HYBRID BIOMATERIALS FOR ENGINEERING VASCULAR TISSUES - Biologically-Responsive Hybrid Biomaterials - page 367

biocompatibility of the novel graft has been shown in a well-established porcine
model for arterial injury. In addition to performing in equal measure to state-of-
the-art bare metal stents for short-term application, the cRGD stent also exhibited
a significantly better long-term protection from neointimal hyperplasia. The
authors concluded that a 3-month observation in their porcine model was
comparable to data from 12-18 month follow-up in humans, which underscores
the possibility for good long-term efficacy of the grafts.
However, further in vivo studies with an extended follow-up period must be
undertaken to entirely survey the issue of long-term feasibility. In addition, the
transfer of the presented data to a human model is limited by the fact that the
animals lacked any spontaneous atherosclerosis. Thus, the observed beneficial
effects of the cRGD stent might be only representative for healthy arteries, as
mentioned by the authors themselves. In relation to vascular graft development
using biological peptides as opposed to vascular stents, the group of Seifalian
[29] has developed compliant poly(carbonate-urea)urethane (PCU) grafts
containing covalently bonded RGD-containing peptides. The authors
demonstrated that the addition of the RGD motif resulted in improved attachment
and differentiation of CD133 + cells, and may be more suitable for in situ
endothelialisation of vascular grafts in comparison to the naked PCU graft.
Although both of the aforementioned studies establish a very promising strategy,
the clinical potential of this approach is currently limited due to the fact that
integrins - the receptors ultimately interacting with the RGD peptide - are not
confined to EPCs, and hybrid materials need to be optimised to promote the
specific adhesion of EPCs only. The group of Patterson and colleagues have used
phage display screening methods to identify and select novel EPC-specific
peptide ligands with high specificity [30, 31]. The group identified the threonine-
proline-serine (TPS) motif as an important ligand binding to cell surface
receptors on human blood outgrowth endothelial cells (HBOEC). A subsequent
study employing a hybrid biomaterial consisting of TPS-peptide
(TPSLEQRTVYAK) immobilised to methacrylic terpolymers demonstrated
attachment of HBOEC, but not human umbilical vein endothelial cells
(HUVEC), appearing to show specificity for endothelial cells of progenitor
origin [31].
In situ endothelialisation of vascular grafts and stents composed of hybrid
biomaterials is a novel and exciting area of research that aims to eliminate the
need for surgical biopsies and extended in vitro culture protocols for producing
autologous endothelial cells that will render implanted grafts biocompatible.
Various peptides and techniques have been identified to promote endothelial cell