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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]