Engineering Fibrous Tissues and Their Interfaces with Bone - Structural Interfaces and Attachments in Biology - page 316

fibers and acts as a modulator of collagen fibrogenesis [ 25 ]. It is expressed in high
levels in tendons and contributes to tendon strength [ 31 ]. Biglycan is another proteo-
glycan found in tensile regions of tendons and ligaments. It can bind to collagen fibrils
as well as transforming growth factor-

) in the tissue, thus participating
in collagen fiber maturation and contributing to the regulation of cell proliferation
[ 32 , 33 ]. Aggrecan, a large aggregating proteoglycan found particularly in areas
subject to compression, possesses more than 100 chondroitin sulfate and keratin
sulfate glycosaminoglycan chains attached to the core. This negatively charged
proteoglycan increases osmotic pressure, resulting in better hydration and higher
compressive stiffness of the tissue [ 25 ].

b (TGF- b

15.2.3.4 Glycoproteins

Tendons and ligaments contain scarce amounts of several types of glycoproteins in
the ECM. Glycoproteins are made up of proteins with attached carbohydrates.
Tenascin-C and fibronectin are the main glucoproteins present in fibrous tissues.
Tenascin-C interacts with collagen fibrils to provide mechanical stability in the
ECM [ 34 ]. It is upregulated in response to mechanical loading or growth factors
like TGF- 1-integrin receptor

interactions [ 35 - 37 ]. Tenascin-C can also bind to fibronectin, which is located on
collagen surfaces and can facilitate wound healing [ 38 - 40 ]. Fibronectin may be
involved in the organization of collagen type III into bundles and has been shown to
act as a template in collagen fiber formation during remodeling [ 41 ].

and can inhibit cell adhesion by blocking

b b

15.2.4 Tendon- and Ligament-Bone Interface

The structure of the tendon-/ligament-bone interface is distinct from the structure of
the rest of the tissue. Insertion structure and composition of the fibrous tissue into the
bone varies depending on the specific attachment [ 7 ]. However, the insertion site can
be generally characterized as a fibrous enthesis (indirect) or a fibrocartilaginous
enthesis (direct) [ 42 ]. In indirect interfaces, the tendon or ligament attaches to the
bone through collagen fibers (known as Sharpy's fibers) that directly extend into
the bone at an acute angle. In direct interfaces, four transition zones of tissue exist
(Fig. 15.1 ). The first zone is characterized as fibrous connective tissue and contains a
similar structure and composition to that of normal tendon and ligament. Collagen
fibrils lay parallel to each other and fibroblasts surround the fiber matrix. The next
zone, uncalcified fibrocartilage, contains larger fibril bundles that are not aligned in a
parallel manner. Collagen type II and aggrecan are the predominant proteins found
in this region. Their presence enables resistance to compression and dissipation of
stress at the interface. This ensures that the deformation and loading of the fibrous
tissue is not concentrated at the bone surface [ 43 ]. Other collagen types, including
collagen type VI, IX, X, XI, and XII, are found in trace amounts in this area and