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Minimally Invasive Percutaneous Collagen Induction

  • Groote Schuur Hospital and private practice

Abstract and Figures

PCI is a simple technique and, with the right tool, can thoroughly puncture any skin easily and quickly. Although a single treatment may not give the smoothing that is seen with laser resurfacing, the epidermis remains virtually normal. When the result is not sufficient, treatment can be repeated. The technique can be used on areas that are not suitable for peeling or laser resurfacing.
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Minimally Invasive Percutaneous Collagen Induction
Desmond Fernandes, MB, BCh, FRCS(Edin)
The Shirnel Clinic and Department of Plastic Reconstructive Surgery, University of Cape Town, 822 Fountain Medical Centre,
Heerengracht, Cape Town 8001, South Africa
We live in a time when more people are living to a
greater age than ever before. At the same time, there
is an accent on youth such that our patients are ask-
ing us to make them look as young as possible.
Obviously, surgery helps restructure the face into a
more youthful shape, but the old skin remains. Today,
many patients come before they need surgery,
searching for a rapid solution that will make them
look 10 years younger. How do we help our older
cosmetic patients or the much younger men and
women who want to prolong their tenure in a
youthful bracket?
This quest for younger-looking skin has spawned
many different topical techniques that share the same
principle of damaging the skin to cause fibrosis. The
fibrosis then causes tightening of the skin. Histori-
cally, skin peels were the first method of skin
rejuvenation. The principle of peeling is to destroy
the epidermis partially or almost completely to
damage the fibroblasts and dermal structures. This
damage then sets up an inflammatory response
proportional to the damage, which results in the
deposition of collagen. Peeling sacrifices the epider-
mis to achieve the desired result. The experience with
partial-depth burns misled many into believing that
the epidermis is a self-renewing organ that rapidly
grows over the damaged area, which is why peels
became progressively more destructive for the epi-
dermis (eg, the deep phenol peel) until the accumu-
lated problems forced clinicians to recognize that
smoother skin comes at a very heavy price for many
patients and also leads to a significant thinning of
the skin many years later. The proponents of peeling
looked only at the increase of collagen in the
papillary and reticular dermis but did not pay any
attention to the epidermis. The epidermis suffered by
becoming less undulating due to the destruction of
the dermal papillae and subsequent impaired nourish-
ment and, in turn resulted in a thinner epidermis with
fewer cells in the stratum spinosum than before
treatment. The stratum corneum is then less likely to
act as an efficient barrier, so it is not surprising that
many patients feel that their skin is too dry for years
after the treatment. Consequently, hydration of the
dermis also is affected.
Lighter peels (eg, Jessner’s and trichloracetic acid
(TCA)) were introduced, but the tightening of skin
was less effective. For some reason, which is difficult
to understand, clinicians in the late 1980s turned to
laser to destroy the epidermis even more thoroughly
to tighten the skin. We were told that laser would not
present the same problems as the heavy phenol peels
and that skin color and texture would be superior.
Smoothing skin is still most effectively done by CO
laser through the aggressive heat damage that is
caused. No other technique can match it, but at the
same time, CO
laser causes the most complications.
A significant problem is that deep treatments like this
stimulate fibrosis rather than new, naturally oriented
collagen formation. This fibrosis may result in a
much whiter reflectance from the dermis, giving the
skin an unnatural pallor. The sad fact is that several
years after the treatment, the collagen will be
1042-3699/05/$ – see front matter D2005 Elsevier Inc. All rights reserved.
The author, a plastic and reconstructive surgeon practic-
ing in Cape Town, is the medical consultant for Environ
Cosmeceutics International and Vivida Closed Corporation
(c.c.), Cape Town, South Africa. Vivida c.c. is the
manufacturer of the Environ Roll-Cit. Dr. Fernandes has a
financial interest in both of these companies.
E-mail address:
Oral Maxillofacial Surg Clin N Am 17 (2005) 51 – 63
resorbed—as all scar collagen is—and fine wrinkles
will start to show as a result of the thin epidermis with
no dermal papillae. The impaired hydration of the
skin means that it is not as plump as it could be and
can look atrophic due to this excessive destruction.
Why destroy the epidermis to make the skin
smoother? The epidermis is an extremely complex,
highly specialized organ. It may be only 0.2 mm thick
but it is our sole protection from the environment.
