Biomedical Engineering Reference
In-Depth Information
absorbers” termed IVDs. The spine serves three functional roles: (1) to protect the
spinal cord, (2) to support and transmit axial loads arising from the head and torso to
the hips and lower extremities, and (3) to allow for mobility and stability such that
bending and torsional motion of the spine can occur. Without IVDs, however, the
latter two roles of the spine could not be effectively fulfilled.
The IVD is composed of three morphologically distinct regions known as the
nucleus pulposus
(NP), the
annulus fibrosus
(AF), and cartilaginous endplates
(CEP) (Fig.
1
). The NP is a hydrophilic gel-like material located within the central
region of the disc. Its material properties are largely due to its primary constituent
components: a loose network of type II collagen and the large proteoglycan
aggrecan (Fig.
1
)[
12
,
13
]. The NP is sequestered by the fibro-cartilaginous AF,
which is comprised of approximately 15-25 concentric lamellae of type I collagen
that are well adapted to resist torsional and tensile loading experienced during
bending [
13
]. The CEP is a thin layer (~0.6-1 mm) of tissue resembling articular
cartilage and lies at the interface of the IVD and vertebral bodies [
14
]. Early in
life, the CEP is thought to function as a growth plate for the vertebral bodies and
later functions to prevent the NP from extruding into the vertebral body while
potentially limiting the loss of fragmented osmotically active proteoglycan from
the IVD [
14
,
15
]. The CEP is also sufficiently permeable such that diffusion of
nutrients can occur between the vascular buds in the vertebral bodies and the largely
avascular IVD.
3
Intervertebral Disc Biochemistry and Cell Biology
The biochemical composition of the NP and AF, summarized in Table
1
, reflects the
specialized function for which each region of the IVD is adapted. The IVD is
a highly hydrated structure containing approximately 70-90% water. The major
biochemical constituents of the IVD include collagens, proteoglycans, elastin, and
non-collagenous proteins, which are differentially located throughout the IVD. The
primary biochemical component found in the NP is the proteoglycan aggrecan.
Aggrecan molecules are composed of a core protein with greater than 100 cova-
lently attached glycosaminoglycan chains (chondroitin sulfate and keratin sulfate).
These molecules complex together with hyaluronic acid via a link protein, and
together form a polyanionic bottle-brush structure. Collagen type II is the predomi-
nant form of collagen found within the NP and forms a loose network with other
minor collagens, including types IX and XI, that function as cross-bridges between
type II molecules and other extracellular matrix (ECM) components. Together, they
form an enhanced ECM network providing resistance to swelling [
16
-
19
]. Other
ECM components found within the human NP include minor collagens such as
types III and VI (found in the pericellular environment), the glycoprotein fibronec-
tin (which links matrix fibers to cell surface integrins), elastin, and the small
