Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 58

cardiovascular devices. For example, macrophages cultured in the presence
of PET have been shown to release greater amounts of TGF- compared

with macrophages cultured in the absence of biomaterial (Greisler et al. ,
1996), a signifi cant observation as TGF-

β

may inhibit angiogenesis in vitro
(Baird and Durkin, 1986), and stimulates the recruitment of infl ammatory
cells in vivo .

β

3.2.5 Mesenchymal cell infi ltration

The infi ltration of SMCs, fi broblasts, and cardiomyocytes into implanted
devices promotes myointimal hyperplasia, which is a primary cause of
intermediate-term failures of cardiovascular interventions utilizing devices
such as stents, bypass conduits, and valves (Nikkari and Clowes, 1994;
Ramdev et al. , 2002; Klinkert et al. , 2003; McArthur et al. , 2003; de Mel
et al. , 2008). The intimal hyperplastic response and formation of plaques
are the pathologic consequences of the body's healing response to either
iatrogenic injuries to the established endothelium and vascular tissue
acquired during interventions or to implanted tissues which lack the
normal architecture of cardiovascular tissue (Bendeck et al. , 1994; Allaire
and Clowes, 1997; Boyle et al. , 1997; Hedin et al. , 1999; Nakatani et al. ,
2003). The injury response to angioplasty exemplifi es the pathogenesis of
intimal hyperplasia which is common to the process in all cardiovascular
implants. The response to injury starts early, with a conversion of a sub-
population of SMCs from a 'contractile' to a 'synthetic' phenotype during
the fi rst 24 hours after injury. These synthetically active SMCs demon-
strate an increased responsiveness to mitogenic and chemotactic factors
such as PDGF and FGF secreted in part by activated platelets and ECs,
and have increased ability to secrete their own growth factors when in the
active cell cycle (Sjolund et al. , 1990; Thyberg, 1996). These SMCs migrate
and proliferate, and invade from the arterial media to the disrupted intra-
luminal area of injury, which results in the formation of a 'neointima'
within the fi rst couple of weeks after injury.
Over the next several weeks to months, continued synthetic behavior by
SMCs contributes to the deposition of ECM proteins and further propaga-
tion and remodeling of the intraluminal myointimal lesion. After 2-3
months, in contrast to the earlier synthetic behavior, 'contractile' SMCs
may contribute to the restenotic process by inducing contractile properties
on the arterial wall, inducing further vessel narrowing leading ultimately to
an occlusive lesion (Zhang et al. , 1999). Thus, while the initial synthetic
response leads to the development and remodeling of the myointimal
lesion, both 'synthetic' and 'contractile' SMCs may contribute to the even-
tual interventional failure caused by myointimal hyperplasia, and proper
therapeutic interventions to attenuate this response need to take into

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