Comparison of the Osteogenic Potential of Titanium- and Modified Zirconia-Based Bioceramics

Int. J. Mol. Sci. 2014, 15, 4442-4452; doi:10.3390/ijms15034442 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article Comparison of the Osteogenic Potential of Titanium and Modified Zirconia-Based Bioceramics Young-Dan Cho 1,2,†, Ji-Cheol Shin 1,†, Hye-Lee Kim 1, Myagmar Gerelmaa 1, Hyung-In Yoon 1, Hyun-Mo Ryoo 2, Dae-Joon Kim 3 and Jung-Suk Han 1,* 1 2 3 † Department of Prosthodontics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul 110-749, Korea; E-Mails: (Y.-D.C.); (J.-C.S.); (H.-L.K.); (M.G.); (H.-I.Y.) Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul 110-749, Korea; E-Mail: Department of Advanced Materials Engineering, Sejong University, Seoul 143-747, Korea; E-Mail: These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: or ; Tel.: +82-2-2072-2661; Fax: +82-2-2072-3860. Received: 28 January 2014; in revised form: 6 March 2014 / Accepted: 10 March 2014 / Published: 13 March 2014 Abstract: Zirconia is now favored over titanium for use in dental implant materials because of its superior aesthetic qualities. However, zirconia is susceptible to degradation at lower temperatures. In order to address this issue, we have developed modified zirconia implants that contain tantalum oxide or niobium oxide. Cells attached as efficiently to the zirconia implants as to titanium-based materials, irrespective of surface roughness. Cell proliferation on the polished surface was higher than that on the rough surfaces, but the converse was true for the osteogenic response. Cells on yttrium oxide (Y2O3)/tantalum oxide (Ta2O5)- and yttrium oxide (Y2O3)/niobium oxide (Nb2O5)-containing tetragonal zirconia polycrystals (TZP) discs ((Y, Ta)-TZP and (Y, Nb)-TZP, respectively) had a similar proliferative potential as those grown on anodized titanium. The osteogenic potential of MC3T3-E1 pre-osteoblast cells on (Y, Ta)-TZP and (Y, Nb)-TZP was similar to that of cells grown on rough-surface titanium. These data demonstrate that improved zirconia implants, which are resistant to temperature-induced Int. J. Mol. Sci. 2014, 15 4443 degradation, retain the desirable clinical properties of structural stability and support of an osteogenic response. Keywords: dental implant; titanium; zirconia; LTD; osteogenic potential 1. Introduction Several types of biomaterials have been used in dental implant studies; among them, titanium has been considered the most useful, as it has excellent mechanical properties and biocompatibility [1,2]. Modification of titanium surfaces via different additive (bioactive coatings) and subtractive processes (acid etching, grit-blasting) can improve osseointegration [3–10]. Additional trials showed that incorporation of titanium into glass-based biomaterials could enhance biological responses [11,12]. However, titanium’s metallic grayish color sometimes causes aesthetic problems in the anterior part of the dental implantation, as there is insufficient soft tissue to mask the peri-implant region. Furthermore, allergic reactions and sensitivities to titanium have been reported [13,14]. To minimize the soft tissue recession and aesthetic problems, many implant collars based on non-metallic materials have been developed. Tooth-colored and biocompatible ceramic materials or bioactive glass substrates are also potential candidates for novel implants [15]. Alumina is a highly biocompatible ceramic material with good aesthetic properties, but is associated with a high fracture risk. Because of this critical weakness, zirconia was introduced as a titanium alternative [16,17]. Zirconia exists in three phases, monoclinic (M), cubic (C) and tetragonal (T), depending on temperature. M-phase is fragile at room temperature, and therefore requires stabilization to prevent tetragonal (T)-to-monoclinic (M) phase transformation in technical applications [18,19]. A stress-induced transformation toughening mechanism improves the mechanical strength of zirconia, rendering it more suitable as a dental implant material [17,20]. Yttria (Y2O3) is used as a general stabilizer for maintaining the T-phase of ZrO2. Y2O3-stabilized tetragonal zirconia polycrystals (Y-TZP) have high strength, toughness, and biocompatibility, and elicit biological responses that are similar to those induced by titanium [21–23]. Therefore, Y-TZP is considered as a potential titanium alternative. However, zirconia exhibits structural instability upon low temperature degradation (LTD, often referred as “aging”), which is due to tetragonal (T)-to-monoclinic (M) phase transformation in moist or stress conditions [24]. Clearly, this limits the clinical utility of zirconia. Since the T-to-M transformation rate is most rapid at ~250 °C, it was not initially considered as a liability under physiological conditions of 37 °C [25,26]. However, several clinical failures in the use of hip prostheses were subsequently reported [25–29]. This spurred many efforts to inhibit LTD-dependent phase transformation, including addition of stabilizers such as niobium oxide (Nb2O5) [30,31] or tantalum oxide (Ta2O5) [32]. Unlike Y2O3, alloys of Ta2O5 or Nb2O5 contain lower numbers of cations coordinated to oxygen ions, and therefore increase the phase stability of T-ZrO2 [30,32]. Based on these observations, we developed 3Y-TZP co-doped with Nb2O5 and Ta2O5, (Y, Nb)-TZP, and (Y, Ta)-TZP. The purpose of the present study was to evaluate the capacity of these LTD-resistant (Y, Nb)-TZP and (Y, Ta)-TZP biomaterials to support osteogenesis, with a view to using them as replacements for current titanium-based dental implant materials. Int. J. Mol. Sci. 2014, 15 4444 2. Results and Discussion 2.1. Results 2.1.1. Surface Analysis of the Titanium and Zirconia Discs The average roughness values (Ra) of the specimens upon investigation with confocal laser microscopy are shown in Figure 1. The Ra values of Ti-m and Ti-a were 0.225 µm ± 0.03 (Figure 1A) and 0.633 µm ± 0.05 (Figure 1B), respectively. As previously reported, we increased surface roughness by modifying the surface using anodizing. The average roughness values of (Y, Nb)-TZP and (Y, Ta)-TZP were 0.092 µm ± 0.001 and 0.096 µm ± 0.001 (data not shown). To increase roughness, we sandblasted the zirconia with alumina spraying. Sandblasting with 50-µm alumina (Al2O3) at 1 bar pressure for 1 min created a rougher surface on the (Y, Ta)-TZP material when compared with (Y, Nb)-TZP (data not shown). To equalize the roughness, (Y, Nb)-TZP was instead subjected to 50 µm alumina (Al2O3) sandblasting with 2 bar for 1 min. This led to an Ra of 0.819 µm ±0.05 for (Y, Nb)-TZP (Figure 1C) and 0.880 µm ±0.06 for (Y, Ta)-TZP (Figure 1D). Figure 1. Three-dimensional confocal laser microscopy showing the roughness (Ra) of the examined substrate surfaces. (A) (...truncated)