Table 2.
Summary of physical substrate modifications highlighted in this review and their effect on the cellular response.
| Substrate modification | Ref. | Delivery (del.) method of nucleic acid | Response on transfection | Biological mechanism proposed for cell priming |
|---|---|---|---|---|
| Topography | ||||
| Micropillars (made from PMMA) on silicon | 118 | Bolus del. of FITC-labeled dextran | Increase in dextran internalization of hMSC and COS7 by ∼20 and ∼10%, respectively, in comparison to a smooth control (1 mg/mL) | Cytoskeletal organization, macropinocytosis bias |
| Micropillars (made from PDMS) | 124 | Bolus del. of LF2000-plasmid DNA complexes | Increase in transfection of NHDFs by 25% in comparison to cells cultured on smooth substrates | Cell spreading |
| Nanopillars (made from PMMA) on silicon | 118 | Bolus del. of LF2000-plasmid DNA complexes | Increase in transfection of hMSCs by 2% in comparison to cells cultured on smooth substrates | Cytoskeletal organization |
| Nanowires (made from silicon) | 123 | SMD of naked DNA plasmid | Increase in transfection of hDPSCs, HEK293, HFF, and HeLa on 3.5 µm tall columns by up to 80% in comparison to all other heights | Cell viability, enhancing proliferation, filopodia production, cell spreading |
| Nanosheets (made from silica on silicon) | 125 | Concurrent bolus del. (added with cells) of naked DNA plasmid | Increase in transfection of hMSCs on substrates etched with NS by ∼60% in comparison to planar substrates | Enhancing migration, integrin activation |
| Microgrooves (made from PU) | 126 | Concurrent bolus del. (added with cells) of naked DNA plasmid | Increase in transfection of hMSCs by ∼50% in comparison to TCPS | Cytoskeletal organization, integrin activation |
| Stiffness | ||||
| Alginate hydrogels with RGD | 29 | Bolus del. of PEI-plasmid DNA complexes | Increase in transfection of MC3T3-E1 preosteoblasts cultured on stiff substrates by 4-fold in comparison to those on soft substrates | Enhancing proliferation |
| PEGDA hydrogels | 128 | Bolus del. of linear PEI-plasmid DNA complexes | Increase in transfection of NIH/3T3 fibroblasts, D1 bone marrow stromal (BMSCs) cells, and C2C12 myoblasts cultured on stiff substrates in comparison to those on soft substrates | Cytoskeletal organization, enhancing internalization |
| Anhydride-functionalized silicone hydrogels | 129 | Bolus del. of LF2000-plasmid DNA complexes | Increase in transfection of hASCs cultured on stiff substrates by 3-fold in comparison to those on soft substrates | Cell spreading, focal adhesion formation, caveolae-mediated endocytosis bias |
FITC: fluorescein isothiocyanate; PEGDA: poly(ethylene glycol) diacrylate; RGD: arginyl-glycyl-aspartic acid; PMMA: poly(methyl methacrylate); PEI: polyethylenimine; PU: polyurethane.