Biomimetic Graphene/Spongin Scaffolds for Improved Osteoblasts Bioactivity via Dynamic Mechanical Stimulation

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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A Role for Acid-sensing Ion Channel 3, but Not Acid-sensing Ion Channel 2, in Sensing Dynamic Mechanical Stimuli

Anesthesiology ◽

10.1097/aln.0b013e3181eaa58a ◽

2010 ◽

Vol 113 (3) ◽

pp. 647-654 ◽

Cited By ~ 6

Author(s):

Jasenka Borzan ◽

Chengshui Zhao ◽

Richard A. Meyer ◽

Srinivasa N. Raja

Keyword(s):

Ion Channel ◽

Nerve Injury ◽

Mechanical Stimulation ◽

Knockout Mice ◽

Spinal Nerve ◽

Spinal Nerve Ligation ◽

Mechanical Stimuli ◽

Baseline Sensitivity ◽

Male And Female ◽

Dynamic Mechanical

Background Acid-sensing ion channels 2 and 3 (ASIC2 and ASIC3, respectively) have been implicated as putative mechanotransducers. Because mechanical hyperalgesia is a prominent consequence of nerve injury, we tested whether male and female ASIC2 or ASIC3 knockout mice have altered responses to mechanical and heat stimuli at baseline and during the 5 weeks after spinal nerve ligation. Methods Age-matched, adult male and female ASIC2 knockout (n=21) and wild-type (WT; n=24) mice or ASIC3 knockout (n=20) and WT (n=19) mice were tested for sensitivity to natural stimuli before and after spinal nerve ligation surgery. All animals were first tested for baseline sensitivity to mechanical and heat stimuli and in a novel dynamic mechanical stimulation test. The same testing procedures were then repeated weekly after spinal nerve injury. Results Compared with their respective WT counterparts, ASIC2 and ASIC3 knockout mice had normal baseline sensitivity to standard mechanical and heat stimuli. However, when exposed to a novel stroking stimulus to test sensitivity to dynamic mechanical stimulation, ASIC3 knockout mice were significantly more sensitive than were WT mice. After spinal nerve ligation, ASIC2 and ASIC3 knockout mice developed mechanical and heat hyperalgesia comparable with that of their respective WT controls. In addition, in both experiments, female mice were more sensitive than male mice to heat at baseline and after the nerve injury. Conclusions We conclude that ASIC2 and ASIC3 channels are not directly involved in the development or maintenance of neuropathic pain after spinal nerve ligation. However, the ASIC3 channel significantly modulates the sensing of dynamic mechanical stimuli in physiologic condition.

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A bioreactor for the dynamic mechanical stimulation of vocal‐fold fibroblasts based on vibro‐acoustography

The Journal of the Acoustical Society of America ◽

10.1121/1.4785691 ◽

2005 ◽

Vol 118 (3) ◽

pp. 2005-2005

Author(s):

Roger W. Chan ◽

Maritza Rodriguez

Keyword(s):

Mechanical Stimulation ◽

Vocal Fold ◽

Dynamic Mechanical ◽

Stimulation Of

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Immunomodulatory polymeric scaffold enhances extracellular matrix production in cell co-cultures under dynamic mechanical stimulation

Acta Biomaterialia ◽

10.1016/j.actbio.2015.05.038 ◽

2015 ◽

Vol 24 ◽

pp. 74-86 ◽

Cited By ~ 25

Author(s):

K.G. Battiston ◽

R.S. Labow ◽

C.A. Simmons ◽

J.P. Santerre

Keyword(s):

Extracellular Matrix ◽

Mechanical Stimulation ◽

Dynamic Mechanical ◽

Polymeric Scaffold ◽

Extracellular Matrix Production ◽

Matrix Production

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Microfluidic artificial “vessels” for dynamic mechanical stimulation of mesenchymal stem cells

Integrative Biology ◽

10.1039/c2ib00171c ◽

2012 ◽

Vol 4 (12) ◽

pp. 1487-1497 ◽

Cited By ~ 30

Author(s):

