Biomedical Engineering Reference
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(16-20 weeks) were fibroblast-like, with expression of vimentin but unde-
tectable levels of
-actin, which is similar to the native valve. The ECM
architecture of the explanted tissue resembled that of native valves. However,
leaflets were only partially covered with endothelial cells [252].
Other cell types investigated for preseeding of PGA/P4HB heart valve
scaffolds include marrow stromal cells (MSCs), which exhibit the potential
to differentiate into multiple cell-lineages and can be easily obtained clini-
cally [255-257]. Ovine aortic valvular endothelial cells and circulating en-
dothelial progenitor cells seeded on PGA/P4HB proliferate in response to
vascular endothelial growth factor and transdifferentiate to a mesenchymal
phenotype in response to transforming growth factor
α
1, which is a critical
step during embryonic development of cardiac valves [254]. Furthermore, hu-
man pediatric aortic cells and factors influencing their maturation have been
studied using PGA/P4HB scaffolds [258].
A number of studies based on PGA/P4HB have confirmed the importance
of dynamic cell culture conditions that reproduce physiological mechanical
stress and of pulsatile flow to achieve optimally functional scaffolds [43, 45,
46, 255, 259]. A bioreactor that includes dynamic flexure as a major mode of
deformation in the native heart valve cusp has been tested on PGA/P4HB and
PLLA/P4HB composite scaffolds [270].
A combination of an acellular porcine heart valve coated with P3HB, P4HB,
or P3HB-4HB has recently been developed (Fig. 16b) [51]. The decellularized
heart valve resembles the natural 3D structure of the heart valve, providing
nearly ideal flow conditions. It is composed mainly of collagen, elastin, and
proteoglycans, and contains protein ligands for cell attachment and receptor
activation. The protein/polyester combination has been developed to over-
come limitations of protein and polymer valves alone. Polymer coating of
a tissue-derived acellular scaffold can improve the mechanical stability and
β
Fig. 16 a Trileaflet heart valve scaffold fabricated from porous P4HB [44] (reprinted by
permission of Lippincott Williams & Wilkins). b Decellularized porcine heart valve as 3D
matrix for P3HB, P4HB, or P3HB-4HB coating [51]
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