Increasing Fibroblast Response to Materials Using Nanotopography: Morphological and Genetic Measurements of Cell Response to 13-nm-High Polymer Demixed Islands

Dalby, Matthew J.; Yarwood, Stephen J.; Riehle, Mathis O.; Johnstone, Heather; Affrossman, S.; Curtis, Adam

doi:10.1006/excr.2002.5498

Cited by 329 publications

(244 citation statements)

References 42 publications

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“…Taken together, these data provided evidence that alteration of ECM signaling or cytoskeleton arrangement could lead to a change in gene regulation directing cell differentiation. Changes in gene regulation by nanotopography in fibroblasts have also been observed on random pattern of nano-scaled islands produced with polymer-demixing techniques [26]. The difference in cytoskeleton arrangement, cell adhesion and protein expression, such as Rac and other signaling proteins, on fibroblasts cultured on nano-islands versus flat surface are observed in cDNA microarray gene expression analysis.…”

Section: Discussionmentioning

confidence: 88%

Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

Yim

Pang

Leong

2007

Experimental Cell Research

702

677

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Human mesenchymal stem cells (hMSCs) have been shown to trans-differentiate into neuronal-like cells by culture in neuronal induction media, although the mechanism is not well understood. Topography can also influence cellular responses including enhanced differentiation of progenitor cells. As extracellular matrix (ECM) in vivo comprises topography in the nanoscale, we hypothesize that nanotopography could influence stem cell differentiation into specific non-default pathways, such as transdifferentiation of hMSC. Differentiation and proliferation of hMSCs were studied on nano-gratings of 350nm width. Cytoskeleton and nuclei of hMSCs were aligned and elongated along the nano-gratings. Gene profiling and immunostaining showed significant up-regulation of neuronal markers such as microtubule-associated protein 2 (MAP2) compared to unpatterned and micropatterned controls. The combination of nanotopography and biochemical cues such as retinoic acid further enhanced the upregulation of neuronal marker expressions, but nanotopography showed a stronger effect compared to retinoic acid alone on unpatterned surface. This study demonstrated the significance of nanotopography in directing differentiation of adult stem cells.

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Section: Discussionmentioning

confidence: 88%

Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

Yim

Pang

Leong

2007

Experimental Cell Research

702

677

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“…6 Accordingly, nanogrooves, nanopits, and nanoislands have been shown to affect contact guidance in vitro and directly influence cell adhesion to a degree related to feature dimension, cell type, and cell density. [7][8][9][10] Present studies indicate that fibroblasts react significantly to nanotopographical cues in vitro, perceiving the topography of an implanted surface via dynamic filopodial formation and extension to find sites topographicaly suitable for adhesion, growth, and maturation. 11,12 The processes that mediate cellular reaction to nanoscale surface structures are not well understood, and may be direct (a result of the influence of the surface topography) or indirect (where the surface structure has affected the composition, orientation, or conformation of the adsorbed ECM components).…”

Section: Introductionmentioning

confidence: 88%

Regulation of implant surface cell adhesion: characterization and quantification of S‐phase primary osteoblast adhesions on biomimetic nanoscale substrates

