The establishment and maintenance of functional endothelial cells (ECs) on an engineered surface is central to tissue engineering. As the field advances, the role of cellular mechanisms, particularly the adhesive interaction between the surface of implantable devices and biological systems, becomes more relevant in both research and clinical practice. Knowledge of these interactions can address many fundamental biological questions and would provide key design parameters for medical implants. It has been shown that EC functionality and adhesivity, crucial for the re-endothelialization process, can be induced by nanotopographical modification. Therefore, the goal of this dissertation research was to develop an ensemble surface composing of nanoscale features for the enhancement of endothelial cell adhesion. Without adhesion, subsequent vital mechanism involved in cell alignment, elongation or spreading, proliferation, migration, and ECM proteins deposition will not occur.Experiments in support of this goal were broken down into three specific aims. The first aim was to characterize and develop a size-dependent self-assembly (SDSA) nanoarray of Octamer transcription factor 4 as a demonstration to the fabrication of nanoscale feature surface. This nanoparticle array platform was a pilot studied for the second aim, which was the development of an ensemble surface of nanoscale features for endothelial cell adhesion. The third aim was to evaluate and assess EC response to the ensemble surface.Hence, we developed an ensemble surface composed of nanoscale features and adhesive elements for EC adhesivity. By using shear stress as a detachment force, we demonstrated greater cell retention by the ensemble surface than uniform controls. Adhesive interactions and cellular migration through integrin expressions, which are critical to tissue development and wound healing process was also observed. Furthermore, cell viability was relatively sustainable, as indicated by the low expression of apoptotic signaling molecules. The findings presented within this dissertation research can be applicable to blood-contact medical implants and possess the potential for future clinical translation.