Biomedical Engineering Reference
In-Depth Information
of macrophages at the site increases. All tissues have resident macrophages, and their num-
ber at the injury site is enhanced by macrophages migrating from circulation. They act in
concert with the neutrophils to phagocytose cellular debris, combat any invading microor-
ganisms, and provide the source of chemoattractants and mitogens. These factors induce
the migration of endothelial cells and fibroblasts to the wound site and stimulate their
subsequent proliferation. If the infiltration of macrophages into the wound site is prevented,
the healing process is severely impaired.
The result of these initial processes is the formation of a so-called granulation tissue. It is
comprised of a dense population of fibroblasts, macrophages, and developing vasculature
that is embedded in a matrix comprised mainly of fibronectin, collagen, and hyaluronic
acid. The invading fibroblasts begin to produce collagen, mostly types I and III. The colla-
gen increases the tensile strength of the wound. Myofibroblasts actively contract at this
time, shrinking the size of the wound by pulling the wound margins together.
Over time, the matrix then undergoes remodeling, which involves the coordinated
synthesis and degradation of connective tissue proteins. Remodeling leads to a change in
the composition of the matrix as healing progresses. For instance, collagen type III is abun-
dant early on but gives way to collagen type I with time. The balance of these processes
determines the degree of scar formation. Although the wound appears healed at this time,
chemical and structural changes continue to occur within the wound site. The final step of
the wound healing process is the resolution of the scar, though in most cases this process is
incomplete and some form of scar tissue remains after healing. The formation and degrada-
tion of matrix components take place over many months. The healing process is essentially
complete when the composition of the matrix and the spatial location of the cells have
returned to close to the original state. Understanding the wound healing process is impor-
tant to the tissue engineer, since the placement of disaggregated tissues in ex vivo culture
induces responses reminiscent of the wound healing process.
6.2.7 Cell Differentiation
The coordinated activity of the cellular fate processes determines the dynamic state of
tissue function (see Figure 6.13). There is growing information available about these pro-
cesses in genetic, biochemical, and kinetic terms. The dynamics considerations that arise
from the interplay of the major cellular fate processes are introduced at the end of the chapter,
and the associated bioengineering challenges are described.
Describing Cellular Differentiation from a Biological Perspective
Differentiation is the process by which a cell undergoes phenotypic changes to become a
particular specialized cell type. This specialized cell type is characterized by its physio-
logical function and its corresponding role as part of a tissue and/or organ. This process
begins with a lineage and differentiation commitment and is followed by a coordinated
series of gene expression events.
The term
is derived from differential gene expression. Differentiation
involves a change in the set of genes that are expressed in the cell, and this change is
usually an irreversible change toward a particular functional state. This process involves
a carefully orchestrated switching off and on of gene families. The final set of genes
expressed is those that pertain to the function of the mature cell.
differentiation
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