanical, and chemical properties of nanocrystalline HA. 14 Among numerous dopants added at 5 wt % to HA (Mg 2þ , Zn 2þ , La 3þ ,Y 3þ , In 3þ , and Bi 3þ ), Zn 2þ , In 3þ , and Bi 3þ have been reported as the most effective to- ward enhancing osteoblast (bone-forming cell) attachment. 14 Along this line, Mg 2þ is one of the most important biva- lent ions for maintaining bone health. Mg can substitute for Ca sites in the crystal structure of HA. In bone, Mg stimu- lates the transformation of immature (amorphic) bone into more crystalline, mature bone. The translocation of Mg into mineralized tissues prevents bone fractures by increasing the elastic properties of bone. 16,17 A lack of Mg in bone affects all stages of skeletal metabolism, causing cessation of bone growth, decreased osteoblastic and osteoclastic (bone- resorbing cells) activities, resulting in increased bone fragil- ity. Therefore, Mg incorporation into the HA structure is of great interest for developing artificial bone substitutes with improved properties. 18 Correspondence to: T. J. Webster; e-mail: thomas_webster@brown.edu Contract grant sponsor: Hermann Foundation 806 V C 2010 WILEY PERIODICALS, INC.