We will develop methods to explore cell response to tissue scaffolds that mimic natural bone through inclusion of a calcium phosphate phase. Calcium phosphate is the main component of the mineral phase of bone, and osteoblasts in vivo generate new bone in tight apposition to calcium phosphate implants. Polymeric scaffolds containing a calcium phosphate ceramic phase such as hydroxyapatite, tricalcium phosphates, amorphous calcium phosphate, or hydroxyapatite nanoparticles will be fabricated. Osteoblasts will be cultured in the scaffolds and the ability of the multiphase materials to support bone generation will be evaluated. Methods for fabricating scaffolds in the forms of arrays or gradients will be pursued to yield new methodologies for screening osteoblast performance in multiphase tissue scaffolds. Mechanisms of action will be explored including release of Ca and P ions, protein adsorption/conformation, changes in calcium phosphate crystallinity, and effects of surface chemistry and topology.