We should never damage the epidermis unless the
risk of leaving the epidermis intact is greater than the
risk of removing it. Wrinkles are hardly a good ex-
cuse to destroy this wonderfully complex interface
that we have with the world. Whatever we do, we
should try to ensure that the basic normal architecture
of the skin is never altered. To rejuvenate facial skin
and really look young, we need a perfect epidermis
with natural dermal papillae, good hydration, normal
color, and normal resilience.
The problem with most treatments that are used is
that only the face can successfully be treated. In
addition, if the result after one treatment is inade-
quate, then a repeated treatment cannot easily be
done. Clinicians have concentrated on rejuvenating
the face, with the result that we get patients with a
younger-looking face but with older hands, arms,
and trunk. We need to treat not only the face but the
hands, arms, trunk, and legs. Laser, however, has
extremely limited indications for areas other than the
face. Laser treatment is not real rejuvenation and will
not satisfy patients who are looking for a more
complete rejuvenation.
This article is devoted to a technique that lends
itself to treatment of the face and the body to achieve
collagen induction. Although this technique may
seem new, we have had centuries of experience with
the technique of tattooing, but in this case, there is no
pigment used. There are now a growing number of
clinicians who believe that we can get closer to our
patients’ dreams of rejuvenation by pricking skin with
needles to get percutaneous collagen induction (PCI).
Principles of the needling technique
Orentreich and Orentreich [1] described ‘‘subci-
sion’’ as a way of building up connective tissue be-
neath retracted scars and wrinkles. The author [2],
simultaneously and independently, used a similar
technique to treat the upper lip by sticking a 15-gauge
needle into the skin and then tunneling under the
wrinkles in various directions, parallel to the skin
surface. The lip wrinkles were improved in many
cases, but the problem was that bleeding caused
severe and unacceptable bruising, which sometimes
resulted in hard nodules. Camirand and Doucet [3]
treated scars with a tattoo gun to ‘‘needle abrade’
them. Although this technique can be used on ex-
tensive areas, it is laboriously slow and the holes in
the epidermis are too close and too shallow. These
techniques work because the needles break old col-
lagen strands in the most superficial layer of the
dermis that tether scars or wrinkles. It is presumed
that this process promotes removal of damaged col-
lagen and induces more collagen immediately under
the epidermis. The author believes that the standard
technique of tattooing is too superficial to give good
effects for thicker scars or for stimulating collage-
Fig. 1. Needling the face for refining wrinkles using the
special tool designed for PCI.
Fig. 2. Histologic section of skin showing puncture sites
where the needle has penetrated (arrows) and generally
divided cells from each other rather than cutting through the
cells. The tracts are curved, reflecting the path of the needle
as it rolls into and then out of the skin. The holes are about
four cells wide and will heal rapidly. Note that the epidermis
and particularly the stratum corneum is intact except for
these tiny holes (hematoxylin-eosin, original magnification
nosis in the reticular dermis. Needles need to pene-
trate relatively deeply to stimulate the production of
elastin fibers oriented from the deep layers of the
dermis to the surface. Based on these principles, the
author designed a special tool for PCI [4] (Fig. 1).
Indications for needling
Indications for percutaneous collagen induction
1. To restore skin tightness in the early stages of
facial aging. This procedure is relatively minor
and can safely be recommended. Some patients
who are worried about cosmetic surgery may
be satisfied with simple PCI. The neck, arms,
abdomen, thighs, and areas between the breasts
and buttocks also can be treated. Upper-lip
creases can respond very well to needling
(Figs. 2 4) but may give an even better result
when combined with fat grafts.
2. Fine wrinkles are an excellent indication for
needling of the skin.
3. Acne scarring—the skin becomes thicker and
the results are superior to dermabrasion.
4. To tighten skin after liposuction.
5. Stretch marks (Fig. 5).
6. Lax skin on the arms (Fig. 6) and abdomen
(Fig. 7).
7. Scars—if they are white, then they can become
more skin colored.
8. Hypertrophic burn scars—PCI can safely be
used in children and may avoid procedures to
release contractures.
Contraindications for percutaneous collagen
1. Patients who have not pretreated their skin with
vitamin A.
2. Presence of skin cancers, warts, solar keratoses,
or any skin infection. The needles may
disseminate abnormal cells by implantation.
