Use of nanoscale mechanical stimulation for control and manipulation of cell behaviour

Childs, Peter; Boyle, Christina A.; Pemberton, Gabriel D.; Nikukar, Habib; Curtis, Adam; Henriquez, Fiona L.; Dalby, Matthew J.; Reid, S.

doi:10.1016/j.actbio.2015.11.045

Cited by 28 publications

(24 citation statements)

References 106 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%

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%

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

Campsie

Childs

Robertson

et al. 2019

Preprint

Self Cite

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show abstract

“…As a consequence, survival, apoptosis, proliferation, and diferentiation properties are afected [24]. For example, MSCs were stimulated by vibration from 1 to 1000 Hz, and myogenic transcription factors were found to be upregulated by low frequencies (1 and 50 Hz), but osteogenic transcription factors were upregulated by high frequencies (500 and 1000 Hz) [25]. These data suggest that some shock absorber is needed to prevent the shocks and vibration.…”

Section: Shock and Vibration Resistancementioning

confidence: 82%

Transportation of Mesenchymal Stem Cells for Clinical Applications

Aoyama¹

2017

Mesenchymal Stem Cells - Isolation, Characterization and Applications

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Cell-processing procedures are conducted in accordance with Good Manufacturing Practices, and clinical procedures are performed by highly optimised methods. A highquality transportation system is essential for safe and efective handling of mesenchymal stem cells (MSCs) between cell-processing and transplantation stages. For MSC transportation, either frozen cell or non-frozen cell transportation is performed. There are many requirements for transporting a package by either type of transportation. In frozen cell transportation, some issues have yet to be resolved: the primary receptacle and cryoprotectant reagents. In non-frozen cell transportation, control of cell metabolism and protection from environmental changes are more serious problems. Stabilisation of temperature, shock resistance, gas control, and an ultraviolet radiation (UVR) shielding technology should be considered. The transportation system should be established in compliance with the guidelines. Both development of a high-quality transportation package and establishment of a high-quality transportation system are important for the efective use of MSCs in clinical applications.

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“…They feature extremely high piezoelectricity and sensing capabilities rendering that application of an electric field or mechanical load can be used for tuning their surface electrical charges. Thus, due to their surface electrical charges and piezoelectricity, they can interact with cells electrically or via nanoscale mechanical stimulation . Ferroelectrics neither require external power sources to manifest surface electric charges, nor electrodes, which is a clear advantage over other electroactive materials .…”

Section: Introductionmentioning

confidence: 99%

“…Thus, due to their surface electrical charges and piezoelectricity, they can interact with cells electrically or via nanoscale mechanical stimulation. [11][12][13] Ferroelectrics neither require external power sources to manifest surface electric charges, nor electrodes, which is a clear advantage over other electroactive materials. 11 Despite the enormous potential of ferroelectrics as novel "smart biomaterials," studies on their topo-physical properties, their chemistry, chemical stability, and cytotoxicity are still missing.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity, chemical stability, and surface properties of ferroelectric ceramics for biomaterials

et al. 2017

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Surface chemistry and topo-physical properties determine the interactions of biomaterials with their physiological environment. Ferroelectrics hold great promise as the next generation of scaffolds for tissue repair since they feature tunable surface electrical charges, piezoelectricity, and sensing capabilities. We investigate the topography, wettability, chemical stability, and cytotoxicity in salient ferroelectric systems such as (1Àx) (Na 1/2 Bi 1/2 )TiO 3 -xBaTiO 3 , (1Àx) showed the greatest potential leading to a cell viability of (149 AE 30)% and DNA synthesis of (299 AE 85)% in comparison to the reference. Lead leaching from Pb (Zr,Ti)O 3 negatively affected the cultured cells. Wettability and chemical stability are key factors that determine the cytotoxicity of ferroelectrics. These variables have to be considered in the design of novel electroactive scaffolds based on ferroelectric ceramics.

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Use of nanoscale mechanical stimulation for control and manipulation of cell behaviour

Cited by 28 publications

References 106 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

Transportation of Mesenchymal Stem Cells for Clinical Applications

Cytotoxicity, chemical stability, and surface properties of ferroelectric ceramics for biomaterials

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