Biomedical Engineering Reference
In-Depth Information
In addition, blood and lymphatic vessels undergo a brief period of vasoconstriction
to minimize blood loss.
In the process of forming the fibrin clot, platelets aggregate along the injured
endothelium, where they degranulate, releasing a host of molecules that become
involved in the coagulation cascade. Consequently, fibrinogen is converted to
fibrin, which collectively assembles at the wound site, forming a fibrin clot that
provides hemostasis and early wound covering. The fibrin clot also serves as a
rudimentary matrix (or scaffold), providing support for subsequent epithelial
migration (re-epithelialization) and cellular infiltration. Aside from fibrin, the
hemostatic plug also contains important ECM ligands, including fibronectin
(collagen- and fibrin-binding protein), vitronectin (anchoring glycoprotein) and
thrombospondin (glycoprotein involved in platelet aggregation.)
Activated platelets also initiate inflammation by releasing chemotactic agents/
growth factors, including platelet-derived growth factors (PDGF) and transform-
ing growth factor-beta (TGF-
.) PDGF initiates the chemotaxis of neutrophils,
macrophages, fibroblasts and endothelial cells. TGF-
β
promotes macrophage
infiltration (into the wound site), as well as macrophage production of additional
cytokines, including fibroblast growth factor (FGF), interleukin-1 (IL-1, acute
inflammatory response) tumor necrosis factor-alpha (TNF-
β
α
, acute inflammatory
response), and even more PDGF. TGF-
β
also enhances the chemotaxis of fibroblasts
and endothelial cells.
Once hemostasis is accomplished, local endothelial cells release prostaglandins
and leukotrienes, leading to an influx of cellular elements from the systemic
circulation.
22
Prostaglandins cause vasodilatation and platelet disassembly.
Leukotrienes increase vascular permeability, chemotaxis, and leukocytic adhe-
sion.
The initiation of inflammation is also done by dermal mast cells (residing in the
perivascular region.) Mast cells also degranulate upon adequate mechanical
stimuli, liberating histamine and other vasoactive amines, causing blood vessels to
become more 'leaky' and permeable to cells. They also release inflammatory
cytokines, particularly TNF-
α
and TGF-
β
.
18,23
4.3.2
Cellular phase
As mentioned, during the cellular phase, different cell types work in unison to
mount an inflammatory response, synthesize granulation tissue, re-establish the
epithelial layer and reduce wound volume (contraction), thereby restoring a
rudimentary degree of structural integrity to the region. For simplicity, the cellular
phase may be subdivided into the following components:
1
macrophages and related inflammatory components (within 1-2 days)
2
epithelial-mesenchymal interaction: re-epithelialization (phenotype change
within hours, migration begins on day 1-2)