Biggs

Richards

Gadegaard

et al. 2006

Journal Orthopaedic Research

109

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Integration of an orthopedic prosthesis for bone repair must be associated with osseointegration and implant fixation, an ideal that can be approached via topographical modification of the implant/bone interface. It is thought that osteoblasts use cellular extensions to gather spatial information of the topographical surroundings prior to adhesion formation and cellular flattening. Focal adhesions (FAs) are dynamic structures associated with the actin cytoskeleton that form adhesion plaques of clustered integrin receptors that function in coupling the cell cytoskeleton to the extracellular matrix (ECM). FAs contain structural and signalling molecules crucial to cell adhesion and survival. To investigate the effects of ordered nanotopographies on osteoblast adhesion formation, primary human osteoblasts (HOBs) were cultured on experimental substrates possessing a defined array of nanoscale pits. Nickel shims of controlled nanopit dimension and configuration were fabricated by electron beam lithography and transferred to polycarbonate (PC) discs via injection molding. Nanopits measuring 120 nm diameter and 100 nm in depth with 300 nm center-center spacing were fabricated in three unique geometric conformations: square, hexagonal, and near-square (300 nm spaced pits in square pattern, but with AE50 nm disorder). Immunofluorescent labeling of vinculin allowed HOB adhesion complexes to be visualized and quantified by image software. Perhipheral adhesions as well as those within the perinuclear region were observed, and adhesion length and number were seen to vary on nanopit substrates relative to smooth PC. S-phase cells on experimental substrates were identified with bromodeoxyuridine (BrdU) immunofluorescent detection, allowing adhesion quantification to be conducted on a uniform flattened population of cells within the S-phase of the cell cycle. Findings of this study demonstrate the disruptive effects of ordered nanopits on adhesion formation and the role the conformation of nanofeatures plays in modulating these effects. Highly ordered arrays of nanopits resulted in decreased adhesion formation and a reduction in adhesion length, while introducing a degree of controlled disorder present in near-square arrays, was shown to increase focal adhesion formation and size. HOBs were also shown to be affected morphologicaly by the presence and conformation of nanopits. Ordered arrays affected cellular spreading, and induced an elongated cellular phenotype, indicative of increased motility, while near-square nanopit symmetries induced HOB spreading. It is postulated that nanopits affect osteoblast-substrate adhesion by directly or indirectly affecting adhesion complex formation, a phenomenon dependent on nanopit dimension and conformation. ß

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“…Response of cells to topographical cues and the concept of contact guidance have been known for decades [8,9]. Various topographical features such as grooves, ridges, stops, pores, wells and nodes in micro-or nanoscale [10][11][12] have been presented to a wide variety of cells: fibroblasts [13][14][15][16][17], BHK cells [18], neuronal cells [19], macrophages [20,21], epithelial cells [22], endothelial cells, and smooth muscle cells (SMC) [23][24][25][26]. Topography can influence cellular responses from initial attachment and migration to differentiation and production of new tissue [10,12,27].…”

Section: Introductionmentioning

confidence: 99%

Nanopattern-induced changes in morphology and motility of smooth muscle cells

Yim¹,

et al. 2005

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Cells are known to be surrounded by nanoscale topography in their natural extracellular environment. The cell behavior, including morphology, proliferation, and motility of bovine pulmonary artery smooth muscle cells (SMC) were studied on poly(methyl methacrylate) (PMMA) and poly (dimethylsiloxane) (PDMS) surfaces comprising nanopatterned gratings with 350 nm linewidth, 700 nm pitch, and 350 nm depth. More than 90% of the cells aligned to the gratings, and were significantly elongated compared to the SMC cultured on non-patterned surfaces. The nuclei were also elongated and aligned. Proliferation of the cells was significantly reduced on the nanopatterned surfaces. The polarization of microtubule organizing centers (MTOC), which are associated with cell migration, of SMC cultured on nanopatterned surfaces showed a preference towards the axis of cell alignment in an in vitro wound healing assay. In contrast, the MTOC of SMC on non-patterned surfaces preferentially polarized towards the wound edge. It is proposed that this nanoimprinting technology will provide a valuable platform for studies in cell-substrate interactions and for development of medical devices with nanoscale features.

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Increasing Fibroblast Response to Materials Using Nanotopography: Morphological and Genetic Measurements of Cell Response to 13-nm-High Polymer Demixed Islands

Cited by 329 publications

References 42 publications

Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

Regulation of implant surface cell adhesion: characterization and quantification of S‐phase primary osteoblast adhesions on biomimetic nanoscale substrates

Nanopattern-induced changes in morphology and motility of smooth muscle cells

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