Anastomotic intimal hyperplasia and surface thrombogenicity are the main re
asons for the high failure rate of prosthetic small-diameter vascular graft
s. While anastomotic intimal hyperplasia is a multifactorial event, ongoing
surface thrombogenicity is primarily caused by the lack of an endothelium,
even after years of clinical implantation. After decades of poorly perform
ing synthetic artery-grafts, tissue engineering has emerged as a promising
approach to generate biologically functional bio-synthetic hybrid grafts mi
micking native arteries regarding the presence of an endothelial lining on
the blood surface. "In vitro endothelialization" represented the first gene
ration of such tissue-engineered vascular grafts, utilising cell culture te
chniques for the creation of a confluent autologous endothelium on ePTFE gr
afts. The clinical long-term results with this method in almost 200 patient
s are highly encouraging, showing patencies equal to vein grafts. Since "in
vitro endothelialization" requires cell culture facilities, it will always
be confined to large centres. Therefore, research of the 1990s turned to t
he development of spontaneously endothelializing implants, to make tissue-e
ngineered grafts amenable to the entire vascular-surgical community. Apart
from scaffold designs allowing transmural ingrowth, biological signalling t
hrough a facilitating ingrowth matrix holds a key to spontaneous endothelia
lization. In biological signalling, the increasingly deeper understanding o
f bio-active molecules and the discovery of domains and peptide sequences d
uring the 1980s created the expectation in the 1990s that peptide signallin
g may be all that is needed. This present review highlights the possible pr
oblems associated with such a reductionist approach. Using the fibronectin
molecule, we demonstrated that domains may be more suitable modules in tiss
ue engineering than peptide sequences. Anat Rec 263:379-387, 2001. (C) 2001
Wiley-Liss, Inc.