The utility of implant materials in regeneration and repair of dento-alveolar bone relies on their strength, their biocompatibility, and their ability to facilitate normal differentiation of osteoblast precursors. Among the bone implant materials which have shown promise as bone bioactive substances are the calcium phosphate ceramics and glasses. At implantation, ceramic surfaces undergo dissolution, precipitation and ion exchange reactions which lead to a biologic apatitic surface on the implanted material. This reaction is accompanied by cellular activity leading to adsorption and incorporation of biological molecules and cell attachment. We hypothesize that modification of implants with a calcium-rich, or calcium-silicon-rich surface layer containing cell attachment proteins induces more effective osteogenesis. We further propose that there are both solution- mediated effects and cell surface changes which promote osteoblast differentiation on the implants. All these events, collectively, lead to the gradual incorporation of the ceramic- bone composite into adjacent bone. We will examine these hypotheses using multipotential bone marrow stromal cells (MSC) from rats and humans. These cells will differentiate on porous bioactive glass conditioned to generate a calcium phosphate-rich surface layer. In this project we focus on the two way interaction between the cells and the bioactive materials. We will focus on the mechanisms by which conditioned porous bioactive glasses are osteoinductive, and the possibility that other potentially useful implant materials can be modified to produce an osteoinductive surface similar to that found on conditioned bioactive glasses. We will 1) examine the hypothesis that integrin mediated cell-glass interactions promote osteogenesis; 2) analyze the osteogenic capacity of composites formed from poly (lactic-coglycolic acid) polymers plus glass- ceramic; and 3) test the hypothesis that solution-mediated factors derived from or concentrated in bioactive glass surfaces promote osteogenesis.
