Changes of a material biointerface allow for specialized cell signaling and diverse biological responses. Biomaterials incorporating immobilized bioactive ligands have been widely introduced and used for tissue engineering and regenerative medicine applications in order to develop biomaterials with improved functionality. Furthermore, a variety of physical and chemical techniques have been utilized to improve biomaterial functionality, particularly at the material interface. At the interface level, the interactions between materials and cells are described. The importance of surface features in cell function is then examined, with new strategies for surface modification being highlighted in detail.