Nanotextures may help make better bone implants, tease out differentiation pathways
Techniques that hope to use stromal stem cells from the bone marrow to help repair bone run into a problem: these mesenchymal stem cells are just as apt to make soft tissues as they are to make bone cells. This means that implants introduced along with the stem cells tend to get covered in soft connective tissue rather than becoming encased in new bone.
In the laboratory, corticosteroids can be used to induce mesenchymal stem cells to make bone-producing cells, but these drugs have undesirable side-effects in patients over long periods. Now, a study led by Matthew Dalby and Nikolaj Gadegaard at the University of Glasgow and Richard Oreffo at the University of Southampton in the UK, indicates that a non-chemical technique could be nearly as good1. They have found that giving the cells a particular type of textured surface on which to grow favours their differentiation as bone-producing cells. Moreover, the work shows that cells stimulated through different techniques can still develop similar phenotypes.
Dalby et al. used electron-beam lithography to create arrays of differently spaced nanopits on polymer surfaces, then seeded the surfaces with mesenchymal stem cells. After about four weeks, cells grown on a surface with regularly spaced pits resembled connective tissue fibroblasts, but those grown on a surface where the pits were displaced slightly from a regular pattern showed typical early signs of bone nodules. Cells grown over completely randomly placed nanopits did not (see image).

Mesenchymal stem cells grown over the slightly disordered nanopits were then compared with cells treated with the corticosteroid dexamethasone and grown on a non-patterned surface. Both sets of cells had increased expression of bone-specific genes compared to untreated cells. The dexamethasone treatment did, however, activate a different set of intracellular pathways (including apoptosis, chemokine and calcium signaling) from those activated in cells grown over nanopits.
So looking at what happens on different textures could also help to uncover signaling pathways that promote the desired type of differentiation. The researchers are now investigating how nanosurfaces affect other kinds of stem cells and other differentiation pathways.
References
Dalby, M. et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nature Mater. Advance online publication 23 September 2007, 10.1038/nmat2013.
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Baker, M. Nanopits push stem cells toward bone. Nat Rep Stem Cells (2007). https://doi.org/10.1038/stemcells.2007.96
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DOI: https://doi.org/10.1038/stemcells.2007.96