3. Active acne or herpes labialis infections in the
face or impetigo lesions anywhere on the body.
4. Patients on any anticoagulant therapy like
warfarin, heparin, and other oral anticoagu-
lants. The presence of these drugs may cause
excessive, uncontrolled bleeding. Patients pre-
viously on such treatment should have their
coagulation status checked before the treatment
to confirm that they have a normal clotting/
bleeding profile.
5. Many patients take aspirin daily for medical or
health reasons. The aspirin should be stopped at
least 3 days before the procedure.
6. Allergy to local anesthetic agents or general
anesthesia. These patients should be assessed
by a specialist anesthetist before treatment.
7. Patients on chemotherapy, high doses of
corticosteroids, or radiotherapy.
8. Patients with uncontrolled diabetes mellitus.
9. Patients with an extremely rare but severe form
of keloid scarring in which virtually every pin-
prick becomes a keloid. Patients often have
keloids on the palms of the hands or soles of
the feet.
Fig. 3. Histologic section shows that the needle tract
penetrates to a depth of about 1.5 to 2 mm through the
papillary dermis into the reticular dermis (hematoxylin-
eosin, original magnification 40).
Fig. 4. Appearance of the skin immediately after PCI. The
skin has been cleaned thoroughly and areas of cyanosis can
be seen.
minimally invasive percutaneous collagen induction 53
Preparing the skin
To achieve youthful skin, one needs the skin to be
functionally as young as possible. Most patients
coming for rejuvenation have photoaging and this
needs to be addressed before attempting any PCI.
Photoaging not only is due to the actual ultraviolet
damage of dermal tissues but also is the result of a
chronic deficiency of vitamin A. [5] The first step
toward skin health is to topically replace photo-
sensitive vitamin A [6] and the other antioxidants
vitamins C and E and carotenoids, which are nor-
mally lost on exposure to light. Vitamin A is utterly
essential for the normal physiology of skin and yet
it is destroyed by exposure to light so that it is
prevented from exerting its important influence on
skin and preserving collagen. Vitamin A is believed
to control between 350 to 1000 genes that control
normal function, proliferation, and differentiation of
cells. One cannot exaggerate the value of vitamin A
in a rejuvenation program for skin, especially with
PCI, because in this case, we are specifically trying to
stimulate cells to induce collagen to their maximum.
Vitamin A in physiologic doses will stimulate cell
growth, the release of growth factors, angiogenesis
[7], and the production of healthy new collagen. The
DNA effects of vitamin A interact in parallel with the
growth factors released by PCI. Adequate nourish-
ment of the skin with vitamin A (not necessarily as
Fig. 6. (Left image) Histology shows thigh skin before PCI. (Right image ) Six months after PCI, more collagen (pink ) and elastin
(brown) can be detected. Although difficult to estimate, there is at least 400% more collagen and elastin in the postprocedure
histology section (Giemsa, original magnification 40).
Fig. 5. This slide illustrates the ease with which Indian ink
passively penetrates the skin after needling. Skin was
removed from the upper eyelid and then later needled.
Following needling, Indian ink was applied to the surface
and allowed to dry before the specimen was placed in
formalin for histologic examination. Notice that the ink has
penetrated the papillary dermis. The lesson from this
procedure is that clinicians and patients must be cautious
about what is applied to the surface of the skin after needling.
retinoic acid but also as retinyl esters, retinal, or
retinaldehyde) will ensure that the metabolic pro-
cesses for collagen production will be maximized and
the skin will heal as rapidly as possible [8].
Vitamin C is similarly important for collagen
formation but is destroyed by exposure to blue light.
Both of these vitamins need to be replaced every day
so that the natural protection and repair of DNA can
be maintained. As a result, the skin will take on a
more youthful appearance. The addition of palmitoyl
pentapeptide or other similar peptides also will ensure
that better collagen will be formed. The use of a
special device for microneedling of the skin (Environ
Cosmetic Roll-Cit, Vivida c.c., Cape Town, South
Africa) will ensure that higher doses of the active
ingredients get into the skin. These chemicals,
however, cannot achieve really youthful skin because
the collagen immediately below the epidermis has
been destroyed by years of sun exposure and the
production of collagen in this area needs to be
stimulated by a more targeted technique.
