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Table 5 Mechanical stimulation and gene delivery. Research papers assessing the effect of different mechanical loading regimens on non-viral-mediated gene delivery

From: Physical and mechanical cues affecting biomaterial-mediated plasmid DNA delivery: insights into non-viral delivery systems

Type of mechanical stimulation

Cell type

Transfection system

Change in transfection efficiency

Ref.

Uniaxial cyclic stretch (0-10%, 0.5 Hz, 60 min), equiaxial cyclic stretch (5%, 05. Hz, 15 min) and shear stress (0.5 3 degrees torsion, 0.5 Hz, 15 min)

Murine primary lung epithelial cells on silicone membranes

Cationic polymer TurboFect™ (ThermoFisher) or naked DNA added after loading

Independently on the type of stimulus, optimal loading regimens increased transfection efficiency, compared to less intense or more intense regimens (in terms of % time, loading time and frequency), for both polyplexes and naked DNA.

Using TurboFect™, % transfection was 63% for mechanically loaded samples and 5%, for non-loaded control.

[217]

Sine Wave Generator, 100 Hz, 10 V amplitude for 4 min

Myelogenous leukaemia cell line K562 in suspension

Naked siRNA added during loading

10-time fold increase in transfection efficiency in mechanically loaded samples, compared to non-loaded control

[218]

Uniaxial cyclic stretch, equiaxial cyclic stretch and shear stress bioreactors

Dendritic cells and mesenchymal stem cells on silicone membranes

TurboFect™ or Lipofectamine™ added after loading

Equiaxial cyclic stretch loading combined with Lipofectamine™ led to the highest transfection efficiency (60.21% for MSCs, and 65.06% for dendritic cells)

[219]

Uniaxial stretching (10%, 0.5 Hz, 30 min)

HEK 293 on silicone membranes

Naked DNA added after loading

Uniaxial stretching allowed internalisation of naked DNA, resulting in transfection efficiency of 47%. No results shown for non-loaded controls

[220]

Stretching or compression (compressing ratio 2%, 4%, 6% and stretching ratio 4%, 8%, 12%, 30, 60 and 100% duty cycle, 2, 10, 100, 1000 mHz, for 10 min)

A549 cells on silicone membranes

Lipofectamine™, added after mechanical loading

A 30% increase in transfection efficiency was observed for compressed samples (duty ratios 60% and 100%, loading frequency 2 mHz, compression ratio 4% and 6), compared to non-loaded control.

A 40% decrease in transfection efficiency was observed in stretched samples, compared to non-loaded control.

[38]

Ultrasound-induced mechanical stress (50 pulses of 250 μs in duration and 600 V in amplitude), combined with high electric field (electroporation)

In vivo rabbit retinas and in vitro chorioallantoic membrane

Naked DNA added during stimulation

1000-fold increase in photons/s indicating a higher expression of the marker gene luciferase in samples subjected to ultrasound and electroporation treatments, compared to samples subjected to electroporation alone.

[221]

Equibiaxial cyclic stretch (10% area stretch, 50% duty cycle, 0.5 Hz, time variable from 30 min to 24 h)

A549 on Pronectins™-treated plates

Electroporation of naked DNA, performed before mechanical loading

Twenty-four hours of cyclic stretch induced a onefold to sixfold increase in transfection, compared to non-loaded control

[222]

Equibiaxial stretch, either continuous or cyclic (10% area stretch, 10% duty cycle, 1 Hz, either 30 min or 24 h)

A549 on laminin-coated plates

Naked DNA, or lipoplexes composed of Lipofectin™ (Thermofisher) or electroporation. Transfection performed before and/or after loading

If performed before transfection, mechanical loading had no effect. If performed after transfection, cyclic—but not continuous—stretching significantly increased transfection efficiency for both Lipofectin™ and electroporation but had no effect on naked DNA delivery system. Specifically, 30 min of stretching was sufficient to achieve a 2-fold (for Lipofectin™) or even a 10-fold (for electroporation) increase in transgene expression.

[223]