The objective of the biocompatibility core is to identify risks associate with the exposure of the biological tissues and cells to new resin based restorative materials and/or their components as they are developed. The biocompatibility core will utilize both in vitro and in vivo tests in order to characterize both the risks and hazards associated with the new resin based restorative materials.
In specific aim 1, initial testing for biocompatibility will be accomplished using in vitro culture methods employing mouse odontoblast and dental pulp cell lines, using survival as the end point parameter. Cell survival will be determined using the WST-1 and LDH assay systems. Assessment of both risk (bioactivity) and hazard (bioavailability) potential will be accomplished through indirect exposure of the cell monolayer to test substances. The goal of specific aim 1 is to identify component substances of newly developed resin based restorative materials that may be potential risks. An additional goal is the identification of new response parameters that may improve the correlation between in vitro evaluation and in vivo analysis. Thus, the expression of cytokines by human dental cell lines will be evaluated using commercial DNA hybridization arrays to develop custom dental specific arrays. Promoters for selected cytokine gene products will also be legated to a luciferase reporter gene and stably transfected into human dental cell lines to develop sensitive, and specific assays.
In specific aim 2, newly developed resin based restorative materials will be evaluated using in vivo assays, including stage one mutagenicity testing utilizing the Big Blue transgenic mouse system. Stage two tests evaluating mucous membrane irritation using the hamster cheek pouch and dermal sensitivity using the guinea pig will also be carried out. The goal of specific aim 2 is to evaluate the potential for in vivo toxicity of the material when in contact with the oral tissues, as well as to evaluate whether or not the new material is capable of producing an eczematous reaction.
In specific aim 3, the newly developed resin based restorative material will be examined using an in vivo usage test designed to evaluate the material exactly as it is intended to be used clinically. The goal of this aim is to evaluate the effects of the material on underlying dentin and pulp. The test will be accomplished using the ferret as the animal model system. This mammal has been shown to be a suitable model system for assessing the effects of dental procedures and materials on pulp and dentin.
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