Biomedical Engineering Reference
In-Depth Information
Table 1 Equilibrium binding constants (K
A
) calculated from the interactions of alginate-sulfate
with proteins (SPR analysis) [
76
,
77
]
K
A
(M
-1
)
Protein
2.80 9 10
7
Acidic fibroblast growth factor
2.57 9 10
6
Basic fibroblast growth factor
9.93 9 10
6
Epidermal growth factor
5.36 9 10
7
Hepatocyte growth factor
1.01 9 10
8
Insulin-like growth factor-1
1.38 9 10
7
Interleukin-6
3.53 9 10
7
Platelet-derived growth factor-BB
2.06 9 10
8
Stromal cell derived factor-1
6.63 9 10
7
Transforming growth factor-b1
1.81 9 10
6
Thrombopoietin
6.98 9 10
6
Vascular endothelial growth factor
the alginate as cell vehicle [
76
,
83
]. For example, affinity-binding alginate scaf-
folds were shown to control the release of three known angiogenic factors, PDGF-
BB, TGFb1 and VEGF. In vitro release studies revealed a sequential order of
protein release from the scaffold, as predicted by the values of the equilibrium
binding constants to alginate-sulfate (see Table
1
) and their initial concentrations:
VEGF was released first, followed by PDGF-BB and TGFb1. The sequential
delivery of factors from the affinity-binding scaffold mimicked the signal cascade
acting in angiogenesis. By contrast, factor release from the scaffolds lacking
alginate-sulfate was rapid and was governed mainly by a burst effect. Subcuta-
neous implantation of triple-factor bound scaffolds resulted in superior vascular-
ization, compared to factor-adsorbed or untreated scaffolds [
76
].
The affinity-binding alginate scaffolds were also used for the creation of a
vascularized cardiac patch [
70
]. Such scaffolds containing a cocktail of pro-sur-
vival and angiogenic factors [insulin growth factor-1 (IGF-1), stromal cell-derived
factor-1 (SDF-1) and VEGF] were seeded with rat neonatal cardiomyocytes, and
then transplanted onto the omentum to achieve host-induced vascularization of the
patch. Seven days later, the resultant vascularized patches were harvested and
re-transplanted to replace the scar tissues of the infarcted rat hearts. The pre-
vascularization within the affinity-binding patch was proven to significantly improve
the therapeutic outcome, as judged by the structural and electrical integration into
the scar tissue four weeks post-transplantation onto an infarcted heart. Moreover, the
pre-vascularized cardiac patch was able to attenuate the deterioration of cardiac
function, indicated by echocardiography and electrophysiology analyses [
70
].
In another study, the sequential delivery of IGF-1 and hepatocyte growth factor
(HGF) from injectable affinity-binding alginate hydrogel was shown to promote
myocardial repair in a similar rat model of acute myocardial infarction. The dual
delivery of IGF-1 and HGF from affinity-binding alginate biomaterial was able to
preserve scar thickness, attenuate infarct expansion and reduce scar fibrosis after 4
weeks, concomitantly with increased angiogenesis and mature blood vessel for-
mation at the infarct. Furthermore, this treatment prevented cell apoptosis and
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