Nano- and microstructured materials for in vitro studies of the physiology of vascular cells

Greiner, Alexandra M.; Sales, Adrià; Chen, Hao; Biela, Sarah; Kaufmann, Dieter; Kemkemer, Ralf

doi:10.3762/bjnano.7.155

Cited by 42 publications

(40 citation statements)

References 275 publications

(358 reference statements)

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“…Cells are generally capable of being oriented and directed, both in vivo and in vitro, by the micro-and nanotopography of their substrate in a complex feedback process known as contact guidance. [1][2][3][4][5] This phenomenon has been observed in a wide variety of settings, including organ and tissue generation and regeneration, 6 wound healing, 7,8 and axon pathfinding. 9,10 Contact guidance is also an important parameter in the design of medical implant surfaces, as tailored topography can provide a level of cellular control in vivo.…”

Section: Introductionmentioning

confidence: 99%

Initial contact guidance during cell spreading is contractility-independent

2017

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A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to perturb cytoskeletal structures. Inhibition of actomyosin contractility with the chemical inhibitor blebbistatatin demonstrated that initial contact guidance events are independent of traction force generation. However, cell alignment to the grooved substrate was altered at later time points, suggesting an initial 'passive' phase of contact guidance, followed by a contractility-dependent 'active' phase that relies on mechanosensitive feedback. The actin cytoskeleton was also perturbed in an indirect manner by culturing cells upside down, resulting in decreased levels of contact guidance and suggesting that a possible loss of contact between the actin cytoskeleton and the substrate could lead to cytoskeleton impairment. The process of contact guidance at the microscale was found to be primarily lamellipodia driven, as no bias in filopodia extension was observed on micron-scale grooves.

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Section: Introductionmentioning

confidence: 99%

Initial contact guidance during cell spreading is contractility-independent

2017

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“…Micro- and nanostructured materials for medical devices have demonstrated that surface topography as well as surface chemistry influence cellular behaviour such as adhesion, migration and proliferation [1–6]. It is important to understand and control cell behaviour by topography in order to modulate the functions of the cells.…”

Section: Introductionmentioning

confidence: 99%

Silicon microgrooves for contact guidance of human aortic endothelial cells

Fernández‐Castillejo

Formentı́n

Catalán

et al. 2017

Beilstein J. Nanotechnol.

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Background: Micro- and nanoscale substrates have been fabricated in order to study the influence of the topography on the cellular response. The aim of this work was to prepare different collagen-coated silicon substrates displaying grooves and ridges to mimic the aligned and elongated endothelium found in linear vessels, and to use them as substrates to study cell growth and behaviour. Results: The influence of groove-shaped substrates on cell adhesion, morphology and proliferation were assessed, by comparing them to flat silicon substrates, used as control condition. Using human aortic endothelial cells, microscopy images demonstrate that the cellular response is different depending on the silicon surface, when it comes to cell adhesion, morphology (alignment, circularity and filopodia presence) and proliferation. Moreover, these structures exerted no cytotoxic effect. Conclusion: The results suggest that topographical patterning influences cell response. Silicon groove substrates can be used in developing medical devices with microscale features to mimic the endothelium in lineal vessels.

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“…[8][9][10][11] Among the factors known to control cellular events, nano-topographical features play a pivotal role by exerting direct cueing on adherent cells. 2,9,10,[12][13][14][15][16][17] Based on this evidence, much effort has been invested in the design of synthetic nanostructured substrates to support the investigation of the interplay between nanotopographical cues and cellular functions. 2,10,12,13,15,18 Among the panoply of techniques developed to nanostructure biomaterials, anodization has rapidly emerged as a simple but effective electrochemical treatment to create bioactive nanostructures composed of arrays of aligned nanotubes on titanium, the gold standard in medicine.…”

Section: Introductionmentioning

confidence: 99%

“…2,9,10,[12][13][14][15][16][17] Based on this evidence, much effort has been invested in the design of synthetic nanostructured substrates to support the investigation of the interplay between nanotopographical cues and cellular functions. 2,10,12,13,15,18 Among the panoply of techniques developed to nanostructure biomaterials, anodization has rapidly emerged as a simple but effective electrochemical treatment to create bioactive nanostructures composed of arrays of aligned nanotubes on titanium, the gold standard in medicine. [18][19][20][21] The design of morphological parameters, mainly nanotube diameter, has been achieved through the modulation of experimental parameters (i.e., anodization voltage and time, composition of the electrolytic solution), permitting to rationally engineer nanotopographical features and assess their influence on cellular events.…”

Section: Introductionmentioning

confidence: 99%

<p>The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures</p>

Steeves¹,

Ho²,

Munisso³

et al. 2020

IJN

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Introduction: In recent years there has been ample interest in nanoscale modifications of synthetic biomaterials to understand fundamental aspects of cell-surface interactions towards improved biological outcomes. In this study, we aimed at closing in on the effects of nanotubular TiO 2 surfaces with variable nanotopography on the response on human mesenchymal stem cells (hMSCs). Although the influence of TiO 2 nanotubes on the cellular response, and in particular on hMSC activity, has already been addressed in the past, previous studies overlooked critical morphological, structural and physical aspects that go beyond the simple nanotube diameter, such as spatial statistics. Methods: To bridge this gap, we implemented an extensive characterization of nanotubular surfaces generated by anodization of titanium with a focus on spatial structural variables including eccentricity, nearest neighbour distance (NND) and Voronoi entropy, and associated them to the hMSC response. In addition, we assessed the biological potential of a twotiered honeycomb nanoarchitecture, which allowed the detection of combinatory effects that this hierarchical structure has on stem cells with respect to conventional nanotubular designs. We have combined experimental techniques, ranging from Scanning Electron (SEM) and Atomic Force (AFM) microscopy to Raman spectroscopy, with computational simulations to characterize and model nanotubular surfaces. We evaluated the cell response at 6 hrs, 1 and 2 days by fluorescence microscopy, as well as bone mineral deposition by Raman spectroscopy, demonstrating substrate-induced differential biological cueing at both the short-and long-term. Results: Our work demonstrates that the nanotube diameter is not sufficient to comprehensively characterize nanotubular surfaces and equally important parameters, such as eccentricity and wall thickness, ought to be included since they all contribute to the overall spatial disorder which, in turn, dictates the overall bioactive potential. We have also demonstrated that nanotubular surfaces affect the quality of bone mineral deposited by differentiated stem cells. Lastly, we closed in on the integrated effects exerted by the superimposition of two dissimilar nanotubular arrays in the honeycomb architecture. Discussion: This work delineates a novel approach for the characterization of TiO 2 nanotubes which supports the incorporation of critical spatial structural aspects that have been overlooked in previous research. This is a crucial aspect to interpret cellular behaviour on nanotubular substrates. Consequently, we anticipate that this strategy will contribute to the unification of studies focused on the use of such powerful nanostructured surfaces not only for biomedical applications but also in other technology fields, such as catalysis.

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Nano- and microstructured materials for in vitro studies of the physiology of vascular cells

Cited by 42 publications

References 275 publications

Initial contact guidance during cell spreading is contractility-independent

Initial contact guidance during cell spreading is contractility-independent

Silicon microgrooves for contact guidance of human aortic endothelial cells

<p>The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures</p>

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