HYBRID BIOMATERIALS FOR ENGINEERING VASCULAR TISSUES - Biologically-Responsive Hybrid Biomaterials - page 364

Based on the current literature, this topic chapter focuses on two exciting
applications of hybrid biomaterials for the restoration of blood flow to damaged
tissues. The first application is the recruitment of autologous endothelial
progenitor cells (EPCs) to vascular grafts or stents composed of hybrid
biomaterials. The second application is the development of a tissue
microvasculature subsequent to ischemia, or for the purpose of developing large
volume, implantable tissue-engineered structures.
2. Endothelialisation of Vascular Prostheses
The need to produce thrombo-resistant small-calibre vascular grafts for clinical
application led to the innovative use of endothelial cells to pre-coat the graft
lumen prior to implantation [11-13]. The majority of research on the promotion
of endothelial cell seeding on vascular structures has involved coating the
luminal graft surface with individual ECM proteins or protein mixtures [23, 24].
Such surface treatments have enhanced cellular retention on synthetic structures
but there still remains a need for improved materials or adhesion factors that
improve cell attachment and prevent subsequent cell loss under flow conditions
[25]. Further drawbacks of this approach include the fact that autologous
endothelial cells are a requirement for successful application of this technique
due to the immunological concerns presented by donor endothelial cells [7]. As a
result, an intact vessel must be harvested from another site in the patient in a
prior surgical procedure in order that healthy endothelial cells can be isolated for
subsequent seeding on the replacement graft. In addition, the currently used
synthetic fabric grafts composed of Dacron™ or ePTFE cannot be remodelled by
the patient's cells. Poor compliance together with an inability to remodel can
prevent long-term adaptation of the vessel within the implantation site, which
may ultimately lead to occlusion by intimal hyperplasia [7].
These limitations have driven intense research into the development of
alternative graft materials and identification of more suitable endothelial cell
sources. Graft material properties can be modified through hybridisation or
biofunctionalisation to more closely approximate the ECM and promote
desirable protein and cellular interactions. The ECM acts not only as a structural
scaffold material but also contains a myriad cell signalling motifs and growth
factors that guide cell attachment and cellular responses [26]. The environment in
the immediate vicinity of the cell provides defined structural cues that determine
cell-specific behaviour, including attachment, proliferation, differentiation, and
the protein synthesis needed for tissue organisation and remodeling. Structural