Biomedical Engineering Reference
In-Depth Information
polymer may need to function on the order of days to
months. Scaffolds intended for the reconstruction of
bone illustrate this point: In most applications, the
scaffold must maintain some mechanical strength to
support the bone structure while new bone is formed.
Premature degradation of the scaffold material can be as
detrimental to the healing process as a scaffold that re-
mains intact for excessive periods of time. The future use
of tissue engineering scaffolds has the potential to revo-
lutionize the way aging-, trauma-, and disease-related loss
of tissue function can be treated.
Multifunctional devices
,
as the name implies,
combine several of the functions just mentioned within
one single device. Over the past few years, there has
been a trend toward increasingly sophisticated applica-
tions for degradable biomaterials. Usually, these appli-
cations envision the combination of several functions
within the same device and require the design of
custom-made materials with a narrow range of prede-
termined materials properties. For example, the avail-
ability of biodegradable bone nails and bone screws
made of ultrahigh-strength poly (lactic acid) opens the
possibility of combining the ''mechanical support''
function of the device with a ''site-specific drug de-
livery'' function: a biodegradable bone nail that holds
the fractured bone in place can simultaneously stimu-
late the growth of new bone tissue at the fracture site by
slowly releasing bone growth factors (e.g., bone mor-
phogenic protein (BMP) or transforming growth factor
b) throughout its degradation process.
Likewise, biodegradable stents for implantation into
coronary arteries are currently being investigated (
Agrawal
et al.
, 1992
). The stents are designed to mechani-
cally prevent the collapse and restenosis (reblocking) of
arteries that have been opened by balloon angioplasty.
Ultimately, the stents could deliver an antiinflammatory
or antithrombogenic agent directly to the site of vascular
injury. Again, it would potentially be possible to combine
a mechanical support function with site specific drug
delivery.
Various functional combinations involve the tissue
engineering scaffold. Perhaps the most important mul-
tifunctional device for future applications is a tissue en-
gineering scaffold that also serves as a drug delivery
system for cytokines, growth hormones, or other agents
that directly affect cells and tissue within the vicinity of
the implanted scaffold. An excellent example for this
concept is a bone regeneration scaffold that is placed
within a bone defect to allow the regeneration of bone
while releasing BMP at the implant site. The release of
BMP has been reported to stimulate bone growth and
therefore has the potential to accelerate the healing rate.
This is particularly important in older patients whose
natural ability to regenerate tissues may have declined.
The process of bioerosion
One of the most important prerequisites for the suc-
cessful use of a degradable polymer for any medical ap-
plication is a thorough understanding of the way the
device will degrade/erode and ultimately resorb from the
implant site. Within the context of this section, we are
limiting our discussion to the case of a solid, polymeric
implant. The transformation of such an implant into
water-soluble material(s) is best described by the term
''bioerosion.'' The bioerosion process of a solid, polymeric
implant is associated with macroscopic changes in the
appearance of the device, changes in its physico-
mechanical properties and in physical processes such as
swelling, deformation, or structural disintegration, weight
loss, and the eventual depletion of drug or loss of function.
All of these phenomena represent distinct and often
independent aspects of the complex bioerosion behavior
of a specific polymeric device. It is important to note that
the bioerosion of a solid device is not necessarily due to
the chemical cleavage of the polymer backbone or the
chemical cleavage of cross-links or side chains. Rather,
simple solubilization of the intact polymer, for instance,
due to changes in pH, may also lead to the erosion of
a solid device.
Two distinct modes of bioerosion have been described
in the literature. In ''bulk erosion,'' the rate of water
penetration into the solid device exceeds the rate at
which the polymer is transformed into water-soluble
material(s). Consequently, the uptake of water is
followed by an erosion process that occurs throughout
the entire volume of the solid device. Because of the
rapid penetration of water into the matrix of hydrophilic
polymers, most of the currently available polymers will
give rise to bulk eroding devices. In a typical ''bulk ero-
sion'' process, cracks and crevices will form throughout
the device that may rapidly crumble into pieces. A good
illustration for a typical bulk erosion process is the dis-
integration of an aspirin tablet that has been placed into
water. Depending on the specific application, the often
uncontrollable
tendency
of
bulk
eroding
devices
to
crumble into little pieces can be a disadvantage.
Alternatively, in ''surface erosion,'' the bioerosion
process is limited to the surface of the device. Therefore,
the device will become thinner with time, while main-
taining its structural integrity throughout much of the
erosion process. In order to observe surface erosion, the
polymer must be hydrophobic to impede the rapid im-
bibition of water into the interior of the device. In addi-
tion, the rate at which the polymer is transformed into
water-soluble material(s) has to be fast relative to the rate
of water penetration into the device. Under these condi-
tions, scanning electron microscopic evaluation of surface
eroding devices has sometimes shown a sharp border
