Biomedical Engineering Reference
In-Depth Information
blood cells, which may otherwise mediate clotting and vessel occlusion [61].
As outlined above, protein adsorption is critical to cellular adhesion and,
therefore, PEG has been widely studied for its role in decreasing protein and
unspecific cell adhesion [47, 62]. A variety of approaches has been developed
to attach PEG to polymer surfaces. For example, synthesis of PEG containing
copolymers and covalent grafting of PEG to surfaces that were functionalized
with reactive silanol groups proved useful to decrease both protein adsorp-
tion and cell attachment [63-65]. Since the nonfouling properties of PEG are
dependent on the surface chain density, alternative approaches using plasma
deposition of tetraglyme to prepare highly cross-linked PEG-like surfaces
have been explored [65].
3.1.3
Multiple Growth Factor Signaling
In the body, VEGF acts in a well-concerted interplay with various other
growth factors, and the adequate mimicry of these simultaneous and se-
quential interactions may be essential to regenerate functional tissues. Sim-
ultaneous interactions occur, for example, between VEGF and bFGF during
initiation of blood vessel formation [18, 19], and may be recreated by simply
incorporating the different proteins into the same polymer delivery system.
The utility of this general concept has earlier been demonstrated in the con-
text of bone regeneration and blood vessel formation with growth factor
combinations that did not involve VEGF [57, 66]. For example, simultaneous
delivery of bone morphogenetic protein-2 (BMP-2) and TGF-beta improved
bone formation relative to the individual delivery of either growth factor [57].
Sequential delivery of growth factors has been realized with composite
systems that are composed of multiple polymer phases with distinct release
kinetics [67, 68]. The growth factor(s) acting early during regeneration are
typically incorporated into a rapidly releasing phase, whereas the growth fac-
tor(s) signaling later in the process are loaded in a phase with more sustained
release characteristics. This approach has been applied in the context of ther-
apeutic angiogenesis for sequential delivery of VEGF and PDGF from poly
(lactic-co-glycolic acid) (PLGA) scaffolds [67]. This specific system was de-
signed to release the two growth factors with differential kinetics by mixing
polymer microspheres containing pre-encapsulated PDGF with lyophilized
VEGF before processing into scaffolds. Since VEGF largely associates with the
surface of the scaffold it is subject to rapid release. In contrast, the PDGF in-
corporation approach results in a more even distribution of factor throughout
the matrix, with release regulated by the degradation of the polymer used to
form microspheres. In a different approach, sequential delivery of growth fac-
tors has been achieved by the development of composite systems consisting
of gelatin microspheres incorporated into a synthetic hydrogel matrix (oligo
[poly (ethylene glycol) fumarate]) [68].
 
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