Biomedical Engineering Reference
In-Depth Information
Table 3.2.8-2 Certain applications of collagen-based biomaterials
Application
Physical state
Sutures
Extruded tape (
Schmitt, 1985
)
Hemostatic agents
Powder, sponge, fleece (
Stenzel et al. 1974; Chvapil, 1979
)
Blood vessels
Extruded collagen tube, processed human or animal blood vessel (
Nimni, 1988
)
Heart valves
Processed porcine heart valve (
Nimni, 1988
)
Tendon, ligaments
Processed tendon (
Piez, 1985
)
Burn treatment (dermal regeneration)
Porous collagen-glycosaminoglycan (GAG) copolymers (Yannas et al., 1982,
1989: Burke et al., 1981; Heimbach et al., 1988)
Peripheral nerve regeneration
Porous collagen-GAG copolymers (
Chang and Yannas, 1992
)
Meniscus regeneration
Porous collagen-GAG copolymers (Stone et al., 1997)
Skin regeneration (plastic surgery)
Porous collagen-GAG copolymers
Intradermal augmentation
Injectable suspension of collagen particles (
Piez, 1985
)
Gynecological applications
Sponges (
Chvapil, 1979
)
Drug-delivery systems
Various forms (Stenzel et al., 1974;
Chvapil, 1979
)
this region has been associated with most of the immu-
nogenicity of collagen-based implants. Several enzymatic
treatments have been devised to cleave the telopeptide
region without destroying the triple helix. Treatment of
collagen with glutaraldehyde not only reduces its degra-
dation rate by collagenase but also appears to reduce its
antigenicity. The mechanism of this effect is not well
understood.
Certain applications of collagen-based biomaterials are
shown in
Table 3.2.8-2
.
the chain. It is, nevertheless, useful for the purpose of
getting acquainted with the GAGs to show their typical
(rather, typified) repeat unit structure, as in
Fig. 3.2.8-4.
The molecular weight of many GAGs is in the range
5-60 kDa with the exception of hyaluronic acid, the
only GAG which is not sulfated; it exhibits molecular
weights in the range 50-500 kDa. Sugar units along
GAG chains are linked by a or b glycosidic bonds that are
1,3 or 1,4 (
Fig. 3.2.8-4
). There are several naturally oc-
curring enzymes which degrade specific GAGs, such as
hyaluronidase and chondroitinase. These enzymes are
primarily responsible for the physiological turnover rate
of GAGs, which is in the range 2-14 days.
The nature of the oligosaccharide linkage appears to
be identical for the GAGs, except for keratan sulfate,
and is a galactosyl-galactosyl-xylose, with the last gly-
cosidically linked to the hydroxyl group of serine in the
protein core.
The very high molecular weight of hyaluronic acid is
the basis of most uses of this GAG as a biomaterial:
Almost all make use of the exceptionally high viscosity
and the facility to form gels that characterize this poly-
saccharide. Hyaluronic acid gels have found considerable
use in ophthalmology because they facilitate cataract
surgery as well as retinal reattachment. Other reported
uses of GAGs are in the treatment of degenerative joint
dysfunction in horses and in the treatment of certain
orthopedic dysfunctions in humans. On the other hand,
sulfated GAGs are anionically charged and can induce
precipitation of collagen at acidic pH levels, a process
that yields collagen-GAG coprecipitates that can be
Proteoglycans and GAG
GAGs occur naturally as polysaccharide branches of
a protein chain, or protein core, to which they are co-
valently attached via a specific oligosaccharide linkage.
The entire branched macromolecule, which has been
described as having a ''bottle brush'' configuration, is
known as a proteoglycan and typically has a molecular
weight of about 10
3
kDa.
The structure of GAGs can be generically described as
that of an alternating copolymer, the repeat unit
consisting of a hexosamine (glucosamine or galactos-
amine) and of another sugar (galactose, glucuronic acid,
or iduronic acid). Individual GAG chains are known to
contain occasional substitutions of one uronic acid for
another; however, the nature of the hexosamine com-
ponent remains invariant along the chain. There are other
deviations from the model of a flawless alternating co-
polymer, such as variations in sulfate content along
