Biomedical Engineering Reference
In-Depth Information
P3HB-18%4HB were essentially unchanged 26 weeks after implantation [263].
Summarizing the in vivo observations reported thus far it can be concluded
that P4HB has a resorption time of approximately 6-12 months, depending
on the sample morphology and implantation site. This corresponds approxi-
mately to the degradation time of PDLLA in vivo.
P3HB-4HB copolymers can be expected to degrade with a rate between
that of P4HB and P3HB. Thus for example, P3HB-10%4HB films have been
reported to degrade to 80% of the initial molecular weight (
M
n
)whenim-
planted for 4 months i.p. in rats [22] and P3HB-20%4HB films degraded to
55% of their initial
M
n
after 1 year of s.c. implantation in rats [192].
4.4
Applications in Tissue Engineering
P4HB and P3HB-4HB have primarily been tested as scaffolds in cardiovascu-
lar tissue engineering. Preliminary studies using heart valve scaffolds based
on PGA or P3HO-3HH showed limitations. While PGA has insufficient me-
chanical properties, P3HO-HH is resorbed too slowly [268] (see Sect. 6.4).
P4HB has been introduced as an alternative biomaterial with sufficient flexi-
bility and suitable degradation time for applications in the circulatory sys-
tem [47], and a large number of studies report on its potential for tissue
engineering of heart valves and small-caliber vascular grafts, as well as its
application as a patch material.
Heart Valves
Polymer heart valves made entirely from P4HB have been described, ei-
ther constructed from highly porous polymer films (Fig. 16a) [44] or made
by rapid prototyping. The latter allows for a resemblance of the human
anatomy, as derived from computed tomography of patients [269]. How-
ever, the majority of studies on P4HB-based heart valve scaffolds have used
a PGA/P4HB composite material made by dip-coating of a PGA mesh in
P4HB solution. Trileaflet heart valves fabricated from the PGA/P4HB com-
posite have been seeded with ovine carotid artery medial cells for 4 days
under static conditions, followed by addition of endothelial cells and culture
in a dynamic pulse duplicator for 14 days, and were implanted in sheep for
up to 20 weeks. Echocardiography demonstrated functioning leaflets with-
out stenosis, thrombus, or aneurysm. Complete degradation of the PGA mesh
was observed after 4 weeks, and that of the P4HB layer after 8 weeks. De-
spite this fast scaffold degradation, mechanical properties of the regenerated
valve leaflet tissue were comparable to those of native tissue at 20 weeks [43].
The remodeling process was followed by analysis of the cell phenotype
of the tissue-engineered construct after in vitro and in vivo testing. Cells
from in vitro constructs (14 days) were found to be activated myofibroblasts
with strong expression of
α
-actin and vimentin; cells from in vivo explants
