A major goal of restorative dentistry is the replacement of carious tooth structure with a material that most closely resembles the natural mineralized tissue, while at the same time preserving the vitality of the pulpo-dentinal complex. pal tissue exhibits an intrinsic defense mechanism against insult or injury which culminates in the differentiation of odontoblasts and the deposition of """"""""tertiary"""""""" dentin. Our goal is to develop a new dental material that when applied to the floor of a cavity will induce a predictable biologically favorable response resulting in tertiary dentin formation. We base our goal on the observations that the cytokine osteogenic protein 1(0P-I, BMP 7) is morphogenetic, inducing both proliferative and phenotypic changes in dental pulp cells. Our hypothesis is that a dental material containing OP-I when placed in the floor of a cavity preparation will evoke a predictable biological response of tertiary dentin formation within the dental pulp tissue. In order to test this hypothesis, we will pursue five Specific Aims. Specific #1 will identify the cell surface receptor(s) for OP-I and characterize their biological properties. Critical to this aim will be the characterization of the receptors for these cytokines within odontoblast and dental pulp cell populations.
Specific Aim #2 will determine the optimal conditions for the inductive effect of OP-I in vitro on stimulation of dentin extracellular matrix production and the cytodifferentiation of dental pulp cells into functional odontoblasts. Determination of the dosage parameters for in vivo studies will be facilitated by the availability of an unique monolayer cell culture system as well as immortalized dental pulp and odontoblast cell lines which have been established in our laboratory.
Specific Aim #3 will determine the parameters of convective and diffusive transdentinal movement of 0P-1 in vitro.
This aim will estimate the concentration of cytokine needed at the surface, in order to deliver the proper dose established in the Specific Aim #1.
In Specific Aim #4, we will develop gel or solution delivery system which incorporates 0P-1 in an active form for transport to the floor of a cavity preparation, which will not interfere with the bonding of subsequently applied restorative materials. We will focus our investigation on delivery systems with a short-term release. Our last Specific Aim #5 will determine the effects of the dentin-inductive OP-I restorative liner on dental pulp tissue in vivo. This will accomplished by measuring the in vivo migration of cytokine(s) transdentinally and determination of the mitogenic effects of these molecules. It is our expectation that the transdentinal induction of tertiary dentin will become an integral part of the restorative dental armentarium through the proper fusion of basic cellular and molecular biology and dental materials.
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