TY - JOUR AB - OBJECTIVE: Titanium (Ti)- and Zirconia (ZrO2)-implants in mini pig maxillae were compared with respect to Ti/zirconium (Zr) release into the surrounding bone tissues, the resulting short term tissue responses and the potential toxicity. METHODS: Ti/Zr release from Ti- and ZrO2-implants in mini pig maxillae was determined with inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). The spatial distribution of Ti and Zr in maxilla tissues near the implant surface was assessed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). A histological analysis was performed to investigate the tissue responses after 12 weeks of implantation. The cytotoxicity and DNA damage of Ti particles and ZrO2 particles were studied with XTT and Comet assay. RESULTS: The mean Ti content in the bone adjacent to Ti-implants was 1.67 mg/kg-bone weight. The highest Ti content detected was 2.17 mg/kg-bone weight. The mean Zr content in the bone adjected to ZrO2-implants was 0.59 mg/kg-bone weight. The highest Zr content was 0.75 mg/kg-bone weight. The spatial distribution of the Ti and Zr in bone showed mainly a higher intensity of Ti and Zr close to the screw thread outer tip rather. Histological analysis indicated that near both implant-types signs of bone marrow fibrosis were present. EC50 of commercially available ZrO2-nanoparticles (NPs, <100 nm) and ZrO2-microparticles (MPs, <5 μm) was 13.96 mg/ml and 80.99 mg/ml, respectively. ZrO2-NPs and ZrO2-MPs can induce DNA damage at 70 μg/ml and 810 μg/ml, respectively. SIGNIFICANCE: After 12-weeks of implantation, increased concentrations of Ti and Zr can be detected in bone/tissues near Ti- and ZrO2-implants in mini pig maxillae. Ti content released from Ti-implants is two times higher than the Zr content released from ZrO2-implants. ZrO2-NPs showed lower cytotoxicity and DNA damage compared to results reported for Ti-NPs in human cells. AU - He, X.* AU - Reichl, F.X.* AU - Milz, S.* AU - Michalke, B. AU - Wu, X. AU - Sprecher, C.M.* AU - Yang, Y.* AU - Gahlert, M.* AU - Röhling, S.* AU - Kniha, H.* AU - Hickel, R.* AU - Högg, C.* C1 - 58732 C2 - 48265 SP - 402-412 TI - Titanium and zirconium release from titanium- and zirconia implants in mini pig maxillae and their toxicity in vitro. JO - Dent. Mater. VL - 36 IS - 3 PY - 2020 SN - 0109-5641 ER - TY - JOUR AB - Objective. To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.Methods. Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing. Cells were cultured with previously washed and unwashed membranes (n=4) and in the medium used for washing (eluate). Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit. Growth factor content of the membranes was measured using multiplex ELISA.Results. The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects. The highest impact was observed for DM, its eluate doubled the cell proliferation of adherent cells when compared to the control (p<0.001). The eluate of OG did not influence eluate cell cultures (p>0.05). The presence of membranes had different impact on hMSCs and PDLs. hMSCs seem to be more resistant to the inhibitory effects of BG, OG and BM. hMSCs are only affected by OX, which actually stimulates hMSCs when the specimens are not washed previously. PDLs however proliferate significantly less once they are placed into culture with BM and OG as well as BG-not washed. Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome. The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001). Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml. Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.Significance. The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests. The findings may be due to various factors, especially differences observed in composition, processing and bFGF content. (C) 2019 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved. AU - Spinell, T.* AU - Saliter, J.* AU - Hackl, B.* AU - Unger, K. AU - Hickel, R.* AU - Folwaczny, M.* C1 - 55986 C2 - 46687 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 963-969 TI - In-vitro cytocompatibility and growth factor content of GBR/GTR membranes. JO - Dent. Mater. VL - 35 IS - 7 PB - Elsevier Sci Ltd PY - 2019 SN - 0109-5641 ER - TY - JOUR AB - OBJECTIVE: The aim of this study was to measure titanium (Ti) content in human jawbones and to show that Ti was released from dental implants inserted into these jawbones. METHODS: Seven samples from four human subjects with dental implants were analysed as test group and six bone samples of similar topographical regions from six human subjects without implants served as control. The contents of various elements in human jawbones were detected by inductively coupled plasma optical emission spectrometry. The distributions of various isotopes in human mandibular bone were measured with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Histological analyses of undecalcified, Giemsa-Eosin stained mandible sections were performed by light microscopy and particles were identified in human bone marrow by scanning electron microscope-energy dispersive X-ray analysis. RESULTS: