Ak. Tassiopoulos et Hp. Greisler, Angiogenic mechanisms of endothelialization of cardiovascular implants: a review of recent investigative strategies, J BIOM SC P, 11(11), 2000, pp. 1275-1284
Both cardiovascular implants and therapeutic interventions on native arteri
es fail due to biologic responses occurring at the blood/prosthesis/arteria
l wall and tissue/prosthesis/arterial wall interfaces, resulting in the fai
lure modes of thrombosis and myointimal hyperplasia. Systemic pharmacologic
approaches including use of anti-coagulant and anti-platelet agents have s
ignificant untoward side effects and have not resulted in a dramatic impact
on failure modes in many applications, including small diameter vascular g
rafts. Local delivery of therapeutic agents via surface attachment with def
ined release kinetics may alter thrombogenicity and/or myointimal hyperplas
ia. Therapeutic agents may include a spectrum of biologic agents from pepti
des to endothelial cells. Efficient attachment and release of these agents
in biologically active form is dependent upon improved methods of surface m
odification. The intended action of the biologic agent may similarly be imp
acted by the surface and bulk characteristics of the underlying biomaterial
.
It is often assumed, without concrete data, that surface re-endothelializat
ion may have a beneficial impact on both thrombogenicity acid myointimal hy
perplasia. New clinical data on endothelial cell seeding has been supportiv
e. Spontaneous re-endothelialization may be stimulated via an induced direc
ted angiogenesis resulting in trans-interstitial capillarization and surfac
e endothelialization. Recent advances in therapeutic angiogenesis have sugg
ested the power of angiogenic factors to induce neovascularization of ische
mic tissue beds. These concepts have been used to surface modify prosthetic
devices with either VEGF or FGF and both in vitro and animal data suggest
a potent stimulation of surface re-endothelialization. Neither of these gro
wth factors is likely to be ideal. VEGF is relatively endothelial cell spec
ific but is a relatively weak endothelial cell mitogen. FGF-I and FGF-2 are
more potent mitogens but are less cell specific. Recent work has led to th
e generation of mutant growth Factors via site-induced mutagenesis and resu
lts of several such FGF mutants on endothelial cell and smooth muscle cell
proliferative response have been studied. The use of 'designer growth facto
rs' on cardiovascular implants and on manipulated native vessels may have a
significant positive impact on re-endothelialization and thereby on the fa
ilure modes of thrombosis and myointimal hyperplasia.