HYBRID BIOMATERIALS FOR ENGINEERING VASCULAR TISSUES - Biologically-Responsive Hybrid Biomaterials - page 363

With regard to the cellular elements in vascular tissue engineering, many of
the current strategies are focused on the replacement/approximation of the
archetypal blood contacting surface - the vascular endothelium. The presence of
an endothelial lining in the small-calibre vascular graft is absolutely essential to
graft viability, as it inhibits thrombosis and contributes to long-term graft
patency. The endothelium can also control blood flow and vessel tone [8],
prevent infection and inflammation of the underlying graft wall, as well as
transmit mechanical and other signals to the underlying smooth muscle cells
(SMCs) [9, 10]. To form a functional endothelial monolayer, numerous attempts
have been made to coat the lumen of synthetic grafts with cultured endothelial
cells [11-13]. Such approaches demonstrated moderate improvement of graft
patency, but ultimately require implantation of a permanent foreign, non-
degradable structure. To develop tissue-engineered vascular grafts, endothelial
cells have been cultured together with SMCs on natural or synthetic
biodegradable polymer scaffolds, or self-assembled extracellular matrix (ECM)
[14-19]. The vascular grafts can subsequently undergo dynamic conditioning
protocols in vitro to enhance their mechanical properties prior to implantation.
However, there is still substantial loss of endothelial cells from the graft surfaces
under dynamic flow conditions. In addition, the production of vascular grafts in
this manner is a time-consuming and expensive process, while there are also
concerns for phenotypic alterations of endothelial cell populations after long
periods in vitro .
In addition to the development of small-calibre vascular grafts for restoring
normal blood flow to ischemic tissues, researchers in the vascular tissue
engineering field are investigating methods of generating intrinsic vasculature
within larger tissue constructs or within regenerating tissue (therapeutic
angiogenesis) [20-22]. The most critical hindrance to the clinical application of
implantable tissue-engineered grafts is the inability to sustain large numbers of
viable cells within a construct once implanted into the host. In vivo , most cells
within implanted tissue-engineered constructs do not survive distances of a few
hundred micrometers from the nearest capillary as the limits of oxygen diffusion
are exceeded, and such cells are dependent on neovascularisation to survive
within the construct. Equally, cells within ischemic tissues require therapeutic
intervention to restore or regenerate collateral vessels for tissue survival. Novel
strategies are being pursued to stimulate the body's natural mechanisms of blood
vessel formation for the treatment of myocardial ischemia and lower limb
ischemia by delivering angiogenic growth factors via hybrid biomaterials.