Substrate-mediated gene delivery

Gene delivery from polymeric biomaterials forming the scaffold can be due to two general mechanisms polymeric release or substrate-mediated delivery (Figure 15.4). 

Cell culture substrate can also the influence gene delivery by affecting the occurrence of endocytosis and, thereby, the uptake of DNA-bound NPs by the cells. Hsu et al. [139] observed that the culture of MSCs on chitosan or HA-modified chitosan membranes increased the intracellular uptake of iron oxide NPs ( 5 nm) as well as naked DNA (3.3 kb, 5 mn) by more than fivefold. The increased internalization of NPs was associated with an increase in clathrin-mediated endocytosis on chitosan ( 50%) and in caveolae-mediated endocytosis on chitosan-HA ( 30-40%). In the case of naked DNA, but not iron oxide NPs, macropinocytosis also occurred on both substrates. 

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