Biomedical Engineering Reference
In-Depth Information
It was not until the 1980s that P3HB again became of interest for biomedical
research when P3HB tablets for sustained drug delivery were studied [27-29].
Since that time, an increasing number of investigations on the clinical potential
of P3HB have been reported, including as implants for bone repair [30], anas-
tomoses tubes and separating films [31], as well as cardiovascular patches [32].
These pericardial patches have subsequently been tested in humans, making
this the first reported clinical study of P3HB implants [33]. P3HB conduits and
scaffolds have been introduced for the repair of peripheral nerves [34-36] and
spinal cord [37], and P3HB patches have been developed for covering damaged
tissue of the gastrointestinal tract [38] or injured dura mater [39]. Summarizing
these studies, P3HB can be considered to be a polymer with high potential as
a degradable implant material [13, 16, 17].
Thus far, the majority of research on medical applications of PHAs refers
to P3HB and its copolymer poly(3-hydroxybutyrate-
co
-3-hydroxyvalerate),
P3HB-3HV. However, due to their broad range of mechanical and biodegra-
dation properties, other PHAs have been drawing increasing attention
for biomedical applications, particularly in cardiovascular tissue engineer-
ing. Initially, elastomeric poly(3-hydroxyoctanoate-
co
-3-hydroxyhexanoate),
P3HO-3HH, was used to develop scaffolds for repair of blood vessels [40]
and heart valves [41]. Subsequently, poly(4-hydroxybutyrate), P4HB, was in-
troduced as a faster degrading alternative to P3HO-3HH and was tested as
vascular patches [42], heart valves [43, 44], and vascular grafts [45, 46]. Based
on results from these studies, P4HB is regarded as a particularly promis-
ing polymer for clinical applications [47]. Furthermore, copolymers such
as poly(3-hydroxybutyrate-
co
-4-hydroxybutyrate), P3HB-4HB, and poly(3-
hydroxybutyrate-
co
-3-hydroxyhexanoate), P3HB-3HH, have been introduced
as scaffolds for tissue engineering, including the repair of cartilage and
bone [48, 49]. An example of an unsaturated PHA is PEG-grafted poly(3-
hydroxyundecenoate) (P3HU, containing 3-hydroxynonenoate and other
unsaturated and saturated side-chains of medium length), which has been
suggested as a suitable material for applications in blood contact [50]. The
chemical structures of PHAs reviewed in this article are shown in Fig. 2.
The range of properties provided by PHAs is exemplified in Fig. 3 [38,
51-56]. The high crystallinity of the isotactic P3HB leads to stiffness and
brittleness, as well as slow hydrolysis in vitro and in vivo. P4HB films are
characterized by low stiffness and high elongation at break. The low de-
gree of crystallinity accelerates the in vitro degradation. Interestingly, in vivo
degradation of P4HB involves a surface erosion mechanism. P3HO-3HH is an
elastomer with a low crystallinity, leading to faster in vitro degradation than
P3HB despite the increased hydrophobicity resulting from the longer alkyl
side-chains. However, the degradation of P3HO-3HH appears to be slowed
down under in vivo conditions.
P3HB copolymers containing more than 20% of 4-hydroxybutyrate [47]
or medium chain-length (C6-18) 3-hydroxyalkanoate units [57], as well as
