The surface microtexture of an orthopaedic device can regulate cellular adhesion, a process fundamental in the initiation of osteoinduction and osteogenesis. Advances in fabrication techniques have evolved to include the field of surface modification; in particular, nanotechnology has allowed for the development of experimental nanoscale substrates for investigation into cell nanofeature interactions. Here primary human osteoblasts (HOBs) were cultured on ordered nanoscale groove/ridge arrays fabricated by photolithography. Grooves were 330 nm deep and either 10, 25 or 100 mm in width. Adhesion subtypes in HOBs were quantified by immunofluorescent microscopy and cell-substrate interactions were investigated via immunocytochemistry with scanning electron microscopy. To further investigate the effects of these substrates on cellular function, 1.7 K gene microarray analysis was used to establish gene regulation profiles of mesenchymal stem cells cultured on these nanotopographies. Nanotopographies significantly affected the formation of focal complexes (FXs), focal adhesions (FAs) and supermature adhesions (SMAs). Planar control substrates induced widespread adhesion formation; 100 mm wide groove/ridge arrays did not significantly affect adhesion formation yet induced upregulation of genes involved in skeletal development and increased osteospecific function; 25 mm wide groove/ridge arrays were associated with a reduction in SMA and an increase in FX formation; and 10 mm wide groove/ridge arrays significantly reduced osteoblast adhesion and induced an interplay of up -and downregulation of gene expression. This study indicates that groove/ridge topographies are important modulators of both cellular adhesion and osteospecific function and, critically, that groove/ridge width is important in determining cellular response.
The understanding of cellular response to the shape of their environment would be of benefit in the development of artificial extracellular environments for potential use in the production of biomimetic surfaces. Specifically, the understanding of how cues from the extracellular environment can be used to understand stem cell differentiation would be of special interest in regenerative medicine.In this paper, the genetic profile of mesenchymal stem cells cultured on two osteogenic nanoscale topographies (pitted surface versus raised islands) are compared with cells treated with dexamethasone, a corticosteroid routinely used to stimulate bone formation in culture from mesenchymal stem cells, using 19k gene microarrays as well as 101 gene arrays specific for osteoblast and endothelial biology.The current studies show that by altering the shape of the matrix a cell response (genomic profile) similar to that achieved with chemical stimulation can be elicited. Here, we show that bone formation can be achieved with efficiency similar to that of dexamethasone with the added benefit that endothelial cell development is not inhibited. We further show that the mechanism of action of the topographies and dexamethasone differs. This could have an implication for tissue engineering in which a simultaneous, targeted, development of a tissue, such as bone, without the suppression of angiogenesis to supply nutrients to the new tissue is required. The results further demonstrate that perhaps the shape of the extracellular matrix is critical to tissue development.
Telstra Creator Space is a University makerspace located at the University of Melbourne's innovation precinct, Melbourne Connect. It is accessible to students and staff from the Faculty of Engineering and Information Technology (FEIT) and to Melbourne Connect tenants to; design, fabricate and test their early prototypes.The University of Melbourne has appointed QinetiQ Australia to manage the operations of Telstra Creator Space and drive engagement with the broader FEIT.
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