Biomedical Engineering Reference
In-Depth Information
medium chain-length PHA homopolymers (e.g., P3HO-3HH [58] or cross-
linked P3HU [50]) offer the advantage of having elastomeric properties. This
is of particular interest in tissue engineering applications since many tissues
in the body have elastomeric properties. For example, cardiovascular tissue
engineering requires a scaffold that can sustain and recover from cyclic de-
formations without irritation of the surrounding tissue. The development of
an elastomeric scaffold is therefore highly desirable. Moreover, mechanical
stimuli promote the formation of functional tissue, for example in cardio-
vascular or cartilage tissue engineering, and allow for gradual stress transfer
from the degrading synthetic matrix to the newly formed tissue. Most of the
biodegradable polyesters currently used in tissue engineering (such as PGA,
PDLLA, and their copolymers) undergo plastic deformation and fail when ex-
posed to long-term cyclic strain, thereby limiting their efficacy in engineering
elastomeric tissue [59].
3
Poly(3-hydroxybutyrate)
and Poly(3-hydroxybutyrate-
co
-3-hydroxyvalerate)
P3HB is the classic, most extensively studied and characterized PHA. It is
produced by a large number of microorganisms, including Gram-negative
and Gram-positive aerobic and photosynthetic species, lithotrophs or organ-
otrophs [18]. A glucose-utilizing mutant of
Alcaligenes eutrophus
can accu-
mulate up to 80% of P3HB with glucose as the carbon source. By addition of
propionic acid to the medium, P3HB-3HV is produced as a random copoly-
mer, with the comonomer ratio dependant on the ratio of propionic acid to
glucose. This technology has been scaled-up, and industrial processes for the
synthesis of large quantities of P3HB-3HV (Biopol) have been developed [60].
However, one of the major drawbacks for the broad utilization of P3HB or
P3HB-3HV in medicine is the limited supply of these polymers of medical
grade. Furthermore, there is currently no Drug Master File submitted to the
FDA, and a medical device made of P3HB or P3HB-3HV has not yet been
clinically approved.
3.1
Mechanical Properties
P3HB as a natural thermoplastic polyester has mechanical properties com-
parable with those of synthetically produced degradable polyesters such as
the polylactides [61]. The relatively high brittleness of the crystalline natu-
ral isotactic P3HB is of disadvantage in tissue engineering applications but
can be overcome by copolymerization and incorporation of PHA compo-
nents such as 3-hydroxyvalerate (3HV) [60], 4-hydroxybutyrate (4HB) [62], or
