Biomedical Engineering Reference
In-Depth Information
with extracts prepared at 37
°
C caused slight stimulation of mitochondrial activity and cells incu-
C media revealed a concentration-dependent decrease of mitochondrial activity.
These
in vitro
results suggested that PLDLA and PLGA have satisfactory biocompatibility; how-
ever, high concentrations of the degradation products were reported to show a toxic infl uence on
the cell culture systems used.
25
Adverse tissue response in PLA implants have been reported to be
lower than PGA and foreign body response to PLLA would usually take longer
in vivo
. The crystal-
line debris yielded during degradation may be responsible for foreign body response and osteolysis,
which are sometimes observed with PLLA.
26
Adverse infl ammatory reactions in the long term have
been known to occur with the use of slowly degrading bioabsorbable poly-l-lactide screws for bone
fi xation.
27
Complications from implants of lactide and glycolide occur typically at a rate of less than
10%. PCL is currently regarded as a nontoxic and tissue-compatible material
28
with good cell inter-
action in cell culture studies.
29
Thus, designing of devices for any biomedical application necessi-
tates the tailoring of polymers to suit the physical, mechanical, and biological requirements.
10,30
bated with the 70
°
15.2.1.2 Poly(
ε
-Caprolactone)
PCL is derived by the ring opening polymerization of ε-caprolactone (Figure 15.4). It is a degradable
polyester with a low melting point (~60
C. PCL is a
hydrophobic, semicrystalline polymer, and has a relatively slow rate of degradation. PCL undergoes
hydrolytic degradation and is assisted by enzymatic degradative processes. The molecular weight
of the polymer infl uences especially the fi rst stages of the degradation wherein random hydrolytic
ester cleavage occurs autocatalyzed by the carboxyl end groups. The second stage of degradation
sets in when the molecular weights are low and oligomers begin diffusing through the bulk matrix,
at which point, fragmentation occurs.
31,32
PCL has been studied for drug delivery applications and is especially compatible with hydro-
phobic drug entities, and high loading of the drug can be achieved. It has also been developed as a
wound closure staples.
33
°
C) and a glass transition temperature (
T
g
) of
-
60
°
15.2.1.3
Copolymers of PLA, PGA, and PCL
Copolymers based on PLA, PGA, PCL, and PEG confer a wide range of properties to polymers
and thus open up new avenues for drug delivery, gene therapy, orthopedic implants, scaffolds for
tissue engineering, and many other biomedical applications. The copolymers can be tailored to
impart different crystallinity, morphology, molecular weight, thermal, and mechanical properties;
thus the biodegradability can be controlled according to the clinical need. In order to alter, for
example, the mechanical properties and degradation characteristics of polymers, copolymers can be
fabricated. There is no linear relationship between the physical properties of the source homopoly-
mers and the resulting copolymers.
34
The crystallinity of copolymers are lower than their related
homopolymers, thus degrade more rapidly. For instance, the copolymer of PLLA and PGA with a
ratio of 25:70 mol% of glycolide is largely amorphous and thus degrades more rapidly than PLLA
itself. If PDLLA is a component of the PGA/PLA copolymer, the copolymer itself is amorphous
in nature. The sequence of the component units in a copolymer linear chain also affects degrada-
tion rate. Thus block and random copolymers exhibit different degradation rates. Biodegradable
polymers such as PLA and PGA are used extensively as scaffolds in tissue engineering for the
regeneration of musculoskeletal tissues.
35,36
Copolymers and homopolymers can be fabricated into
different sizes and shapes with differing molecular architecture and each of these parameters infl u-
ence the degradation kinetics. Thus,
in vitro
degradation studies need to consider the effects of
composition, porosity,
37
permeability, mechanical loading, and the effect of a dynamic fl ow medium
experienced
in vivo
.
38
The aliphatic polyesters are one of the most attractive groups of polymers that have been widely
used in biomedical applications. The advent of the degradable suture using PLA, PGA, PCL, or
