Abstract
Upon contact with a biomaterial, cells and surrounding tissues respond in a manner dictated by the physicochemical and mechanical properties of the material. Traditionally, cellular responses are monitored using invasive analytical methods that report the expression of genes or proteins. These analytical methods involve assessing commonly used markers for a predefined readout, masking the actual situation induced in the cells. Hence, a broader expression profile of the cellular response should be envisioned, which technically limits up scaling to higher throughput systems. However, it is increasingly recognized that morphometric readouts, obtained non-invasively, are related to gene expression patterns. Here, we introduced distinct surface roughness to three PLA surfaces, by exposure to oxygen plasma of different duration times. The response of mesenchymal stromal cells was compared to smooth untreated PLA surfaces without the addition of differentiation agents. Morphological and genome wide expression profiles revealed underlying cellular changes which was hidden for the commonly used gene markers for osteo-, chondro- and adipogenesis. Using 3 morphometric parameters, obtained by high content imaging, we were able to build a classifier and discriminate between oxygen plasma-induced modified sheets and non-modified PLA sheets where evaluating classical candidates missed this effect. This approach shows the feasibility to use noninvasive morphometric data in high-throughput systems to screen biomaterial surfaces indicating the underlying genetic biomaterial-induced changes.
Original language | English |
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Pages (from-to) | 1498-1505 |
Number of pages | 8 |
Journal | Biomaterials |
Volume | 34 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Feb 2013 |
Externally published | Yes |
Funding
The authors acknowledge the Marie Curie Early Stage training program JOIN(ed)T for funding of H.U., STW for funding JdB, TeRM for A.B. and J.D. and the BMM program for N.G. We wish to acknowledge Anne Carpenter and colleagues for their kind assistance with CellProfiler software, Dr. Auke Renard from Medisch Spectrum Twente for kindly providing us with bone marrow aspirates, André Uitterlinden for access to and assistance with Illumina microarray facility. We are also grateful to Vinod Subramaniam, Martin Bennink and Kim Sweers for assistance with atomic force microscopy and Dr. René Kalio from Folienwerk Wolfen GmbH (Wolfen, Germany) for kindly providing the materials.
Keywords
- Cell morphology
- Gene expression
- Mesenchymal stem cell
- Molecular imaging
- Polylactic acid
- Surface roughness