Technique of percutaneous collagen induction
The skin is routinely prepared by using topical
vitamin A and C and antioxidants for at least 3 weeks,
but preferably for 3 months if the skin is very sun
damaged. If the stratum corneum is thickened and
rough, a series of mild TCA peels (2.5% – 5% TCA in
a special gel formulation) will get the surface of the
skin prepared for needling and maximize the result.
Under topical, local, or general anesthesia, the
skin is closely punctured with the special tool that
consists of a rolling barrel with needles at regular
intervals. By rolling backward and forward with
Fig. 8. Phase II of the inflammatory response, which is predominantly the stage of tissue proliferation. Monocytes, keratinocytes,
and fibroblasts continue to influence and be influenced by the release of growth factors. Keratinocytes stimulate growth of the
epidermis and release growth factors to promote collagen deposition by the fibroblasts. New blood vessels are created, and there
is a surge of matrix deposition. GAGs, glycosaminoglycans.
Fig. 7. Phase I of the inflammatory response showing the cascade of cytokines and growth factors following the initial injury of
needling. At this stage, neutrophils are the dominant leucocytes but are gradually replaced by monocytes, the dominant
leucocytes in phase II.
minimally invasive percutaneous collagen induction 55
some pressure in various directions one can achieve
an even distribution of the holes. The skin should be
needled as densely as possible. Usually, as the needle
holes get too close to each other, the needle ‘‘slips’’
into an established hole and so it seems impossible to
over treat the skin. For very superficial small scars, I
use a simple tattoo-artist’s gun as described by
Camirand and Doucet [3]. When using the tattoo-
artist’s machine, one has to be very careful not to
overtreat an area because the skin can then be
damaged because the needles plough their way
through the skin and may remove the epidermis.
The needles penetrate through the epidermis (Fig. 8)
but do not remove it, so the epidermis is only
punctured and will rapidly heal. The needle seems to
divide cells from each other rather than cutting
through the cells so that many cells are spared.
Because the needles are set in a roller, the needle
initially penetrates at an angle and then goes deeper
as the roller turns. Finally the needle is extracted at
the converse angle and therefore the tracts are curved,
reflecting the path of the needle as it rolls into and
then out of the skin. The epidermis and particularly
the stratum corneum remain intact, except for these
tiny holes, which are about four cells in diameter. The
needles penetrate about 1.5 to 2 mm into the dermis
(Fig. 9). Naturally, the skin bleeds for a short time,
but that soon stops. The skin develops multiple
microbruises in the dermis that initiate the complex
cascade of growth factors that eventually results in
collagen production (Fig. 10). After the bleeding
stops, there is a serous ooze that has to be removed
from the surface of the skin. Wet gauze swabs soak
up most of the serous ooze. As the skin swells, the
holes are closed, the edges of the epidermis are
approximated, and the ooze stops. Noxious chemi-
cals, however, may still penetrate the skin, so only
safe molecules should be used topically (Fig. 11).
After this serous leak has stopped, the skin is washed
thoroughly and then covered with vitamin A, C, and
Fig. 9. The final remodeling phase of healing after PCI, which takes many months. Collagen type III is converted into collagen
type I, and the skin becomes tighter. Blood supply is normalized, so the skin becomes smoother and has a natural color.
Fig. 10. Appearance of the skin 2 days after PCI.
Fig. 11. Appearance of the skin 5 days after PCI. Makeup
can be used from about the fourth to the fifth day with-
out problems.
E oil or cream (do not use ascorbic acid). The patient
is warned that they will look terribly red and bruised,
and they are encouraged to shower within a few hours
of the procedure, when they return home.
Why percutaneous collagen induction works
PCI results from the natural response to wounding
of the skin, even though the wound is minute and
mainly subcutaneous. A single needle prick through
the skin would cause an invisible response. It is
necessary to understand that when the needle pene-
trates into the skin, this injury, minute as it might
seem, causes some localized damage and bleeding
by rupturing fine blood vessels. Platelets are auto-
matically released and the normal process of inflam-
mation commences, even though the wound is
miniscule. A completely different picture emerges
when thousands or tens of thousands of fine pricks
are placed close to each other and one gets a field
effect, because the bleeding is virtually confluent.
