Biomedical Engineering Reference
In-Depth Information
the matrix metalloproteinase-9 (MMP-9, type IV and V collagenase.) Their
presence is thought to be in abundance in keloids and hypertrophic scars.
31
Although not yet fully elucidated, there is some evidence to suggest that fibrocytes
may be a precursor to fibroblasts and myofibroblasts (further discussion fol-
lows.)
27,28, 32,33
Epithelial-mesenchymal interaction: re-epithelialization
Within hours of skin injury, the process of re-epithelialization begins.
20,34
In the
presence of epidermal growth factor (EGF, secreted by platelets) and TGF-
β
(produced by macrophages, platelets, and keratinocytes),
14
epidermal cells un-
dergo phenotype changes that result in the abandonment of (stabilizing)
desmosome (cell-cell connection) and hemidesmosome (cell-BM connection)
expression, in favor of peripheral cytoplasmic actin filament expression, thereby
permitting cell detachment and subsequent migration (which occurs within the
first few days.)
The process of re-epithelialization requires epidermal cells (at the wound edge)
to migrate centrally, until the epidermal surface is completely restored.
20
Through
the expression of integrin (transmembrane receptor protein), epidermal cells are
able to interact with a variety of ECM ligand proteins, including fibronectin
(binding) and vitronectin (anchoring), such that desiccated eschar are undermined
and dissected out (from viable tissue) during migration. Epidermal migration is
facilitated by the production of zymogens and enzymes which assist in the removal
of fibrin clots (via plasmin) and damaged stroma (via collagenase); both plasmin
and collagenase are activated by tissue plasminogen activator (tPA), also produced
by epidermal cells.
Recent evidence indicates that re-epithelialization involves the participation of
follicular stem cells (residing in the bulge area of hair follicles) through the
Wnt
(signaling) pathway.
35
This would, therefore, explain why re-epithelialization is
impaired in deep wounds, where adnexal epithelium is partially or fully de-
stroyed.
36,37
Proliferation of keratinocytes takes place just behind the advancing front, and
continues until all layers of the epidermis are restored. In the early stages of re-
epithelialization, this process occurs mainly due to the influence of EGF and tissue
growth factor-alpha (TGF-
secreted by macrophages and epidermal cells.)
18,20
However, during the middle and later stages, the interplay between keratinocytes
and fibroblasts gradually shifts away from inflammation, in favor of granulation
tissue synthesis and basement membrane formation.
38
Such interaction relies on
the production of epithelial mitogens, mainly PDGF and keratinocyte growth
factor (KGF), by nearby fibroblasts. Although associated with platelets, PDGF is
also secreted by other mesenchymal cells (including fibroblasts), and in event of an
injury, epidermal expression of PDGF and KGF (also called fibroblast growth
factor-7, FGF-7) receptors are upregulated.
α,
