Biomedical Engineering Reference
In-Depth Information
9
Treatment of scars
Richard E. Fitzpatrick
It has been estimated that over 100 million people develop
surgical scars each year in the developed world secondary to
over 55 million elective surgeries and approximately 25 million
operations after trauma (1). There are at least an equal num-
ber of various traumatic scars including burns. Acne occurs in
approximately 50% of people and about 10% of these develop
scarring of some type, so with a population of 311 million in
the USA there will be about 15 million persons with acne scars.
There are, at least, a comparable number of scars secondary
to minor procedures, excisions, and biopsies performed in
medical offi ces.
Treatment of scars to decrease pain, pruritus, and contrac-
ture with limitations of motion or to improve their cosmetic
appearance has progressed signifi cantly over the past decade.
The visibility of a scar depends on its width, texture, color, and
fl atness. Some of these characteristics can be controlled during
the wound healing process and they can all be altered with
early intervention. Mature scars will respond to treatment as
well. As will be discussed, the orientation toward treatment of
scars has shifted to prevention of scarring preferably rather
than improvement of scars after they have healed.
As pointed out by Tsao et al. (2), there are basically three
types of scars: ( i ) atrophic (most commonly seen in acne and
chickenpox scars), ( ii ) exophytic scars (hypertrophic scars and
keloids), and ( iii ) fl at scars, which are considered normal scars
that gradually become imperceptible with time.
Abnormal wound healing results in hypertrophic scars and
keloids. These were fi rst described in the Smith Papyrus around
1700 BC (3). In 1802, Jean Louis Albert described abnormal
scarring that invaded adjacent normal tissue with extensions
similar to a crab's legs and coined the term “cheloide” to
describe this entity (4). In 1962, Mancini differentiated keloids
from hypertrophic scars by the observation that hypertrophic
scars remain confi ned to the original borders of the injury,
whereas keloids project beyond the original wound margins
(5). Distinguishing keloids from hypertrophic scars can be dif-
fi cult, particularly because the original wound margin may
remain intact but expand as more scar tissue forms, especially
with tension on the wound. This will result in a hypertrophic
scar that appears to extend beyond the borders of the original
wound, but really does not. As stated by Roseborough et al. (6),
this defi nition leads to confusion because it implies that there
is a continuum from normal scar to hypertrophic scar and
then to keloid as the scar has exceeded a vaguely defi ned wound
border. In reality, they are both unique entities.
Keloids tend to have a familial predisposition and are more
common in dark-skinned individuals, with an incidence of
6-16% in African populations (7,8). They may develop without
a known injury and do not regress spontaneously, whereas
hypertrophic scars usually occur within 8 weeks of skin trauma
and sometimes regress over a period of a few years (9).
Histologically, they both show an overabundance of collagen,
but hypertrophic scars are characterized by fi ne wavy bundles
parallel to the surface and nodules containing myofi broblasts,
whereas in keloids the collagen bundles are thicker and dis-
organized without nodules of excess myofi broblasts (10,11).
Keloid-derived fi broblasts produce increased amounts of
collagen per cell and appear to function autonomously (12).
Overall, collagen synthesis in keloids is approximately 20 times
that of normal skin (13).
A genome-wide association study (GWAS) identifi ed the
enzyme NEDD4 and its encoding gene (neural precursor cell
expressed developmentally downregulated protein 4) as one of
possible genes associated with keloid susceptibility. A possible
mechanism of NEDD4 involvement in keloid formation is
through enhancement of proliferation and invasiveness of
fi broblasts accompanied by upregulation of type I collagen
expression (14). Furthermore, NEDD4 upregulates expres-
sions of fi bronectin and also contributes to the excessive accu-
mulation of extracellular matrix (ECM) also. Fibroblasts are
considered to be the key cellular mediators of fi brogenesis in
keloid scars. Fibroblast activation protein-alfa (FAP-
) and
dipeptidyl peptidase IV (DPPIV) are proteases located at the
plasma membrane promoting cell invasiveness and tumor
growth and have been associated with keloid scars (15). A
study that associates cell invasiveness and tumor-like activity
found that FAP-
α
and DPPIV are found in increased levels in
fi broblasts taken from punch biopsies of keloid scars (15).
These proteases located at the plasma membrane promote cell
invasiveness and tumor growth. FAP-
α
and DPPIV may
increase the invasive capacity of keloid fi broblasts rather than
by modulating infl ammation or ECM production. Since FAP
expression is restricted to reactive fi broblasts in wound healing
and normal adult tissues are generally FAP-
α
α
negative, inhibit-
ing FAP-
/DPPIV activity may be a novel treatment option to
prevent keloid progression. Keloids may be best considered
almost as “tumors” of scar tissue.
Knowledge of the wound healing process is necessary to
understand when and how to intervene. There are three dis-
tinct phases: infl ammation, which occurs during the initial
48-72 hours after wounding and is characterized by recruit-
ment of various cells necessary for wound repair. The second
stage of proliferation lasts 3-6 weeks and is the time period
of deposition of the extracellular matrix as a structural
framework; myofi broblasts initiate wound contracture. The
maturation phase is the third stage that lasts as long as a year
α
192
 
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