Infections of the musculoskeletal system present a serious problem with regard to the field of orthopaedic and trauma medicine. The aim of the experiment described in this study was to develop a resorbable electrospun composite layer with the controlled elution of antibiotics to be used as bone/implant bioactive interface particularly in the case of known prosthetic joint infections or as a preventative procedure regarding primary joint replacement in a potentially infected site. The layer is composed of collagen, hydroxyapatite (HA) nanoparticles and Vancomycin hydrochloride (VAN). Three different compositions of the layers (0, 5 and 15wt% HA) and three preparation methods (lyophilisation, electrospinning, electrospinning and impregnation) are employed to prepare micro and nanostructured layers directly on the surface of titanium alloy implants. The study aimed principally to verify whether the local concentration of the active form of VAN released exceeded the minimum inhibitory concentration for VAN-resistant Staphylococcus aureus (VRSA >16mg/l) and to monitor the concentrations of VAN degradation products.