Biomedical Engineering Reference
In-Depth Information
myofibroblast migration from the adventitia to the neointima in arterial restenosis
after stent implantation via increased density of AT
1
and VEGFR1 receptor.
Angiotensin-2 causes ROS generation via NADPH oxidase that stimulates my-
ofibroblast migration and differentiation via AT
1
receptors and P38MAPK and
JNK kinases [
1474
]. Endothelin-1 can also trigger myofibroblast differentiation via
ET
A
receptor.
Myofibroblasts disappear at the end of tissue repair. They undergo apoptosis or
dedifferentiate in the absence of growth factors, whereas the extracellular matrix is
stabilized.
11.6.4
Healing Phases
The wound healing process has 3 distinct, overlapping phases: inflammatory
(phase
1
), proliferative (phase
2
), and maturational (phase
3
) phases.
The inflammatory phase is characterized by hemostasis and inflammation.
Blood flow is regionally regulated. Exposed collagen activates the clotting cascade
and initiates the inflammatory phase. Damaged cells release vasoconstrictors,
thromboxane-A2 and PGf2
, and wounded vessels immediately constrict to reduce
hemorrhage. Hemostatic plug that will be transformed into a stable clot occurs.
Platelets, the first responding cells, release growth factors and chemokines, such
as platelet-derived growth factor
69
and transforming growth factor,
70
which initiate
healing (Table
11.15
). Other involved growth factors include insulin-like (IGF),
epidermal (EGF),
71
and fibroblast (FGF) growth factors.
72
Fibronectin, fibrinogen,
histamine, serotonin, and von Willenbrand factor are also recruited. These mediators
control bleeding through clot formation. Platelet degranulation activates the com-
plement cascade, specifically C5a, a chemoattractant for macrophages, neutrophils,
and mastocytes, which also increases the wall permeability of nearby vessels and
stimulates LTc4 and LTd4 leukotrienes. Capillary vasodilation is later induced by
local histamine release, and inflammation cells migrate to the wound-healing locus.
The early infiltrated neutrophils are attracted by proteolytic degradation products
of fibrin, complement components C3a and C5a, CXCL4 chemokine, PDGF,
scavenger cell debris, and foreign bodies.
73
In addition, neutrophils produce elastase
α
69
Factor PDGF is chemotactic for fibroblasts, neutrophils, and macrophages. Once attracted to the
wound site, PDGF then activates macrophages and induces fibroblast proliferation.
70
Transforming growth factor is chemotactic for monocytes, lymphocytes, and fibroblasts. It
regulates matrix proteins, such as collagen, proteoglycans, fibronectin, and matrix-degrading
peptidases, and their inhibitors.
71
EGF, produced by macrophages, induces epidermal regeneration.
72
Isotypes FGF1 and FGF2 are involved in wound healing. Isoform FGF2 stimulates angiogenesis.
73
Local decontamination deals with bacterium destruction. Bacteria are phagocytosed and con-
tained within phagosomes, where they are killed by reactive oxygen species, such as superoxide,
hydroxyl free radicals, and hydrogen peroxide.
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