In test group only Ti content was significantly higher compared to control group. The mean contents of Ti were 1940μg/kg in test group and 634μg/kg in control group. The highest Ti content detected in human mandibular bone was 37,700μg/kg-bone weight. In samples 4-7 (human subjects II-IV), increased Ti intensity was also detected by LA-ICP-MS in human mandibular tissues at a distance of 556-1587μm from implants, and the intensity increased with decreasing distance from implants. Particles with sizes of 0.5-40μm were found in human jawbone marrow tissues at distances of 60-700μm from implants in samples 4-7. SIGNIFICANCE: Ti released from dental implants can be detected in human mandibular bone and bone marrow tissues, and the distribution of Ti in human bone was related to the distance to the implant. AU - He, X.* AU - Reichl, F.X.* AU - Wang, Y.* AU - Michalke, B. AU - Milz, S.* AU - Yang, Y.* AU - Stolper, P.* AU - Lindemaier, G.* AU - Graw, M.* AU - Hickel, R.* AU - Högg, C.H.* C1 - 48815 C2 - 41433 SP - 1042-1051 TI - Analysis of titanium and other metals in human jawbones with dental implants - a case series study. JO - Dent. Mater. VL - 32 IS - 8 PY - 2016 SN - 0109-5641 ER - TY - JOUR AB - Introduction: Titanium (Ti) and its alloys are used for implants and other dental materials. In this study, cytotoxicity, DNA damage, cellular uptake and size of three kinds of Ti particles were measured. Methods: Cytotoxicity for Ti microparticles (Ti-MPs, <44. μm), NiTi microparticles (NiTi-MPs, <44. μm), and Ti nanoparticles (Ti-NPs, <100. nm) in periodontal ligament (PDL)-hTERT cells was measured with XTT test. DNA damage was determined with comet assay. Particle size was measured with scanning electron microscope, intracellular uptake was determined with laser scanning confocal microscopy and transmission electron microscopy. Results: The EC50 values of investigated particles were: 2.8mg/ml (Ti-NPs), 41.8mg/ml (NiTi-MPs) and >999mg/ml (Ti-MPs). The Olive Tail Moment (OTM) values at 1/10 EC50 were: 3.2 (Ti-NPs) and 2.2 (NiTi-MPs). An OTM of 2.2 for Ti-MPs was detected at the concentration of 6666μg/ml. Determined sizes of investigated particles were 20-250nm (Ti-NPs), 0.7-90μm (NiTi-MPs) and 0.3-43μm (Ti-MPs). The highest cellular uptake efficiency was observed with Ti-NPs, followed by Ti-MPs and NiTi-MPs. Only Ti-NPs were found in the nucleus. Conclusion: Compared to Ti-MPs and NiTi-MPs, Ti-NPs induced higher cellular uptake efficiency and higher toxic potential in PDL-hTERT cells. Ni in the alloy NiTi induced an increase in the toxic potential compared to Ti-MPs. AU - He, X.* AU - Hartlieb, E.* AU - Rothmund, L.* AU - Waschke, J.* AU - Wu, X. AU - van Landuyt, K.L.* AU - Milz, S.* AU - Michalke, B. AU - Hickel, R.* AU - Reichl, F.X.* AU - Högg, C.H.* C1 - 44484 C2 - 36931 CY - Oxford SP - 734-744 TI - Intracellular uptake and toxicity of three different Titanium particles. JO - Dent. Mater. VL - 31 IS - 6 PB - Elsevier Sci Ltd PY - 2015 SN - 0109-5641 ER - TY - JOUR AB - Objectives. Methacrylate-based (co)monomers released from dental composites can be, metabolized in vivo to methacrylic acid (MA). MA can be further oxidized to the toxic 2,3-epoxymethacrylic acid (2,3-EMA) by cytochrome P450 (CYP450) enzymes. The subform CYP450-2E1, can metabolize xenobiotics with low-molecular weight to epoxides. Oral cells are highly exposed to (co) monomers released from composites. Therefore in this study the, expression of CYP450-2E1 in human oral (and other) cells was investigated as well as the formation of 2,3-EMA in cells exposed to MA. Methods. Following human oral cells were used: human gingiva fibroblasts (HGF), human pulp fibroblasts (HPF), and human tumor buccal keratinocytes (SqCC/Y1). As negative control V79 cells without CYP450-2E1 expression were used. As positive controls V79 cells with CYP450-2E1 expression (V79-CYP450-2E1) and pooled human liver microsomes were used. The expression of CYP450-2E1 in cells was analyzed with the real-time polymerase chain reaction (RT-PCR). 2,3-EMA was quantified by the use of the method of gas chromatography/mass spectrometry (GC/MS). Results. The highest expression of CYP450-2E1 was found in human liver microsomes, followed by SqCC/Y1 cells, V79-CYP450-2E1 cells, HGF, and HPF. The highest amount of 2,3-EMA (mu mol/L; mean +/- SEM, n = 3) was found in human liver microsomes (5.0 +/- 1.0), followed by SqCC/Y1 cells (2.5 +/- 0.8), V79-CYP450-2E1 cells (1.5 +/- 0.6), HPF (0.3 +/- 0.3), and HGF (0.2 +/- 0.2). Significance. It is concluded that the formation of the toxic epoxide 2,3-EMA, as intermediate in the metabolism of dental materials, can occur also in human oral cells which can express the CYP450-2E1 enzyme system. AU - Reichl, F.X.* AU - Seiss, M.* AU - Buters, J. AU - Behrendt, H. AU - Hickel, R.* AU - Durner, J. C1 - 5688 C2 - 28001 CY - Oxford SP - 1151-1156 TI - Expression of CYP450-2E1 and formation of 2,3-epoxymethacrylic acid (2,3-EMA) in human oral cells exposed to dental materials. JO - Dent. Mater. VL - 26 IS - 12 PB - Elsevier Sci. Ltd. PY - 2010 SN - 0109-5641 ER -