Biomedical Engineering Reference
In-Depth Information
tures commonly applied in other protocols [86]. PLGA scaffolds fabricated
using this procedure proved useful as vehicles for sustained VEGF deliv-
ery [67, 78], and the VEGF was released in a bioactive form (Fig. 7) [78].
These scaffolds allow for delivery of multiple growth factors in the form of
recombinant proteins [67] or plasmid DNA [87].
As an alternative to solid vehicles, VEGF may be delivered from hydrogel-
based systems that exhibit structural similarity to the macromolecular-based
ECMofmanytissues[88].Importantly,thisphysicalformcantypicallybein-
troduced into the body using minimally invasive approaches (e.g., injection
with syringe). Synthetic materials currently used to form gels for VEGF de-
livery include derivatives of PEG and poly(acrylic acid) (PAA) [35, 89-92].
PEG hydrogels can be prepared by photopolymerization of macromers modi-
fied to contain reactive acrylate termini [89, 90] or via chemical reaction
of functionalized PEG macromers with thiol-containing substances [35, 91].
PAA hydrogels based on copolymers containing poly(
N
-isopropylacrylamide)
(PNIPAAm) are attractive VEGF delivery matrices because of their ther-
moresponsive gelling properties [92]. The lower critical solution temperature
(LCST) of PNIPAAm in water, defining the temperature above which gelation
occurs, is approximately 32
◦
C [92]. It can be adjusted to body temperature by
copolymerization in order to yield solutions which gel upon injection into the
body [88]. Despite offering suitable physical and chemical properties, these
synthetic materials may currently be limited in regard to their biocompatibil-
ity and biodegradability.
Naturally derived hydrogel forming polymers may provide highly bio-
compatible vehicles for VEGF delivery. ECM components isolated from tis-
sues and used for VEGF delivery include collagen, hyaluronic acid, and
fibrin [36, 93, 94]. Furthermore, chitosan derived from chitin of anthropod
exoskeletons has been used for VEGF delivery devices [95, 96]. Alginates rep-
Fig. 7 a
The cumulative release of VEGF from PLGA scaffolds fabricated by a gas foaming
particulate leaching technique.
b
The bioactivity of VEGF released from these matrices
at days 2, 7, and 14 was comparable to the effect obtained with known doses (5 and
20 ng
/
mL) of VEGF not incorporated into matrices (determined by an endothelial cell
proliferation assay) (J. Control. Release [78], with permission of Elsevier)
