Franziska Ehlicke1, Jonathan Berndt2, Nina Marichikj3, Doris Steinmüller-Nethl4, Heike Walles5, Ernst-Ulrich Berndt6, Jan Hansmann7. 1. University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, Roentgenring 11, 97070 Wuerzburg, Germany. Electronic address: franziska.ehlicke@uni-wuerzburg.de. 2. Natural Dental Implants AG, Edisonstrasse 63, 12459 Berlin, Germany. Electronic address: jonathan.berndt@gmx.de. 3. University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, Roentgenring 11, 97070 Wuerzburg, Germany. Electronic address: nina.maricik@gmail.com. 4. DiaCoating GmbH, c/o Werkstätte Wattens, Weisstrasse 9, 6112 Wattens, Austria. Electronic address: doris.steinmueller@diacoating.com. 5. University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, Roentgenring 11, 97070 Wuerzburg, Germany; Fraunhofer Institute for Silicate Research ISC, Translational Center Regenerative Therapies, Roentgenring 11, 97070 Wuerzburg, Germany. Electronic address: heike.walles@isc.fraunhofer.de. 6. Natural Dental Implants AG, Edisonstrasse 63, 12459 Berlin, Germany. Electronic address: ernst-ulrich.berndt@t-online.de. 7. University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, Roentgenring 11, 97070 Wuerzburg, Germany; Fraunhofer Institute for Silicate Research ISC, Translational Center Regenerative Therapies, Roentgenring 11, 97070 Wuerzburg, Germany. Electronic address: jan.hansmann@isc.fraunhofer.de.
Abstract
OBJECTIVES: Before application in dental practice, novel dental materials are tested in vitro and in vivo to ensure safety and functionality. However, transferability between preclinical and clinical results is often limited. To increase the predictive power of preclinical testing, a biomimetic in vitro test system that mimics the wound niche after implantation was developed. METHODS: First, predetermined implant materials were treated with human blood plasma, M2 macrophages and bone marrow stromal stem cells. Thereby, the three-dimensional wound niche was simulated. Samples were cultured for 28 days, and subsequently analyzed for metabolic activity and biomineralization. Second test level involved a cell-infiltrated bone substitute material for an osseointegration assay to measure mechanical bonding between dental material and bone. Standard and novel dental materials validated the developed test approach. RESULTS: The developed test system for dental implant materials allowed quantification of biomineralization on implant surface and assessment of the functional stability of mineralized biomaterial-tissue interface. Human blood plasma, M2 macrophages and bone marrow stromal stem cells proved to be crucial components for predictive assessment of implant materials in vitro. Biocompatibility was demonstrated for all tested materials, whereas the degree of deposited mineralized extracellular matrix and mechanical stability differed between the tested materials. Highest amount of functional biomineralization was determined to be on carbon-coated implant surface. SIGNIFICANCE: As an ethical alternative to animal testing, the established in vitro dental test system provides an economic and mid-throughput evaluation of novel dental implant materials or modifications thereof, by applying two successive readout levels: biomineralization and osseointegration.
OBJECTIVES: Before application in dental practice, novel dental materials are tested in vitro and in vivo to ensure safety and functionality. However, transferability between preclinical and clinical results is often limited. To increase the predictive power of preclinical testing, a biomimetic in vitro test system that mimics the wound niche after implantation was developed. METHODS: First, predetermined implant materials were treated with human blood plasma, M2 macrophages and bone marrow stromal stem cells. Thereby, the three-dimensional wound niche was simulated. Samples were cultured for 28 days, and subsequently analyzed for metabolic activity and biomineralization. Second test level involved a cell-infiltrated bone substitute material for an osseointegration assay to measure mechanical bonding between dental material and bone. Standard and novel dental materials validated the developed test approach. RESULTS: The developed test system for dental implant materials allowed quantification of biomineralization on implant surface and assessment of the functional stability of mineralized biomaterial-tissue interface. Human blood plasma, M2 macrophages and bone marrow stromal stem cells proved to be crucial components for predictive assessment of implant materials in vitro. Biocompatibility was demonstrated for all tested materials, whereas the degree of deposited mineralized extracellular matrix and mechanical stability differed between the tested materials. Highest amount of functional biomineralization was determined to be on carbon-coated implant surface. SIGNIFICANCE: As an ethical alternative to animal testing, the established in vitro dental test system provides an economic and mid-throughput evaluation of novel dental implant materials or modifications thereof, by applying two successive readout levels: biomineralization and osseointegration.