Biomedical Engineering Reference
In-Depth Information
matrix, and the type of interactions that occur at the cell-matrix interface is required to
design biomaterials that simulate the natural environment in which these materials will
be implanted.
Cellular and Matrix Components of Bone
Osteoblasts are derived from mesencyhmal stem cells under the influence of growth fac-
tors such as bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) on
preosteoblastic cells (Baron 2003). Osteoblasts are mainly responsible for secreting the col-
lagen and ground substance matrix (osteoid), which then undergoes calcification to form
bone. Osteoblast-matrix interactions occur largely through β1 integrins, which mediate
binding to collagens and other noncollagenous proteins found in the secreted matrix and
cause activation of the mitogen-activated protein kinase (MAPK) cell signaling pathway,
resulting in osteoblastic differentiation and osteogenesis (Lian, Stein, and Aubin 2003).
After producing the osteoid matrix that calcifies, osteoblasts get trapped in the calcified
bone tissue where they then function as osteocytes. Osteocytes are found in lacunae in the
bone and interact with osteoblasts and other osteocytes, as well as the ECM via gap junc-
tions found at the end of long cytoplasmic processes. Loss of these interactions leads to
osteocyte cell death and consequent loss of bone (Baron 2003).
Osteoclasts are derived from the mononuclear/phagocytic cell lineage and are involved
in bone resorption and turnover, and indirectly in the maintenance of plasma calcium and
phosphate levels. Bone remodeling occurs during development and growth (determines
shape and size of bones) as well as in adult bones, where the bone structure is main-
tained locally by replacement of old bone by new bone (Baron 2003; Martin 1989). The main
events that occur during remodeling are (1) osteoclast activation and bone resorption,
(2) osteoclast apoptosis, (3) preosteoblast chemotaxis, proliferation, and differentiation,
and (4) formation of new bone and cessation of osteoblastic activity (Mundy, Chin, and
Oyajobi 2003). The exact mechanisms involved in the coupling of osteoclastic resorption to
osteoblastic bone formation are not completely understood, and several theories have been
suggested to explain this phenomenon. It is thought that coupling is regulated by local and
systemic chemical factors such as parathyroid hormone, 1,25-dihydroxyvitamin D, RANK
ligand and its receptors, transforming growth factor (TGFβ), BMPs, and FGFs. Another
theory is that once osteoclastic resorption is completed, osteoblasts present normally in
the bone repopulate and reline the resorbed area without the action of any humoral fac-
tors, probably by detection of the resorption site via cell surface molecules (Mundy, Chin,
and Oyajobi 2003). Imbalances in this coupling, where resorption is not followed by an
equivalent amount of formation, leads to bone loss, seen in diseases such as osteoporosis.
New bone formation can also occur in surfaces that have not been resorbed, such as in
cases of prolonged fluoride therapy and in osteoblastic metastases (Baron 2003; Lian, Stein,
and Aubin 2003; Mundy, Chin, and Oyajobi 2003; Martin 1989).
The ECM in bone is comprised of 50% to 70% inorganic mineral matrix, 20% to 40%
organic matrix, 5% to 10% water, and less than 3% lipids. The inorganic matrix is com-
posed of a hydroxyapatite mineral [Ca
10
(PO
4
)
6
(OH)
2
]. The mineral component contributes
to structural support of the skeletal system. Bone mineral is a nonstoichiometric, semicrys-
talline, calcium, and hydroxide deficient analog of hydroxyapatite. Table 1.1 shows a variety
of hydroxyapatite analogs found in bone. Most calcium phosphate precipitates containing
calcium/phosphorous ratio between 1.33 to 2.0 result in a diffraction pattern resembling
that of an apatite crystal. The apatite crystal size in bone is much smaller (~200 Å in the
smallest dimension) than its geologic analog (Robey and Boskey 2003). This size disparity
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