Jing Zhou ◽

Laura E. Niklason

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mechanical Stimulation ◽

Dynamic Mechanical ◽

Stimulation Of

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The influence of biological motifs and dynamic mechanical stimulation in hydrogel scaffold systems on the phenotype of chondrocytes

Biomaterials ◽

10.1016/j.biomaterials.2010.10.017 ◽

2011 ◽

Vol 32 (6) ◽

pp. 1508-1516 ◽

Cited By ~ 45

Author(s):

Taly P. Appelman ◽

Joseph Mizrahi ◽

Jennifer H. Elisseeff ◽

Dror Seliktar

Keyword(s):

Mechanical Stimulation ◽

Hydrogel Scaffold ◽

Dynamic Mechanical

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Combinatorial screen of dynamic mechanical stimuli for predictive control of MSC mechano-responsiveness

Science Advances ◽

10.1126/sciadv.abe7204 ◽

2021 ◽

Vol 7 (19) ◽

pp. eabe7204

Author(s):

Haijiao Liu ◽

Jenna F. Usprech ◽

Prabu Karthick Parameshwar ◽

Yu Sun ◽

Craig A. Simmons

Keyword(s):

Mechanical Stimulation ◽

Interactive Effect ◽

Three Dimensional ◽

Mechanical Stimuli ◽

Dynamic Mechanical ◽

Response Data ◽

Deformable Membrane ◽

Matrix Production ◽

Strain Magnitude ◽

The Individual

Mechanobiological-based control of mesenchymal stromal cells (MSCs) to facilitate engineering and regeneration of load-bearing tissues requires systematic investigations of specific dynamic mechanical stimulation protocols. Using deformable membrane microdevice arrays paired with combinatorial experimental design and modeling, we probed the individual and integrative effects of mechanical stimulation parameters (strain magnitude, rate at which strain is changed, and duty period) on myofibrogenesis and matrix production of MSCs in three-dimensional hydrogels. These functions were found to be dominantly influenced by a previously unidentified, higher-order interactive effect between strain magnitude and duty period. Empirical models based on our combinatorial cue-response data predicted an optimal loading regime in which strain magnitude and duty period were increased synchronously over time, which was validated to most effectively promote MSC matrix production. These findings inform the design of loading regimes for MSC-based engineered tissues and validate a broadly applicable approach to probe multifactorial regulating effects of mechanobiological cues.

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Incorporation of Elastin to Improve Polycaprolactone-Based Scaffolds for Skeletal Muscle via Electrospinning

Polymers ◽

10.3390/polym13091501 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1501

Author(s):

Victor Perez-Puyana ◽

Paula Villanueva ◽

Mercedes Jiménez-Rosado ◽

Fernando de la Portilla ◽

Alberto Romero

Keyword(s):

Mechanical Properties ◽

Skeletal Muscle ◽

Cell Proliferation ◽

Mechanical Stimulation ◽

Muscle Regeneration ◽

Skeletal Muscle Regeneration ◽

Dynamic Mechanical ◽

Fiber Size ◽

Cell Incubation ◽

Biological Tests

Skeletal muscle regeneration is increasingly necessary, which is reflected in the increasing number of studies that are focused on improving the scaffolds used for such regeneration, as well as the incubation protocol. The main objective of this work was to improve the characteristics of polycaprolactone (PCL) scaffolds by incorporating elastin to achieve better cell proliferation and biocompatibility. In addition, two cell incubation protocols (with and without dynamic mechanical stimulation) were evaluated to improve the activity and functionality yields of the regenerated cells. The results indicate that the incorporation of elastin generates aligned and more hydrophilic scaffolds with smaller fiber size. In addition, the mechanical properties of the resulting scaffolds make them adequate for use in both bioreactors and patients. All these characteristics increase the biocompatibility of these systems, generating a better interconnection with the tissue. However, due to the low maturation achieved in biological tests, no differences could be found between the incubation with and without dynamic mechanical stimulation.

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