Biomedical Engineering Reference
In-Depth Information
tightly to the surface of immune cells (lymphocytes).
The implant is eventually degraded. The reaction can
be virtually eliminated provided that the antigenic
determinants have been previously modified chemi-
cally. The immunogenicity of polysaccharides is typically
far lower than that of proteins. The collagens are gener-
ally
naturally occurring, or native, macromolecular struc-
tures. Certain modified forms of these polymers are also
described.
Structure of native collagen
weak
immunogens
relative
to
the
majority
of
proteins.
Another potential problem in the use of natural
polymers as biomaterials derives from the fact that these
polymers typically decompose or undergo pyrolytic
modification at temperatures below the melting point,
thereby precluding the convenience of high-temperature
thermoplastics processing methods, such as melt extru-
sion, during the manufacturing of the implant. However,
processes for extruding these temperature-sensitive
polymers at room temperature have been developed.
Another serious disadvantage is the natural variability in
structure of macromolecular substances which are de-
rived from animal sources. Each of these polymers ap-
pears as a chemically distinct entity not only from one
species to another (species specificity) but also from one
tissue to the next (tissue specificity). This testimonial to
the elegance of the naturally evolved design of the
mammalian body becomes a problem for the manufac-
turer of implants, which are typically required to adhere
to rigid specifications from one batch to the next. Con-
sequently, relatively stringent methods of control of the
raw material must be used.
Most of the natural polymers in use as biomaterials
today are constituents of the ECM of connective tissues
such as tendons, ligaments, skin, blood vessels, and bone.
These tissues are deformable, fiber-reinforced compos-
ite materials of organ shape as well as of the organism
itself. In the relatively crude description of these tissues
as if they were manmade composites, collagen and
elastin fibers mechanically reinforce a ''matrix'' that
primarily consists of protein polysaccharides (pro-
teoglycans) highly swollen in water. Extensive chemical
bonding connects these macromolecules to each other,
rendering these tissues insoluble and, therefore, impos-
sible to characterize with dilute solution methods unless
the tissue is chemically and physically degraded. In the
latter case, the solubilized components are subsequently
extracted and characterized by biochemical and physi-
cochemical methods. Of the various components of
extracellular materials that have been used to fashion
biomaterials, collagen is the one most frequently used.
Other important components, to be discussed later,
include the proteoglycans and elastin.
Almost inevitably, the physicochemical processes
used to extract the individual polymer from tissues,
as well as subsequent deliberate modifications, alter
the native structure, sometimes significantly. The de-
scription in this section emphasizes the features of the
Structural order in collagen, as in other proteins, occurs
at several discrete levels of the structural hierarchy. The
collagen in the tissues of a vertebrate occurs in at least
10 different forms, each of these being predominant in
a specific tissue. Structurally, these collagens share the
characteristic triple helix, and variations among them are
restricted to the length of the nonhelical fraction, as well
as the length of the helix itself and the number and
nature of carbohydrates attached on the triple helix. The
collagen in skin, tendon, and bone is mostly type I col-
lagen. Type II collagen is predominant in cartilage, while
type III collagen is a major constituent of the blood
vessel wall as well as being a minor contaminant of type I
collagen in skin. In contrast to these collagens, all of
which form fibrils with the distinct collagen periodicity,
type IV collagen, a constituent of the basement mem-
brane that separates epithelial tissues from mesodermal
tissues, is largely nonhelical and does not form fibrils. We
follow here the nomenclature that was proposed by
W. Kauzmann (1959) to describe in a general way the
structural order in proteins, and we specialize it to the
case of type I collagen ( Fig. 3.2.8-1 ).
The primary structure denotes the complete sequence
of amino acids along each of three polypeptide chains as
well as the location of interchain cross-links in relation to
this sequence. Approximately one-third of the residues
are glycine and another quarter or so are proline or
hydroxyproline. The structure of the bifunctional in-
terchain cross-link is the relatively complex condensation
product of a reaction involving lysine and hydroxylysine
residues; this reaction continues as the organism ma-
tures, thereby rendering the collagens of older animals
more difficult to extract from tissues.
The secondary structure is the local configuration
of a polypeptide chain that results from satisfaction of
stereochemical angles and hydrogen-bonding potential of
peptide residues. In collagen, the abundance of glycine
residues (Gly) plays a key configurational role in the
triplet Gly-X-Y, where X and Y are frequently proline or
hydroxyproline, respectively, the two amino acids that
control the chain configuration locally by the very rigidity
of their ring structures. On the other hand, the absence
of a side chain in glycine permits close approach of
polypeptide chains in the collagen triple helix.
Tertiary structure refers to the global configuration
of the polypeptide chains; it represents the pattern
according to which the secondary structure is packed
within the complete macromolecule and it constitutes
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