Engineering surfaces to direct integrin binding and signaling to promote osteoblast differentiation
Keselowsky, Benjamin George
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Cell adhesion to proteins adsorbed onto implanted surfaces is particularly important to host responses in biomedical and tissue engineering applications. Biomaterial surface properties influence the type, quantity and functional presentation (activity) of proteins adsorbed upon contact with physiological fluids, and modulate subsequent cell response. Cell adhesion to extracellular matrix proteins (e.g. fibronectin) is primarily mediated by the integrin family of cell-surface receptors. Integrins not only anchor cells, supporting cell spreading and migration, but also trigger signals that regulate survival, proliferation and differentiation. A fundamental understanding of the adhesive interactions at the biomaterial interface is critical to the rational design of biomaterial surfaces. Using model surfaces of self-assembled monolayers of alkanethiols on gold presenting well-defined surface chemistries (CH3, OH, COOH, NH2), we investigated the effects of surface chemistry on osteoblastic differentiation. We report that surface chemistry effectively modulates fibronectin adsorption, integrin binding, focal adhesion assembly and signaling to direct the osteoblast cellular functions of adhesion strength, gene expression and matrix mineralization. Specifically, surfaces presenting OH and NH2 functionalities provide enhanced functional presentation of adsorbed fibronectin, promoting specificity of integrin binding as well as elevating focal adhesion assembly and signaling. Furthermore, the OH and NH2 surfaces supported elevated levels of osteoblast differentiation as evidenced by osteoblast-specific gene expression and matrix mineralization. These results contribute to the development of design principles for the engineering of surfaces that direct cell adhesion for biomedical and tissue engineering applications. In particular, the understanding provided by this analysis may be useful in the engineering of surface properties for bone tissue repair and regeneration.