EARLY BONE FORMATION AT BONE BIOMATERIAL INTERFACE

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DESCRIPTION (Verbatim from the Applicant): The goal of this research is to gain a better understanding of the biological basis for successful orthopaedic and dental implant therapy by elucidating the early phenomena that govern osseointegration. In this proposal, the effect of sputtered hydroxyapatite (HA) crystallinity on early bone cell activity in vitro and in vivo will be investigated under highly controlled and defined conditions. Our overall hypothesis is that, under conditions where other variables are controlled, the degree of crystallinity of the HA surface directly affects early bone cell activity in vitro and the rate of development of osseointegration in vivo. The objective of this study is to correlate the effect of characterized HA crystallinity to dissolution and protein adsorption, bone cell response in vitro and early cell activities in vivo. In this proposal, Aim 1 will be to determine the relationship between crystalline content of well-characterized HA surfaces and 1) the adsorption of specific extracellular matrix proteins, fibronectin and osteopontin, and 2) the rate of dissolution of the surface. The HA and Ti coatings will be produced using sputter coating. The rationale for using the sputtering technology is due to the high coating-metal adhesion strength compared to plasma spraying. Protein adsorption and dissolution of the coatings will be measured over time. Aim 2 will determine the extent to which the crystalline content of HA surfaces effects osteoblast proliferation, differentiation, and metabolism in vitro. It is hypothesized in this aim that because osteoblast proliferation and differentiation may be affected by either the adsorption of specific extracellular matrix proteins, fibronectin and osteopontin, or the rate of dissolution of the surface, or both; metabolic activity leading to mineral formation will vary with the crystalline content of the HA surface. Implicit in this hypothesis is there exists an optimal crystalline content of an HA surface for the promotion of bone formation activity. Aim 3 will evaluate the extent to which the crystalline content of HA surfaces affects osseointegration in vivo. Early bone activity will be evaluated using histology, mechanical strength and immunohistochemistry in this aim. Data generated from this study will provide information on the early maturation of bone cells in the presence of implant biomaterials and will provide a correlation between biomaterial properties and bone cell responses in vitro and in vivo. Additionally, information generated will contribute to the development of an ideal implant surface, thereby reducing long-term implant failures.