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Table 4 Biomaterial stiffness and gene delivery. Research papers assessing the effect of biomaterial stiffness on non-viral-mediated gene delivery

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

Biomaterial

Cell type

Transfection system

Change in transfection efficiency

Ref.

MAP hyaluronic acid hydrogels of different stiffness

Human dermal fibroblasts

jetPEI®

Stiffer hydrogels resulted in a cumulative transgene expression (luminescence) of 2 × 107.

Softer hydrogels resulted in a cumulative transgene expression (luminescence) of 1 × 107.

[185]

PLGA porous scaffolds of different stiffness

Human ADSCs

Chitosan polyplexes

Transgene expression was 2-fold higher in stiffer scaffolds, compared to soft ones.

[188]

Alginate gels of different stiffness, conjugated with RGDSP peptides substrates

murine preosteoblasts

PEI polyplexes

Transgene expression 4 times higher in stiffer substrates compared to soft ones.

[189]

Gelatin-coated silicone hydrogels of different stiffness

Human ADSCs

Nanolipoplexes added in the culture medium

Nanolipoplexes were more efficiently internalised in stiffer substrates (∼70 ng internalised per stiff scaffold, compared to 60 ng per soft scaffolds)

[190]

PEGDA hydrogels of different stiffness

NIH3T3 murine fibroblasts, BMSCs, and C2C12 skeletal myoblasts

PEI polyplexes

Stiffer hydrogels led to higher transgene production:

700 ng in stiff hydrogels and 400 ng in soft hydrogels, for fibroblasts.

200 ng in stiff hydrogels and 100 ng in soft hydrogels, for BMSCs.

100 ng in stiff hydrogels and ∼ 50 ng in soft hydrogels, for C2C21

[191]

Hyaluronic acid hydrogels of different stiffness

Murine MSCs

PEI polyplexes

Soft hydrogels led to a higher transgene expression (luminescence ∼ 5 × 105), compared to stiff ones (luminescence ∼ 1 × 105)

[161]

3D collagen-I-alginate hydrogels, of different stiffness and collagen: alginate ratios

Human BMSCs

3D-FectINâ„¢ (OZ Biosciences)

Stiff hydrogels led to a 5,000-fold increase in transgene expression, compared to cells transfected using 2D systems.

At collagen: alginate ratio (1:2), transgene expression in stiff hydrogels was 20-fold higher, than in soft ones.

[14]