Biomedical Engineering Reference
In-Depth Information
6.4
Applications in Tissue Engineering
Heart Valves
Initial studies have shown that biodegradable scaffolds made of polyglactin/
PGA mesh composites seeded with autologous vascular cells can be implanted
to replace a single pulmonary valve leaflet in a lamb model [285]. However,
attempts to construct a trileaflet heart valve scaffold failed due to stiffness
of the materials [41]. In subsequent studies, P3HO-3HH was introduced as
an elastomeric polymer to generate scaffolds with appropriate mechanical
properties. These constructs first had a multilayered structure. The conduit
wall consisted of a highly porous PGA mesh on the inside connected to
a nonporous P3HO-3HH film on the outside. The valve leaflets had a PGA-
(P3HO-3HH)-PGA sandwich structure with a P3HO-3HH nonporous film
covered by a layer of PGA mesh on each side. The PGA mesh was chosen as
a porous matrix for cell seeding and growth, while the P3HO-3HH layer pro-
vides flexibility and mechanical strength. These scaffolds were tested in vitro
for cell attachment under pulsatile flow conditions [41]. However, the PGA-
(P3HO-3HH)-PGA sandwich combination failed in vivo because of thrombus
formation and lack of good tissue formation [268].
Modified constructs, consisting of the PGA-(P3HO-3HH)-PGA conduit
and leaflets made from porous P3HO-3HH films were seeded with autolo-
gous vascular cells and implanted to replace the pulmonary valve and main
pulmonary artery for up to 24 weeks in sheep. Postoperative examination of
the preseeded scaffolds showed the formation of viable tissue without throm-
bus formation, while unseeded controls developed thrombi on all leaflets after
4 weeks. However, it was concluded that P3HO-3HH, due to the slow resorp-
tion, is not the ideal polymer for heart valve scaffolds [268]. The remodeling
kinetics of these scaffolds after implantation have also been analyzed. While
both the elastin and proteoglycans/glycosaminoglycans levels were compa-
rable to those found in natural tissue within the 24-week period, there was
a continuous increase in production and deposition of collagen. This might
have been caused by a suboptimal matrix regulation, a pathologic collagen
production, or both. Such pathologic matrix remodelling with excessive ECM
deposition is not only a common problem after vascular injury but also one of
the limiting factors for tissue engineering strategies to replace small-caliber
vascular grafts [286].
Heart valve scaffolds with conduit and leaflets made entirely from P3HO-
3HH porous films [287] were tested in vitro under static and pulsatile flow cell
culture conditions [44, 281]. A larger number of vascular cells, together with
the formation of an oriented and confluent cell layer, was found on scaffolds
exposed to pulsatile flow [281]. The P3HO-3HH heart valves, preseeded with
vascular cells under static conditions, were tested for up to 17 weeks in the
pulmonary position in a lamb model. The valves showed good functionality
