The development of homogenously nano-patterned chemically modified surfaces that can be used to initiate a cellular response, particularly stem cell differentiation, in a highly controlled manner without the need for exogenous biological factors has never been reported, due to that fact that precisely defined and reproducible systems have not been available that can be used to study cell/material interactions and unlock the potential of a material driven cell response. Until now material driven stem cell (furthermore any cell) responses have been variable due to the limitations in definition and reproducibility of the underlying substrate and the lack of true homogeneity of modifications that can dictate a cellular response at a sub-micron level that can effectively control initial cell interactions of all cells that contact the surface. Here we report the successful design and use of homogenously molecularly nanopatterned surfaces to control initial stem cell adhesion and hence function. The highly specified nano-patterned arrays were compared directly to silane modified bulk coated substrates that have previously been proven to initiate mesenchymal stem cell (MSC) differentiation in a heterogenous manner, the aim of this study was to prove the efficiency of these previously observed cell responses could be enhanced by the incorporation of nano-patterns. Nano-patterned surfaces were prepared by Dip Pen Nanolithography® (DPN®) to produce arrays of 70 nm sized dots separated by defined spacings of 140, 280 and 1000 nm with terminal functionalities of carboxyl, amino, methyl and hydroxyl and used to control cell growth. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and will change the capabilities for stem cell definition in vitro and then cell based medical therapies. In addition to highlighting the ability of the materials to control stem cell functionality on an unprecedented scale this research also introduces the successful scale-up of DPN® and the novel chemistries and systems to facilitate the production of homogeneously patterned substrates (5 mm2) that are applicable for use in in vitro cell conditions over prolonged periods for complete control of material driven cell responses.
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
Balasundaram G, Webster TJ. Increased osteoblast adhesion on nanograined Ti modified with KRSR. J Biomed Mater Res. 2007;80:602–11.CrossRefGoogle Scholar
Blummel J, et al. Protein repellent properties of covalently attached PEG coatings on nanostructured SiO(2)-based interfaces. Biomaterials. 2007;28:4739–47.CrossRefPubMedGoogle Scholar
Ernsting MJ, Labow RS, Santerre JP. Human monocyte adhesion onto RGD and PHSRN peptides delivered to the surface of a polycarbonate polyurethane using bioactive fluorinated surface modifiers. J Biomed Mater Res. 2007;83:759–69.CrossRefGoogle Scholar
Kimura K, et al. Stimulation of corneal epithelial migration by a synthetic peptide (PHSRN) corresponding to the second cell-binding site of fibronectin. Invest Ophth Vis Sci. 2007;48:1110–8.CrossRefGoogle Scholar
Salber J, et al. Influence of different ECM mimetic peptide sequences embedded in a nonfouling environment on the specific adhesion of human-skin keratinocytes and fibroblasts on deformable substrates. Small. 2007;3:1023–31.CrossRefPubMedGoogle Scholar
Curtis AS, Dalby MJ, Gadegaard N. Nanoprinting onto cells. J Roy Soc Interface. 2006;3:393–8.CrossRefGoogle Scholar
Barbucci R, et al. Micro and nano-structured surfaces. J Mater Sci. 2003;14:721–5.Google Scholar
Dalby MJ, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6:997–1003.CrossRefPubMedADSGoogle Scholar
Curran JM, Chen R, Hunt JA. The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrate. Biomaterials. 2006;27:4783–93.CrossRefPubMedGoogle Scholar
Cavalcanti-Adam EA, Tomakidi P, Bezler M, Spatz JP. Geometric organization of the extracellular matrix in the control of integrin-mediated adhesion and cell function in osteoblasts. Prog Orthod. 2005;6:232–7.PubMedGoogle Scholar
Cavalcanti-Adam EA, et al. Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys J. 2007;92:2964–74.CrossRefPubMedGoogle Scholar
Dobereiner HG, Dubin-Thaler BJ, Giannone G, Sheetz MP. Force sensing and generation in cell phases: analyses of complex functions. J Appl Physiol. 2005;98:1542–6.CrossRefPubMedGoogle Scholar
Guignandon A, Boutahar N, Rattner A, Vico L, Lafage-Proust MH. Cyclic strain promotes shuttling of PYK2/Hic-5 complex from focal contacts in osteoblast-like cells. Biochem Biophys Res Commun. 2006;343:407–14.CrossRefPubMedGoogle Scholar
Sun Z, et al. Mechanical properties of the interaction between fibronectin and alpha5beta1-integrin on vascular smooth muscle cells studied using atomic force microscopy. Am J Physiol. 2005;289:H2526–35.Google Scholar