HYBRID BIOMATERIALS FOR ENGINEERING VASCULAR TISSUES - Biologically-Responsive Hybrid Biomaterials - page 366

2.1. EPC capture using cRGD peptides
Cell adhesion molecules or ligands impart a level of signaling that controls the
regulation of gene expression and cellular organization. Bioactivity of a synthetic
polymer scaffold can be modified with covalently-attached adhesion peptide
sequences, such as arginine-glycine-aspartic acid (RGD) or tyrosine-isoleucine-
glycine-serine-arginine (YIGSR) [44]. Such sequences are present on a number
of ECM proteins, forming a physical link between the ECM and the cells via
integrin cell surface receptors [45]. Incorporated sequences function to improve
cell adhesion, spreading and more sophisticated functions, whilst also enabling
integrin-mediated activation of a number of cell signaling pathways that are
critical to tissue development and remodeling [46]. Previous published data has
demonstrated the expression of integrins with binding motifs for cyclic RGD
(cRGD) on EPCs [47, 48], and it is thought that homing and differentiation of
EPCs are largely dependent on integrin binding and the resulting signaling
cascade that is triggered [49]. Therefore, coating of biomaterials by EPC
attracting peptides such as cRGD may be useful for endothelialization of
synthetic surfaces by EPCs.
Blindt and colleagues recently described a novel stent coating loaded with
integrin-binding cRGD peptide (GPenGRGDSPCA) [28]. The cyclic structure of
the peptide is believed to more closely approximate the conformation of the
natural ligand, and was established by a disulfide bond between penicillamine
(Pen) and cysteine. The authors hypothesized that EPCs would be attracted and
bound to the stent because they express specific integrins that have high affinity
for the RGD sequence. Through in vitro and in vivo porcine studies, the authors
demonstrated that the cRGD peptides embedded in the coating of the stainless
steel stent promoted stimulation of cell outgrowth and shear-resistant attachment
of EPCs to the stent, as well as acting as chemoattractants for EPCs. Effective re-
endothelialisation was achieved comprising labelled infused porcine EPCs as
well as endogenous CD34 + cells. Subsequent analyses for vessel occlusion in
vivo revealed that there was no significant beneficial effect of the cRGD stent at
4 weeks after implantation. However, after 12 weeks, the mean neointimal area
in the cRGD-loaded stent was significantly lower (2.2 ± 0.3 mm 2 ) compared to
the unloaded (3.8 ± 0.4 mm 2 ) or bare metal stent (3.8 ± 0.3 mm 2 ). Additionally,
the cross-sectional area of stenosis was significantly lower with the cRGD-
loaded stent (33 ± 5 %) in comparison with the controls - unloaded (54 ± 6 %)
and bare metal stent (53 ± 3 %), respectively.
In this study [28], Blindt and colleagues demonstrated proof of concept for
their innovative approach of a cRGD-loaded stent coating. The feasibility and