Biomedical Engineering Reference
In-Depth Information
3
fibroblasts and myofibroblasts: progressive alignment, collagen production
and matrix contraction (between day 4 and day 14)
4
endothelial cells and angiogenesis (begins on day 4)
5
dermal matrix: elements of fabrication (begins on day 4, lasting 2 weeks) and
alteration (begins after week 2, lasting weeks-months).
Macrophages and related inflammatory components
After hemostasis is achieved, immune cells (in response to released chemotatic
factors) infiltrate the wound site and mount an inflammatory response. This occurs
within hours after injury, as neutrophils (in the blood) adhere to activated vascular
endothelial cells and rapidly enter the injured area. They are followed by monocytes,
which within 1-2 days, are activated to become macrophages. Together, neutrophils
and macrophages remove foreign matter, bacteria, non-functioning host cells,
damaged matrix components and other non-essential materials. Macrophages play
a critical role in the cellular phase, releasing PDGF and TGF-
to promote the
migration, proliferation and differentiation of fibroblasts and endothelial cells.
Inhibiting macrophage function may lead to a blunted inflammatory response and
a delay in wound healing.
24,25
Although lymphocytes play a major role immunosurveillance, their contribu-
tion to the early stages of wound healing is not considered to be significant.
18,20
T-cells are attracted to IL-1, but do not appear until three days after injury (when
the inflammatory response is nearing an end.) Nevertheless, lymphocytes remain
an essential part of the immune system, functioning in cell-mediated immunity (T-
cells) and humoral immunity (B-cells.)
Recently, a unique subpopulation of (mononuclear) leukocytes has been identi-
fied to be a major participant in wound healing, especially in excessive healing and
fibrosis.
26
Known as 'circulating fibrocytes,' 'peripheral blood fibrocytes' or
simply 'fibrocytes', they make up less than 1% of the circulating leukocyte
population. These cells are distinctly different from the mature resident fibroblasts
- also called fibrocytes.
27
When discovered, they were described as hematopoietic
cells with fibroblast-like (spindle-shape) morphology. Fibrocytes express a vari-
ety of surface markers, including CD34 (hematopoietic progenitor antigen) and
CD45 (common leukocytic antigen), which they maintain until later stages of
maturation.
Fibrocytes assist in the coordination of both inflammatory and reparative
responses (including wound contraction.)
27-30
Recruited to the wound site early,
they have the ability to take on an antigen-presenting role (expressing CD11b, also
expressed by monocytes/macrophages) or produce a variety of signaling mol-
ecules, including IL-1. They influence epithelial migration and proliferation (via
PDGF-
β
,
respectively), and promote fibroblast differentiation into myofibroblasts (via
TGF-
α
), recruit and activate vascular endothelial cells (via VEGF and TNF-
α
β
.) Furthermore, they have the unusual ability to secrete collagen I, as well as
