Statement of Purpose: Although Titanium (Ti) and its alloys are biocompatible and non-toxic, once they are inserted in the body, as any biomaterial, they can triggers an inflammatory response, which usually is orchestrated by immune cells such macrophages and dendritic cells. In some scenarios, macrophages recognize Ti implant surface as a foreign body material expressing mainly M1 phenotype (considered classically activated or pro-inflammatory phenotype)1. These M1 macrophages protect the body and attack the implant trying to expulse or destroy it. However, the modification of the surface properties, and indeed, the introduction of nanofeatures, may help on the integration process. Several studied have described the role of nanotopography in macropahges bevahior, promoting the expresion of M2 phenotype (referred as alternative o anti-inlflammatory phenotype) which is related to regeneration process.2 Several surface treatments based on chemical or physical modification has been implemented to develop nanofeatures, however, the used of plasma has increased in the past decades. Here in this work we show an advanced plasma technology called Directed Irradiation synthesis (DIS) which combine energy and momentum deposition of Argon ions to induce self-organized patterns of heterogeneous nanostructures capable of enhancing the immune response of macrophages to M2 phenotype and at the same time increasing the bioactivity of the surface improving cell viability and adhesion of human cells.