Nanotopographic substrates of poly (methyl methacrylate) do not strongly influence the osteogenic phenotype of mesenchymal stem cells in vitro

PLoS One. 2014 Mar 3;9(3):e90719. doi: 10.1371/journal.pone.0090719. eCollection 2014.


The chemical, mechanical, and topographical features of the extracellular matrix (ECM) have all been documented to influence cell adhesion, gene expression, migration, proliferation, and differentiation. Topography plays a key role in the architecture and functionality of various tissues in vivo, thus raising the possibility that topographic cues can be instructive when incorporated into biomaterials for regenerative applications. In the literature, there are discrepancies regarding the potential roles of nanotopography to enhance the osteogenic phenotype of mesenchymal stem cells (MSC). In this study, we used thin film substrates of poly(methyl methacrylate) (PMMA) with nanoscale gratings to investigate the influence of nanotopography on the osteogenic phenotype of MSCs, focusing in particular on their ability to produce mineral similar to native bone. Topography influenced focal adhesion size and MSC alignment, and enhanced MSC proliferation after 14 days of culture. However, the osteogenic phenotype was minimally influenced by surface topography. Specifically, alkaline phosphatase (ALP) expression was not increased on nanotopographic films, nor was calcium deposition improved after 21 days in culture. Ca: P ratios were similar to native mouse bone on films with gratings of 415 nm width and 200 nm depth (G415) and 303 nm width and 190 nm depth (G303). Notably, all surfaces had Ca∶P ratios significantly lower than G415 films. Collectively, these data suggest that, PMMA films with nanogratings are poor drivers of an osteogenic phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Analysis of Variance
  • Calcium / metabolism
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Focal Adhesions / chemistry
  • Focal Adhesions / drug effects
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Microscopy, Atomic Force
  • Microscopy, Electron, Scanning
  • Microscopy, Fluorescence
  • Nanostructures / chemistry*
  • Osteogenesis / physiology*
  • Phenotype*
  • Polymethyl Methacrylate / chemistry*
  • Polymethyl Methacrylate / pharmacology


  • Polymethyl Methacrylate
  • Alkaline Phosphatase
  • Calcium

Grants and funding

This work was funded by start-up funds from the University of Michigan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.