Biology Reference
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tion. The release rate is crucial as differentiation cues need to be released during
specific phases of differentiation. Surface-adsorbed drugs are released at rates that
are highly dependent on the strength of drug-surface interaction (by van der Waals,
electrostatic and covalent bonds), and the size of the surface area with which these
interactions can take place. In contrast, embedded drugs are typically released as the
implant degrades, although diffusion may play a minor role as well. To our knowl-
edge, no studies exist on delivery of miRNA from scaffolds; however, delivery of
siRNA from scaffolds has been carried out by various approaches [
6
] . These strate-
gies should be directly applicable to scaffold-directed miRNA delivery [
81
] .
Solid scaffolds containing embedded siRNA are typically prepared by adding
the siRNA during implant production. Two studies showed naked siRNA and
TransIT-TKO/siRNA vectors could be incorporated into electrospun fibres during
their production [
82,
83
]. Release rates were determined by the porosity of the
polymer surrounding the siRNA and the presence of a vector. Fibres releasing naked
siRNA and siRNA vectors induced different degrees of GAPDH silencing in
HEK293 cells (21 % and 31 %, respectively). The limited knockdown may reflect
damage to the siRNA or vector from exposure to organic solvents or mechanical
processing or limited release during the cell culture period. Interestingly, naked
siRNA demonstrated a knockdown despite the inherent barriers; possibly the scaf-
fold polymer polycaprolactone could act as a delivery vehicle as polycaprolactone
nanoparticles have previously been used to deliver siRNA successfully [
84
] . It has
also been demonstrated that siRNA-carrying micelles can be incorporated into
polyurethane foam scaffolds by mixing the dried vector powder with a scaffold
polymer prior to foaming, induced by the addition of lysine triisocyanate [
85
] .
Drugs that are adsorbed onto a scaffold are generally released faster than embed-
ded drugs [
86
]. One advantage of adsorbing drugs lies in the simpler methodology;
the miRNA can be added after scaffold production, enabling a laboratory to coat the
scaffold with their miRNA of interest without being involved in scaffold manufac-
turing. Since an adsorbed drug is added after implant production, it is not subjected
to potentially detrimental chemicals or processing during scaffold production.
Furthermore, miRNA can be coated onto commercial implants that are already
clinically approved. In one case, chitosan/siRNA nanoparticles targeting the
RHOA mRNA were adsorbed onto polymer filaments, where they could induce
RHOA silencing in neurons desensitising them to myelin inhibition of neurite
outgrowth [
87
] .
Hydrogels represent an interesting alternative to solid polymer sponges. They
can be loaded with siRNA vectors simply by mixing their components with the vec-
tor prior to gelling which, depending on the nature of the gelling component, makes
the process less damaging to the RNA and vector. In one study, alginate or collagen
was mixed with siRNA prior to CaCl
2
-, UV-radiation- or heating-induced gelling
[
88
]. The gels were subsequently found to silence a reporter gene in co-encapsu-
lated cells and cells growing beneath a hydrogel. Release rates were found to depend
on electrostatic interaction between vector and gel components. Finally, it was
shown that transfecting cells directly from a scaffold were much more efficient than
delivering a similar amount of siRNA through the medium.
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