Biomedical Engineering Reference
In-Depth Information
integrate with the host tissues, they may be replaced
in vivo
in a timely fashion by native constructs
built by the cells seeded into them. It has been widely accepted that an ideal tissue-engineered bone
substitute should be a synthetic scaffold, which is biocompatible and provides for cell attachment,
proliferation and maturation, has mechanical properties to match those of the tissues at the site of
implantation, and degrades at rates to match tissue replacement. Table 1.6 lists selected properties
of synthetic, biocompatible, and biodegradable polymers that have been intensively investigated as
scaffold materials for tissue engineering, type I collagen i bers being included for comparison.
1.3.5.1
Bulk Degradable Polymers
1.3.5.1.1
Saturated Poly-
α
-Hydroxyesters (PLA, PGA, and PCL)
The biodegradable synthetic polymers most often utilized for 3-D scaffolds in tissue engineer-
ing are the poly(α-hydroxyacids), including poly(lactic acid) (PLA) and poly(glycolic acid) (PGA),
as well as poly(lactic-
co
-glycolide) (PLGA) copolymers [91]. PLA exists in three forms: l-PLA
(PLLA), d-PLA (PDLA), and racemic mixture of d,l-PLA (PDLLA).
These polymers are popular for various reasons, among which biocompatibility and biode-
gradability stand out. These materials have chemical properties that allow hydrolytic degradation
through de-esterifi cation. After the process of degradation is over, the monomeric components of
each polymer are removed through natural pathways: PGA can be converted to other metabolites
or eliminated by other mechanisms, and PLA can be cleared through tricarboxylic acid cycle. The
body already contains highly regulated mechanisms for completely removing monomeric compo-
nents of lactic and glycolic acids. Due to these properties, PLA and PGA have been used in products
such as degradable sutures and have been approved by the U.S. Food and Drug Administration
(FDA) [28]. Other signifi cant properties of these polymers are their very good processability, and
their ability to exhibit a wide range of degradation rates, physical, mechanical, and other proper-
ties, which can be achieved by PLA and PGA of various molecular weights and their copolymers.
However, these polymers undergo a bulk erosion process in contact with body fl uids such that they
can cause scaffolds to fail prematurely. In addition, abrupt release of these acidic degradation prod-
ucts can cause a strong infl ammatory response [92,93].
In general, PGA degrades faster than PLA, as listed in Table 1.6. Their degradation rates
decrease in the following order.
PGA
>
PDLLA
>
PLLA
Degradation rates decrease
Table 1.6 also lists the mechanical properties of type I collagen, which is the major organic
component of ECM in bone. The strength and ductility (e.g., ultimate elongation) of PLA and PGA
are comparable to those of type I collagen i bers.
PDLLA has been extensively investigated as a biomedical coating material because of its excel-
lent features with respect to implant surface [28,104]. In addition to its high mechanical stabil-
ity [105], PDLLA also shows excellent biocompatibility
in vivo
and good osteoinductive potential
[106]. PDLLA of low molecular weight can be combined with drugs like growth factors [106],
antibiotics [107], or thrombin inhibitors [108] to establish a locally acting drug-delivery system. It
is due to these desirable features that much more attention has recently been paid to PDLLA for
applying it as a scaffold material for tissue engineering.
Highly porous 3-D scaffolds made of Bioglass-fi lled PDLLA and PLGA were fabricated by
Boccaccini et al. [59]. Since then an increasing number of publications have emerged on this subject,
as reviewed recently [12]. Porous PDLLA foams and Bioglass-fi lled PDLLA composite foams have
both been fabricated, using thermally induced-phase separation (TIPS) technique [109,110]. Bioglass-
fi lled PDLLA composite foams exhibit high bioactivity, assessed by the formation of hydroxyapatite
