Brigitte Altmann1, Kerstin Rabel2, Ralf J Kohal3, Susanne Proksch4, Pascal Tomakidi5, Erik Adolfsson6, Falk Bernsmann7, Paola Palmero8, Tobias Fürderer9, Thorsten Steinberg5. 1. Department of Prosthetic Dentistry, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany; Department of Oral and Maxillofacial Surgery, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. Electronic address: Brigitte.altmann@uniklinik-freiburg.de. 2. Department of Prosthetic Dentistry, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany; Department of Oral Biotechnology, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. 3. Department of Prosthetic Dentistry, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. 4. Department of Operative Dentistry and Periodontology, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. 5. Department of Oral Biotechnology, University Medical Center Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany. 6. Swerea IVF AB, Argongatan 30, 43153 Mölndal, Sweden. 7. NTTF Coatings GmbH, Maarweg 30, 53619 Rheinbreitbach, Germany. 8. Department of Applied Science and Technology, INSTM R.U. PoliTO, LINCE Lab., Politecnico di Torino, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy. 9. MOESCHTER GROUP Holding GmbH & Co. KG, Hesslingsweg 65-67, 44309 Dortmund, Germany.
Abstract
OBJECTIVE: To adequately address clinically important issues such as osseointegration and soft tissue integration, we screened for the direct biological cell response by culturing human osteoblasts and gingival fibroblasts on novel zirconia-based dental implant biomaterials and subjecting them to transcriptional analysis. METHODS: Biomaterials used for osteoblasts involved micro-roughened surfaces made of a new type of ceria-stabilized zirconia composite with two different topographies, zirconium dioxide, and yttria-stabilized zirconia (control). For fibroblasts smooth ceria- and yttria-stabilized zirconia surface were used. The expression of 90 issue-relevant genes was determined on mRNA transcription level by real-time PCR Array technology after growth periods of 1 and 7 days. RESULTS: Generally, modulation of gene transcription exhibited a dual dependence, first by time and second by the biomaterial, whereas biomaterial-triggered changes were predominantly caused by the biomaterials' chemistry rather than surface topography. Per se, modulated genes assigned to regenerative tissue processes such as fracture healing and wound healing and in detail included colony stimulating factors (CSF2 and CSF3), growth factors, which regulate bone matrix properties (e.g. BMP3 and TGFB1), osteogenic BMPs (BMP2/4/6/7) and transcription factors (RUNX2 and SP7), matrix collagens and osteocalcin, laminins as well as integrin ß1 and MMP-2. SIGNIFICANCE: With respect to the biomaterials under study, the screening showed that a new zirconia-based composite stabilized with ceria may be promising to provide clinically desired periodontal tissue integration. Moreover, by detecting biomarkers modulated in a time- and/or biomaterial-dependent manner, we identified candidate genes for the targeted analysis of cell-implant bioresponse during biomaterial research and development.
OBJECTIVE: To adequately address clinically important issues such as osseointegration and soft tissue integration, we screened for the direct biological cell response by culturing human osteoblasts and gingival fibroblasts on novel zirconia-based dental implant biomaterials and subjecting them to transcriptional analysis. METHODS: Biomaterials used for osteoblasts involved micro-roughened surfaces made of a new type of ceria-stabilized zirconia composite with two different topographies, zirconium dioxide, and yttria-stabilized zirconia (control). For fibroblasts smooth ceria- and yttria-stabilized zirconia surface were used. The expression of 90 issue-relevant genes was determined on mRNA transcription level by real-time PCR Array technology after growth periods of 1 and 7 days. RESULTS: Generally, modulation of gene transcription exhibited a dual dependence, first by time and second by the biomaterial, whereas biomaterial-triggered changes were predominantly caused by the biomaterials' chemistry rather than surface topography. Per se, modulated genes assigned to regenerative tissue processes such as fracture healing and wound healing and in detail included colony stimulating factors (CSF2 and CSF3), growth factors, which regulate bone matrix properties (e.g. BMP3 and TGFB1), osteogenic BMPs (BMP2/4/6/7) and transcription factors (RUNX2 and SP7), matrix collagens and osteocalcin, laminins as well as integrin ß1 and MMP-2. SIGNIFICANCE: With respect to the biomaterials under study, the screening showed that a new zirconia-based composite stabilized with ceria may be promising to provide clinically desired periodontal tissue integration. Moreover, by detecting biomarkers modulated in a time- and/or biomaterial-dependent manner, we identified candidate genes for the targeted analysis of cell-implant bioresponse during biomaterial research and development.
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