Biomedical Engineering Reference
In-Depth Information
protein OB-cadherin (which is expressed by myofibroblasts, but not fibroblasts.)
40
Aside from collagen, other important ligand proteins include fibronectin and
vitronectin. Extracellular ligands fibronectin, vitronectin, and collagen, respec-
tively, which are specific to integrin receptors, are involved in myofibroblasts
adhering to, moving through, and contracting the ECM. Although distinctly
different, the myofibroblast-ECM interaction (that leads to wound contraction)
does bear some resemblance to the actin-myosin interaction (which leads to
muscle contraction, but not relaxation.)
Endothelial cells and angiogenesis
As new stroma or granulation tissue forms (around day 4), new blood vessels are
also formed to provide oxygen and nutritional support for the new tissue. Referred
to as angiogenesis, this process is stimulated by vascular endothelial growth factor
(VEGF), bFGF (basic fibroblast growth factor), and TGF-
.
14
These growth factors
are released into the wound microenvironment by macrophages, epidermal cells,
fibroblasts and endothelial cells, in response to hypoxia and high lactate levels.
The release of VEGF stimulates vascular endothelial cells to proliferate, leading
to tubular sprouting.
22
As tubules transform into capillaries, angiogenesis is further
driven by nitric oxide (NO), which is produced by local endothelial cells (via NO
synthase.) Nitric oxide is a potent vasodilator which protects tissues from hypoxia
and ischemia (although tissue hypoxia by itself also stimulates angiogenesis.)
The process of wound repair does not allow for proper reconstruction of dermal
vascular structures. Formation of new microvessels proceeds in a manner that
conforms to the overall framework of existing collagen matrix, which is dictated by
fibroblast orientation. Histologically, vascular structures found in repaired dermis
do not resemble those found in uninjured dermis.
13
In normal dermis, networks
(plexus) of microvessels are typically found to be in parallel alignments to the
epidermal surface; these microvessels have perpendicular offshoots of capillary
loops that course within the confines of the mesenchymal cones (of the papillary
dermis.) In contrast, microvessels found in repaired dermis are in perpendicular
alignment to the epidermal surface; these microvessels have ill-defined plexus and
capillary loops. As discussed above, these differences (between scar tissue and
normal skin) are due to the intrinsic nature of the reparative response favoring a
more rapid, contractile process over a slower, regenerative process.
β
Dermal matrix: elements of fabrication and alteration
In summary, the reconstruction of the acellular dermis requires fibroblast synthesis
of collagen fibers, elastic fibers and ground substance, as well as the presence of
ECM-remodeling enzymes. As alluded to earlier, under the effect of growth
factors, particularly TGF-
β
1
, fibroblasts secrete collagen into the surrounding
extracellular space (to form granulation tissue.) Intracellular assembly of collagen
