2D and 3D Nanopatterning of Titanium for Enhancing Osteoinduction of Stem Cells at Implant Surfaces

Sjöström, Terje; McNamara, Laura E.; Meek, R.M. Dominic; Dalby, Matthew J.; Su, Bo

doi:10.1002/adhm.201200353

Cited by 92 publications

(78 citation statements)

References 43 publications

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“…20 If the situation is similar with the 8 nm topography, it seems likely that the inter-feature regions would be more effective at initiating adhesion formation due to the restrictive diameter of the topographical features, which could account for the reduced osteogenic capacity of this substrate compared to the 15 nm features with larger diameter. 4 Furthermore, in view of the theory that the convex membrane curvature (such as that induced by nanopits) can be sensed by depolarisation of ion channels, and that the concave membrane curvature (such as that induced by nanopillars) can potentially be detected by BAR (Bin–amphiphysin-Rvs) domain proteins, 21 the shape of the cell membrane over these features could also be a crucial determinant of the downstream cellular response. If the smaller feature height is also less efficient at inducing a mechanoresponse via such mechanisms, this could be having a dual effect on reducing the osteogenic effect of the substrate.…”

Section: Discussionmentioning

confidence: 99%

“…The 8- and 15 nm-high pillars were fabricated on commercially pure Grade 1 Ti discs (Titanium Metals UK) using block copolymer masking, as described in Sjöström et al 4 Briefly, poly(styrene-b-4-vinylpyridine; PS-b-P4VP) solution was spin-coated onto the Ti discs (2000 r/min, 60 s), and the surfaces were exposed to tetrahydrofuran vapour (3 h at room temperature in a sealed glass vessel), prior to rapid air-drying of the polymer. Ti samples were anodised at room temperature in 0.01 M oxalic acid, and the cathode was a platinum strip.…”

Section: Methodsmentioning

confidence: 99%

“…5,6 In a follow-up study, the feature height was reduced to 8 nm to investigate whether this would enhance the osteogenic effect even further. 4 Interestingly, however, the osteogenic effect was diminished at 8 nm, but was still enhanced compared to planar control materials. Relative to cells on the 15 nm pillars, cells on the 8 nm pillars had a reduced abundance of the bone marker osteocalcin, and fewer of the largest sized super-mature cell adhesions.…”

Section: Introductionmentioning

confidence: 98%

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Investigation of the limits of nanoscale filopodial interactions

et al. 2014

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Mesenchymal stem cells are sensitive to changes in feature height, order and spacing. We had previously noted that there was an inverse relationship between osteoinductive potential and feature height on 15-, 55- and 90 nm-high titania nanopillars, with 15 nm-high pillars being the most effective substrate at inducing osteogenesis of human mesenchymal stem cells. The osteoinductive effect was somewhat diminished by decreasing the feature height to 8 nm, however, which suggested that there was a cut-off point, potentially associated with a change in cell–nanofeature interactions. To investigate this further, in this study, a scanning electron microscopy/three-dimensional scanning electron microscopy approach was used to examine the interactions between mesenchymal stem cells and the 8 and 15 nm nanopillared surfaces. As expected, the cells adopted a predominantly filopodial mode of interaction with the 15 nm-high pillars. Interestingly, fine nanoscale membrane projections, which we have termed ‘nanopodia,’ were also employed by the cells on the 8 nm pillars, and it seems that this is analogous to the cells ‘clinging on with their fingertips’ to this scale of features.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Investigation of the limits of nanoscale filopodial interactions

et al. 2014

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“…Recently, multi-scale patterned substrates have been shown to control adhesion and differentiation of human mesenchymal stem cells [22] and topographical features combined with hyaluronic acid have been shown to enhance chondrogenic differentiation of dental pulp stem cells [23]. Furthermore, two-dimensional and three-dimensional patterning technologies have been shown to enhance osteo-induction of stem cells [24], whilst proliferation and osteogenic differentiation of human mesenchymal stem cells have been shown to be dependent on the size of the underlying structures [25]. However, optimal feature geometries and conformations (e.g.…”

Section: Introductionmentioning

confidence: 99%

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

et al. 2015

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractControlling the cell-substrate interactions at the bio-interface is becoming an inherent element in the design of implantable devices. Modulation of cellular adhesion in vitro, through topographical cues, is a well-documented process that offers control over subsequent cellular functions. However, it is still unclear whether surface topography can be translated into a clinically functional response in vivo at the tissue / device interface. Herein, we demonstrated that anisotropic substrates with a groove depth of ~317 nm and ~1,988 nm promoted human tenocyte alignment parallel to the underlying topography in vitro. However, the rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the expression of chondrogenic and osteogenic genes, indicating possible tenocyte trans-differentiation. Of significant importance is that none of the topographies assessed (~37 nm, ~317 nm and ~1,988 nm groove depth) induced extracellular matrix orientation parallel to the substrate orientation in a rat patellar tendon model. These data indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for organised neotissue formation in vivo, should multifactorial approaches that consider both surface topography and substrate rigidity be established.

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“…An elegant method to control the spatial density of bioactive peptides and the orientation of immobilized ligands is a dip-coating technique based on self-assembly of diblock copolymer micelles (block copolymer micelle nanolithography, BCMN) [30]. Using gold as the micelle core, a hexagonally ordered pattern of gold nanoparticles can be created on various materials, including orthopedically relevant surfaces, for example Ti, and used to direct cell adhesion [31,32].…”

Section: Introductionmentioning

confidence: 99%

Investigation of early cell–surface interactions of human mesenchymal stem cells on nanopatterned β-type titanium–niobium alloy surfaces

et al. 2014

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Multi-potent adult mesenchymal stem cells (MSCs) derived from bone marrow have therapeutic potential for bone diseases and regenerative medicine. However, an intrinsic heterogeneity in their phenotype, which in turn results in various differentiation potentials, makes it difficult to predict the response of these cells. The aim of this study is to investigate initial cell–surface interactions of human MSCs on modified titanium alloys. Gold nanoparticles deposited on β-type Ti–40Nb alloys by block copolymer micelle nanolithography served as nanotopographical cues as well as specific binding sites for the immobilization of thiolated peptides present in several extracellular matrix proteins. MSC heterogeneity persists on polished and nanopatterned Ti–40Nb samples. However, cell heterogeneity and donor variability decreased upon functionalization of the gold nanoparticles with cyclic RGD peptides. In particular, the number of large cells significantly decreased after 24 h owing to the arrangement of cell anchorage sites, rather than peptide specificity. However, the size and number of integrin-mediated adhesion clusters increased in the presence of the integrin-binding peptide (cRGDfK) compared with the control peptide (cRADfK). These results suggest that the use of integrin ligands in defined patterns could improve MSC-material interactions, not only by regulating cell adhesion locally, but also by reducing population heterogeneity.

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2D and 3D Nanopatterning of Titanium for Enhancing Osteoinduction of Stem Cells at Implant Surfaces

Cited by 92 publications

References 43 publications

Investigation of the limits of nanoscale filopodial interactions

Investigation of the limits of nanoscale filopodial interactions

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

Investigation of early cell–surface interactions of human mesenchymal stem cells on nanopatterned β-type titanium–niobium alloy surfaces

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