# Molecular Mechanisms of Topography Sensing by Osteoblasts: An Update
###### Abstract  
Bone is a specialized tissue formed by different cell types and a multiscale, complex mineralized matrix. The architecture and the surface chemistry of this microenvironment can be factors of considerable influence on cell biology, and can affect cell proliferation, commitment to differentiation, gene expression, matrix production and/or composition. It has been shown that osteoblasts encounter natural motifs in vivo, with various topographies (shapes, sizes, organization), and that cell cultures on flat surfaces do not reflect the total potential of the tissue. Therefore, studies investigating the role of topographies on cell behavior are important in order to better understand the interaction between cells and surfaces, to improve osseintegration processes in vivo between tissues and biomaterials, and to find a better topographic surface to enhance bone repair. In this review, we evaluate the main available data about surface topographies, techniques for topographies' production, mechanical signal transduction from surfaces to cells and the impact of cell-surface interactions on osteoblasts or proosteoblasts' behavior. surface topography; osteoblasts; cell behavior; in vitro model; topography sensing; molecular transduction; bone mineralization +
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as morphogenesis, cell migration or differentiation. In addition, topography-induced cell behaviors can be harnessed to design new, osteeconductive in vitro culture system and biomaterials. In that respect, topography-mediated effects also bear an advantage in the design of new biomaterials, as they are potentially more stable than chemistry-mediated effects such as coatings, which may be rapidly degraded by the biological environment. This review will focus on the influence of local topography on osteoblast-mediated matrix mineralization and osteogenic differentiation of mesenchymal stem cells (MSCs). The bone presents a complex multiscale architecture [1; 2; 3; 4; 5] that has been detailed recently by 3D reconstruction of lamellar and fibro-lamellar bone tissue by FIB (Focused Ion Beam) and SEM (Scanning Electron Microscopy) [1]. The authors proposed that bone is made of ordered and disordered material, the former being predominant. They detailed nine levels of organization for both, ranging from the basic components of carbonated hydroxyapatite (HA), type I collagen molecules, water and low amounts of noncollagenous proteins at the nanometer scale (level I) to the cortical and trabecular bone at the macroscale (level IX). More recently, an extension in the number of organization levels of bone to twelve was proposed [6]. Although Petri dishes and glass substrates have been used for a long time and brought many important results [7; 8; 9], these flat and smooth substrates are only able to roughly reproduce up to the third or fourth level of organization proposed by [PERSON] et al. [1]. The matrix produced in those culture conditions shows, at best, aligned or alternated arrays of collagen fibrils, with osteocyteselike cells trapped inside the bulk of mineralized matrix [10; 11]. In particular, several in vivo histological features present in the cortical bone have never been reproduced in vitro. These include, for instance, osteelike layered structures formed by osteoblasts over the concave surfaces left by osteoclasts after bone resorption. Thus, the osteoblasts may encounter various geometries of different scales in vivo. It is therefore important to develop in vitro model substrates with biomimicking topographies in order to study the bone-producing behavior of osteoblasts more accurately. The reaction of osteoblasts to surface topographies is also relevant in the context of bone repair. So far, the replacement of most bone regions relies extensively on autografts. The presence of bone cells, blood vessels and calcified matrix ensures that these autografts have strong osteoinductive potential. However, the risk of morbidity and infection calls for the development of biomaterial-based synthetic grafts.