Cellular Response to Semi-ordered and Biomimetic Nanotubular Surfaces

Abstract

Understanding cell behavior at the material-host tissue interface is a fundamental prerequisite for designing the next generation of biomaterials capable of directing cellular events towards a desired biological outcome (e.g. faster tissue integration). In addition, unraveling the relationship between cell activity and nanoscale surface features will further the present knowledge of the fundamental cellular mechanisms that control how cells sense and respond to natural (e.g. extracellular matrix) and synthetic (e.g. biomaterials) surfaces. It is now well-known that the nanoscale physicochemical features of surfaces dictate cell fate by affecting phenomena such as proliferation, differentiation, genetic transcription and protein translation. In particular, nanotopographical features play a pivotal role during cell-surface interactions by exerting a direct mechanotransductive effect on cells, which, in turn, dictate biochemical signaling. In this context, several studies have addressed different aspects of the relationships between nanofeatures and specific cellular functions, including morphological changes, the establishment of focal adhesions (FAs, clusters of adhesion molecules that regulate cell structure and activity, determining how cells sense and respond to natural and synthetic substrates) and differentiation. However, the precise interplay between the morphological characteristics of nontopographical features not only on the surface but also along a third dimension (height) and cellular response still needs to be fully elucidated. Once revealed, such knowledge will shed new light on how cells sense and respond to 2- and 3-dimensional nanoscale patterns. In this context, anodization, a simple yet effective electrochemical treatment, allows to engender on titanium, the gold standard in medicine, arrays of nanotubes with tailor-made diameters. Notably, although nanotubular surfaces on anodized titanium have been extensively studied in relation to their effect on cell response, none of the previous studies has precisely assessed the effects of the morphological features and geometrical arrangement of the nanotubes. This is an important aspect, since the morphological characteristics and the spatial placement of nanofeatures has been shown to control cell response. In addition, by employing the same technique (i.e. anodization), a 3-dimensional hierarchical surface that mimics the frustule (i.e. silicified cell wall) of diatoms (a type of microalgae) can be created. Aside from enabling, for the first time, cellular studies on such bioinspired surface, this hierarchical nanoscale substrate will also allow to probe the effects of a 2-tier nanotopographical gradient along the depth of the nanotubular layer.