Nanoscale Stimulation of Osteoblastogenesis from Mesenchymal Stem Cells: Nanotopography and Nanokicking

Pemberton, Gabriel D.; Childs, Peter; Reid, S.; Nikukar, Habib; Tsimbouri, Penelope; Gadegaard, Nikolaj; Curtis, Adam; Dalby, Matthew J.

doi:10.2217/nnm.14.134

Cited by 28 publications

(37 citation statements)

References 56 publications

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“…Since we know the surface area of the cantilever tip (10 µm radius) we can estimate that a cuboidal cell of 140 × 100 µm would receive a peak force of 17 nN due to this vibration (9 nm, 1 kHz). It is worth noting that this measurement is largely consistent with our previously calculated estimates in the 10s of nN for vibration of 30 nm at 1 kHz [20][21][22]40 .…”

Section: Afm Measurements Of Collagen Gel During Nanovibrationsupporting

confidence: 91%

“…These factors are important when using nanoscale amplitudes as consistent vibration ensures that all cells on the bioreactor experience the same levels of acceleration. Previous experiments [19][20][21][22][23] used vibration amplitudes of 15 -35 nm and frequencies of 1 Hz -5 kHz and the most significant osteogenic effects were observed at 1 kHz 20,22 . It is important that the bioreactor operates within this frequency range and crucial that this range is well below the bioreactor's resonant condition to avoid resonant amplification/damping.…”

Section: Introductionmentioning

confidence: 99%

“…Initial studies from Curtis et al 19 and Nikukar et al 20 conducted using vibration amplitudes of tens of nanometres showed that endothelial cells and MSCs are sensitive to vibrations of this level. To achieve nanometre vibrations, several studies [19][20][21][22] used a single piezo actuator, single Petri dish apparatus to produce accurate vertical vibration over a small growth surface, however this imposed limitations of scale and vibration amplitude which become relevant if developing towards a larger industrial process. The use of alternative growth containers (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

Campsie

Childs

Robertson

et al. 2019

Preprint

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In regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of mesenchymal stem cells (MSCs) has been shown to activate mechanotransduction pathways stimulating osteogenesis in 2D and 3D culture. This has the potential to revolutionise bone graft procedures by creating cellular graft material from autologous or allogeneic sources of MSCs without using chemical induction. With the increased interest in mechanical stimulation of cells and huge potential for clinical use, it is apparent that researchers and clinicians require a scalable bioreactor system that provides consistently reproducible results with a simple turnkey approach. A novel bioreactor system is presented that consists of: a bioreactor vibration plate, calibrated and optimised for nanometre vibrations at 1 kHz, a power supply unit, which supplies a 1 kHz sine wave signal necessary to generate approximately 30 nm of vibration amplitude, and custom 6-well cultureware with toroidal shaped magnets incorporated in the base of each well for conformal attachment to the bioreactor's magnetic vibration plate. The cultureware and vibration plate were designed using finite element analysis to determine the modal and harmonic responses, and validated by interferometric measurement. This helps ensure that the vibration plate and cultureware, and thus collagen and MSCs, all move as a rigid body, avoiding large deformations close to the resonant frequency of the vibration plate and vibration damping beyond the resonance. Assessment of osteogenic protein expression was performed to confirm differentiation of MSCs after initial biological experiments with the system, as well as atomic force microscopy of the 3D gel constructs during vibrational stimulation to verify that strain hardening of the gel did not occur. This shows that cell differentiation was the result of the nanovibrational stimulation provided by the bioreactor alone, and that other cell differentiating factors, such as stiffening of the collagen gel, did not contribute.

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Section: Afm Measurements Of Collagen Gel During Nanovibrationsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

Campsie

Childs

Robertson

et al. 2019

Preprint

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“…We have previously used nanoscale vibrational displacements to stimulate osteogenesis in MSCs cultured on tissue culture plastic in 2D 17,18 . This work identified that mechanical stimulation of 1000 Hz frequency with 15-nm vertical displacement promoted MSC differentiation 18 .…”

mentioning

confidence: 99%

Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor

et al. 2017

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“…In this sense, many studies have demonstrated that diverse cellular signaling cascades become activated as a consequence of mechanical stimulation, a process known as mechanotransduction (see [12,13] for reviews). Examples of these mechanical stimulations include matrix-elasticity modifications, substrate nanotopography patterns [14,15], local nanoforces (internal or external to the cell) [16,17], and nanovibrations [18][19][20][21][22]. Cells react effectively to such mechanical alterations by inducing cellular responses.…”

Section: Introductionmentioning

confidence: 99%

Design, Implementation, and Validation of a Piezoelectric Device to Study the Effects of Dynamic Mechanical Stimulation on Cell Proliferation, Migration and Morphology

Mojena-Medina

Martínez-Hernández

Fuente

et al. 2020

Sensors

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Cell functions and behavior are regulated not only by soluble (biochemical) signals but also by biophysical and mechanical cues within the cells’ microenvironment. Thanks to the dynamical and complex cell machinery, cells are genuine and effective mechanotransducers translating mechanical stimuli into biochemical signals, which eventually alter multiple aspects of their own homeostasis. Given the dominant and classic biochemical-based views to explain biological processes, it could be challenging to elucidate the key role that mechanical parameters such as vibration, frequency, and force play in biology. Gaining a better understanding of how mechanical stimuli (and their mechanical parameters associated) affect biological outcomes relies partially on the availability of experimental tools that may allow researchers to alter mechanically the cell’s microenvironment and observe cell responses. Here, we introduce a new device to study in vitro responses of cells to dynamic mechanical stimulation using a piezoelectric membrane. Using this device, we can flexibly change the parameters of the dynamic mechanical stimulation (frequency, amplitude, and duration of the stimuli), which increases the possibility to study the cell behavior under different mechanical excitations. We report on the design and implementation of such device and the characterization of its dynamic mechanical properties. By using this device, we have performed a preliminary study on the effect of dynamic mechanical stimulation in a cell monolayer of an epidermal cell line (HaCaT) studying the effects of 1 Hz and 80 Hz excitation frequencies (in the dynamic stimuli) on HaCaT cell migration, proliferation, and morphology. Our preliminary results indicate that the response of HaCaT is dependent on the frequency of stimulation. The device is economic, easily replicated in other laboratories and can support research for a better understanding of mechanisms mediating cellular mechanotransduction.

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Nanoscale Stimulation of Osteoblastogenesis from Mesenchymal Stem Cells: Nanotopography and Nanokicking

Cited by 28 publications

References 56 publications

Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor

Design, Implementation, and Validation of a Piezoelectric Device to Study the Effects of Dynamic Mechanical Stimulation on Cell Proliferation, Migration and Morphology

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