Biomedical Engineering Reference
In-Depth Information
considered to be advantageous. Both
in vitro
toxicity and
in vivo
nonspecific foreign body reactions like
sterile sinuses have been reported in orthopedic implants made from PGA and/or PLLA (Eitenmuller
et al., 1989; Bostman et al., 1990; Daniels et al., 1992; Hofmann, 1992; Winet and Hollinger, 1993).
Several investigators indicated that the glycolic or lactic-acid rich-degradation products have the
potential to significantly lower the local pH in a closed and less body-fluid buffered regions sur-
rounded by bone (Sugnuma et al., 1992). This is particularly true if the degradation process proceeds
with a burst mode (i.e., a sudden and rapid release of degradation products). This acidity tends to
cause abnormal bone resorption and/or demineralization. The resulting environment may be cyto-
toxic (Daniels et al., 1992). Indeed, inflammatory foreign body reactions with a discharging sinus
and osteolytic foci visible on x-ray have been encountered in clinical studies (Eitenmuller et al.,
1989). Hollinger et al. recently confirmed the problem associated with PGA and/or PLLA orthope-
dic implants (Winet and Hollinger, 1993). A rapid degradation of a 50:50 ratio of glycolide−lactide
copolymer in bone chambers of rabbit tibias has been found to inhibit bone regeneration. However,
emphasis has been placed on the fact that extrapolation of
in vitro
toxicity to
in vivo
biocompatibility
must consider microcirculatory capacity. The increase in the local acidity due to a faster accumula-
tion of the highly acidic degradation products is also known to lead to an accelerated acid-catalyzed
hydrolysis in the immediate vicinity of the biodegradable device. This acceleration in hydrolysis
could lead to a faster loss of mechanical property of the device than we expect. This finding sug-
gests the need to use components in totally biodegradable composites so that degradation products
with less acidity would be released into the surrounding area. A controlled slow release rather than a
burst release of degradation products at a level that the surrounding tissue could timely metabolize
them would also be helpful in dealing with the acidity problem. Copolymers of composition ratio of
10DMTMC/90LLA or 10TMC/90LLA appear to be a promising absorbable orthopedic device. Other
applications of this type of copolymers include nerve growth conduits, tendon prostheses, and coat-
ing materials for biodegradable devices.
Another unique example of l-lactide copolymer is the copolymer of l-lactide and 3-(
S
)[(a l k ylox y-
carbonyl) methyl]-1,4-dioxane-2,5-dione, a cyclic diester (Kimura, 1993). The most unique aspect of
this new biodegradable copolymer is the carboxyl acid pendant group which obviously would make the
new polymer not only more hydrophilic and hence faster biodegradation, but also more reactive toward
future chemical modification through the pendant carboxyl group. The availability of these carboxyl-
reactive pendant sites could be used to chemically bond antimicrobial agents or other biochemicals like
growth factors for making future wound closure biomaterials having new and important biological
functions. Unfortunately, there are no reported data to evaluate the performance of this new absorbable
polymer for biomedical engineering use up to now.
Block copolymers of PLLA with poly(amino acids) have also been reported as a potential con-
trolled drug-delivery system (Nathan and Kohn, 1994). This class of copolymers consists of both ester
and amide linkages in the backbone molecules and is sometimes referred as poly(depsipeptides) or
poly(esters-amides). Poly(depsipeptides) could also be synthesized from ring-opening polymerization
of morpholine-2,5-dione and its derivatives (Helder et al., 1986). Barrows has also made a series of
nonamino acid-based poly(ester-amides) from polyesterification of diols that contain preformed amide
linkages, such as amidediols (Barrows, 1994).
The introduction of poly(ethylene oxide) (PEO) into PLLA in order to modulate the hydrophilicity
and degradability of PLLA for drug control/release biomaterials has been reported and an example is
the triblock copolymer of PLA/PEO/PLA (Li et al., 1998). Biomaterials having an appropriate PLLA and
PEO block length were found to have a hydrogel property that could deliver hydrophilic drugs as well as
hydrophobic ones such as steroids and hormones. Another unique biodegradable biomaterial consisting
of a star-block copolymer of PLLA, PGA, and PEO was also reported for protein drug-delivery devices
(Li and Kissel, 1998). This star-shaped copolymer has four or eight arms made of PEO, PLLA, and PGA.
The glass transition temperature and the crystallinity of this star-shaped block copolymer were signifi-
cantly lower than the corresponding linear PLLA and PGA.
