## 1 Introduction  
Besides composition, topography represents another key factor in research aimed at categorizing and influencing the hierarchical organization of cells into distinct tissue [1]. Studies showed that topography plays a crucial role in initiating processes required for inducing and maintaining a specific cellular response or tissue-related activities, for instance. Specifically, recent trends in tissue engineering technologies [2] have focused on understanding such organization and how could it be designed to instill both nano to macroscale functionality when cell adhesion and orientation are considered [3; 4; 5]. For instance, various studies have evaluated both specific topography and cell functionality for understanding cellular activity towards a desired response, with most of these studies using macrophages, osteoblasts, mesenchymal stem cells (MSCs), and fibroblasts, etc. [6; 7; 8]. In other analyses, topographic organization has been used to modulate the phenotype of osteoblasts [9] and fibroblasts [10; 11]. More recently, additional reports evaluated how surface topography affects epithelial tissue functionality [12; 13; 14; 15]. The additional focus on epithelial cells was motivated by several factors including their known roles in maintaining the integrity and functionality of a tissue to be translated to artificial tissue [16] formation, their demonstrated abilities to create biochemical gradients to help guide cell positioning into a specific location [17] or potential to serve as a model system for stem cells' analysis [18; 19]. Immortalized human bronchial epithelial cells (BEAS-2B), for instance, are now established as non-tumorigenic epithelial cell lines from human bronchial epithelium and are used as an in vitro cell model for respiratory diseases studies [20] or more recently, as a model for human umbilical cord-derived MSCs cell lines [18; 19]. Cell-specific expression profiles of surface markers, the exhibition of similar osteogenic and adipogenic differentiation potential and suppressive activities on proliferation of mitogen-activated total T lymphocytes, but not on type 2 macrophage polarization, have been shown to be extremely beneficial when implementing these cells in artificial tissue function design and structural functionality. More recent studies showed how using topography with restrictive effects could impact epithelial organoids formation, with such analysis also describing the roles of surface topographies in inducing rapid epithelial polarization and tissue organization [21; 22]. For instance, a wire-like topography induced localized restrictive effects on cell spreading [23; 24], with cultured human airway epithelial cells (Calu-3) and Madin-Darby canine kidney cells (MDCK-II) forming organoids that closely resembled in vivo morphologies [25]. Notably, in such studies and despite research imposing distinct geometries and mechanical restrictions to cell spreading, the possible effects of high and low densities packed micro topographies have not been fully investigated. Future developments in tissue engineering design and subsequent integration in synthetic applications should consider both cell functionality as well as how surface topographical effects dictate and/or control such functionality. We hypothesized that a user-directed design strategy could be implemented to define surface topographies to be further used to control the density and functionality of epithelial cells. To demonstrate our hypothesis, we used polydimethylsiloxane (PDMS) replicated microtextured substrates with three degrees of densities and depths, all designed by the user, and evaluated the early response and organization of BEAS-2B cells exposed to such surfaces. The choice of PDMS was motivated by its known biocompatibility and ease in implementation for creation of engineered cellular scaffolds [26; 27].