Biomedical Engineering Reference
In-Depth Information
associated with a decrease in mass, while the
volume of the construct stays the same. This
results in a decrease in density and mechanical
strength.
One concern with bulk degradation is a phe-
nomenon known as the autocatalytic effect
[
harm to the host, it may be considered biocom-
patible. Material intended for implantation
should be such as to minimize the intensity and
duration of the response.
The tissue response to an implanted scaffold
involves three stages [
84
]. Stage
1
occurs during
]. This often occurs with synthetic polymers
whose degradation products are acidic. When
degradation occurs, the interior degradation
products cannot diffuse through the polymer
network. This causes a local increase in acidity,
which in turn causes a more rapid degradation
resulting from hydrolysis of labile linkages.
Surface degradation is similar to soap dis-
solution. The material degrades at the surface
at a constant rate. This causes the construct to
thin out, yet bulk integrity and structure are
maintained. Surface degradation is common
with polyanhydrides and polyorthoesters,
which, though hydrophobic, are highly suscep-
tible to hydrolysis and degrade at the surface.
As the material degrades, the size of the con-
struct decreases as mass is lost, but the density
remains unchanged. This feature allows the
polymer to maintain mechanical integrity, a
property critical for bone tissue engineering.
The preferred method of degradation is a
function of the engineering requirements, the
host tissue, and the need for mechanical integ-
rity. The speed at which a scaffold degrades can
be arrived at by varying the properties of the
polymer. For example, a material with more
hydrophilic monomers and acidic end groups
and a more hydrolytically reactive backbone,
less crystallinity, and smaller size would tend
to have a higher degradation rate [
55
the fi rst
weeks after implantation and is
characterized by acute and chronic infl amma-
tory responses. Acute infl ammation generally
lasts minutes to days and depends on the extent
of the injury [
1
to
2
]. Chronic infl ammation results
from the long-term presence of infl ammatory
stimuli and is confi ned to the implantation site.
In general, the stage
3
response is independent
of the degradation rate of the polymer [
1
84
].
Stage
begins as the numbers of monocytes
and macrophages increase. In stage
2
, fi brous
encapsulation of the foreign material is initi-
ated. In contrast to stage
2
1
, the length of stage
2
is a function of the rate of biodegradation of
the scaffold [
84
]. Fibrous encapsulation contin-
ues in stage
. The length of this stage depends
on the degradation rate of the polymer. Slowly
degrading polymers have a stage
3
response
that lasts weeks to months, whereas with rapidly
degrading polymers, stage
3
3
can be as short as
1
].
The immune response is of major concern in
bone tissue engineering, because degradation
products cause failure in many orthopedic
implants [
to
2
weeks [
84
93
]. Degradation products less than
20
ยต
m in diameter can be phagocytosed by
macrophages [
]. Degradation particles act on
bone cells indirectly through the secretory
products of macrophages that are drawn to
the area from the immune response [
93
]. The site
of the implant can also affect degradation. In a
poorly vascularized area with low diffusion,
degradation products will tend to remain
longer, causing a rise in acidity. This is a situa-
tion similar to that of the scaffold interior
during bulk degradation, when degradation is
increased. All of these factors must be taken
into account when aiming for a specifi c method
and rate of degradation.
63
].
Microparticles of PLLA and PLGA have been
shown to suppress osteoblast differentiation
early in culture [
93
]. Degradation particles
also can interact directly with osteoblasts
and affect their proliferation [
93
]. In addition,
dense fi brous capsules composed of macro-
phages and foreign-body giant cells have
formed in response to PLLA bone plates and
screws [
65
]. The properties of biomaterials
clearly affect the magnitude and duration of
the host response. Characteristics that can alter
the immune response include the size, shape,
and chemical and physical properties of the
material [
10
6.3.5 Biocompatibility
All implanted materials elicit a host reaction,
but the intensity of the response varies. Tissue
responses include infl ammation, immune reac-
tions, and variability in wound healing [
]. Therefore in designing a bio-
material, one must consider not only the
initial properties of the scaffold, but also its
degradation products and their effect on the
host.
84
]. If
a material produces minimal infl ammatory
and immune responses and functions without
84
