Biomedical Engineering Reference
In-Depth Information
Despite access to lower oxygenation, the rate of cellular proliferation is much
faster in early fetal skin (when compared to adult skin.) The mechanism behind
such efficient wound healing, in the presence of hypoxia, is not fully understood.
It appears that the lack of inflammatory cells in the fetal wound microenvironment,
the degree of fetal fibroblast differentiation, selective expression of cytokine
isoforms (primarily TGF-
β
3
), and altered proteolytic enzymes are key factors that
enable the early fetus to proceed towards a more regenerative pathway.
59,60
Fetal inflammatory response
Unlike the inflammatory response associated with post-natal wounds, the early
fetal immune system 'fails' to mount a true inflammatory response following
injury.
58-60
Fetal platelets fail to aggregate and degranulate. Likewise, the few fetal
neutrophils and fetal monocytes/macrophages present are immature, lacking
phagocytic and chemotactic potential.
Growth factors found in early fetal wounds, either have different isoforms (from
those typically seen in adult wounds), or are at a different level of concentration.
Most strikingly, early fetal wounds contain high levels of the TGF-
β
3
isoform.
TGF-
β
2
levels, thereby shifting
the healing response away from a scarring pathway and towards more regenerative
pathway.
58
Differences in levels of PDGF, FGF and VEGF are also observed
between early fetal wounds and post-natal wounds.
59,60
Although (pro-fibrotic)
PDGFs and FGFs are present in early fetal wounds, they dissipate within 24 hours
of injury. Elevated levels of VEGF in early fetal wounds are thought to promote a
more rapid angiogenic process.
β
3
downregulates (pro-fibrotic) TGF-
β
1
and TGF-
Fetal fibroblasts and fetal wound matrix
Fetal fibroblasts have innate properties (not seen in adult fibroblasts) that enable
them to repair wounds without scarring. Furthermore, the wound microenvironment,
in which they function, contains elements (such as high levels of hyaluronic acid)
that favor regeneration over repair.
Hyaluronic acid (HA), as aforementioned, is the main component of ground
substance and thus is a major component of ECM. HA is also a ligand for HA-
receptors, which are upregulated in fetal fibroblasts. HA-receptor transduction is
associated with cellular migration, adhesion and proliferation. Thus, in this
context, in which levels of HA remain elevated for three weeks in early fetal
wounds (versus low levels for less than a week in adult wounds), fetal fibroblasts
migrate, proliferate and deposit collagen faster than their adult counterparts.
59
Moreover, fetal fibroblasts have the unique ability to proliferate concurrently and
synthesize collagen (not seen in adult fibroblasts.) Owing to the inhibitory effects
of TGF-
β
3
on collagen I production, collagen deposits in early fetal wounds are
predominantly of type III.
58
