Bioactive glasses and ceramics have emerged as promising substrates for bone tissue engineering. These materials react with physiological fluids, enhance bone formation, and bond to bone. Bioactivity involves physicochemical surface reactions and cell-mediated events, including cell adhesion to adsorbed extracellular matrix proteins. In this study, the effects of fibronectin adsorption and surface physicochemistry on osteoblast-like cell adhesion to bioactive glass, stoichiometric hydroxyapatite, and nonreactive glass were investigated. The bioactive glass substrates were pretreated in a simulated physiological solution to produce three reaction layers: unreacted glass, amorphous calcium-phosphate, and carbonated hydroxyapatite. Based on a numerical analysis that predicted differences in mechanical and chemical conditions at the bioactive interface, a spinning disk device was used to quantify cell adhesion. This device applied a linear range of forces to attached cells while maintaining constant and uniform chemical conditions at the surface. The number of adherent cells decreased sigmoidally with applied force and the resulting detachment profile provided measurements of adhesion strength. For the same amount of adsorbed fibronectin, cell adhesion was higher on surface reacted bioactive glasses than on unreacted bioactive glass, non-reactive glass. and stoichiometric hydroxyapatite. Furthermore, cell adhesion strength increased linearly with fibronectin surface density. Analysis of this fundamental relationship revealed that improved adhesion to reacted bioactive glasses resulted from enhanced cell receptorfibronectin interactions, suggesting substrate-dependent conformational changes in the adsorbed fibronectin. Enhanced cell adhesion to reacted bioactive glasses correlates with improved cellular function in vitro and suggests that bioactivity for these substrates results from the formation of a calcium-phosphate rich layer that interacts with specific proteins. Surface modification to enhance the biological activity of adsorbed proteins followed by specific protein adsorption is a powerful method to tailor substrates for celland tissue-specific applications.