Insufficient integration with local host tissues is a significant problem that adversely affects the performance of implanted biomedical devices. Poor tissue integration leaves patients susceptible to complications associated with adverse foreign body reactions and infections that typically mandate expensive and elevated-risk revision surgery. The aging population and growing incidence of medical implants makes the development of bio-functional implant surfaces a high priority research imperative. Here multifunctional surfaces are reported that are capable of regulating cell adhesion and triggering cell differentiation to facilitate osseointegration of implantable devices. The approach described is universal, cost- and time-effective. It relies on a unique combination of two advances: i) a reactive interface provided by a plasma activated coating (PAC) that covalently immobilises bioactive molecules with significantly higher efficiency than conventional technologies, and ii) multifunctional molecules (bi-functional fusion-proteins) that regulate multiple cellular responses. Covalent linking of the molecules, their high density, and desired orientation are demonstrated. The effectiveness of these functional interfaces to regulate mesenchymal stem cell attachment and differentiation is confirmed suggesting the ability to regulate osseointegration. This method is a leap forward in the fabrication of truly biofunctional materials tailored for particular applications.