This promotes the normal post-traumatic release of
growth factors and infiltration of fibroblasts. This
reaction is automatic and produces a surge of activity
that inevitably leads to the fibroblasts being
‘‘instructed’’ to produce more collagen and elastin.
The collagen is laid down in the upper dermis just
below the basal layer of the epidermis (Fig. 12).
It now becomes important to understand the
process of inflammation in detail. An excellent ref-
erence on this topic is the chapter ‘‘Wound Healing’
by Falabela and Falanga in The Biology of the Skin
[9]. There are three phases in wound healing:
Phase I: inflammation, which starts immediately
after the injury
Phase II: proliferation (tissue formation), which
starts after about 5 days and lasts about 8 weeks
Phase III: tissue remodeling, from 8 weeks to
about 1 year
Phase I: initial injury
The inflammation phase starts when the needles
prick the skin and rupture blood vessels and blood
cells and serum gets into the surrounding tissue
(Fig. 13). Platelets are important in causing clotting
and releasing chemotactic factors, which cause an
invasion of other platelets, leucocytes, and fibro-
blasts. The leucocytes, particularly neutrophils, then
act on the damaged tissue to remove debris and kill
bacteria. After the platelets have been activated by
exposure to thrombin and collagen, they release
numerous cytokines. This process involves a complex
Fig. 12. Mirror image of the right eye of a patient who had
PCI of the lower-eyelid skin done in conjunction with an
upper blepharoplasty and lateral elevation of the eyebrow in
a scarless technique devised by the author. The left image
shows the right eyelid preoperatively and the right image
shows the eyelid 6 months postoperatively.
Fig. 13. (A) Upper lip before PCI showing lipstick tracking up the creases. (B) Fourteen months after one PCI treatment. No
fillers have been used.
minimally invasive percutaneous collagen induction 57
concatenation of numerous factors that are impor-
tant in (1) controlling the formation of a clot
(eg, fibrinogen, fibronectin, von Willebrand factor,
thrombospondin, ADP, and thromboxane); (2) in-
creasing vascular permeability, which then allows
the neutrophils to pass through the vessel walls and
enter the damaged area; (3) attracting neutrophils
and monocytes; and (4) recruiting fibroblasts into the
wounded area.
Of special interest in understanding the action of
PCI are the following:
1. Fibroblast growth factor: promotes not only
fibroblast proliferation but also epidermal pro-
liferation and stimulates the production of new
blood vessels. Vitamin A is an essential
regulator of differentiation of fibroblasts and
keratinocytes so adequate doses in the tissues
are required at this stage. In anticipation of the
interrupted blood supply, it should be ensured
that the highest-possible normal levels of
vitamin A are stored in the skin before PCI.
2. Platelet-derived growth factor: chemotactic for
fibroblasts and promotes their proliferation,
meaning that more collagen and elastin will
be made. The need for vitamin C at this stage
becomes crucial because without adequate
levels of this vitamin, proline and lysine cannot
be incorporated into collagen and the strands
will then be defective.
3. Transforming growth factor a(TGF-a): facili-
tates re-epithelialization. In the case of PCI,
re-epithelialization is not an important action.
4. Transforming growth factor b(TGF-b): a
powerful chemotactic agent for fibroblasts that
migrate into the wound about 48 hours after
injury and start producing collagen types I and
III, elastin, glycoseaminoglycans, and proteo-
glycans. Collagen type III is the dominant form
of collagen in the early wound-healing phase.
Again, this action is heavily dependent on
adequate doses of vitamin C. At the same time,
TGF-binhibits proteases that break down the
intercellular matrix.
5. Connective tissue activating peptide III: also
promotes the production of intercellular matrix.
Fibroblasts migrate into the area, and this surge
of activity inevitably leads to the production of
more collagen and more elastin. Vitamin A and
C again are important mediators of this action.
6. Neutrophil activating peptide-2: has a chemo-
tactic effect for neutrophils that then migrate
into the wounded area. Neutrophils are impor-
tant for killing bacteria and helping to debride
tissue but, in the case of PCI, their main action
is the release of cytokines that enhance the
effects of the platelet cytokines (eg, platelet-
derived growth factor and connective tissue
growth factor).
Phase II: the period for tissue proliferation
As time passes, probably about 5 days in the case
of PCI, neutrophils are replaced by monocytes
(Fig. 14). The monocytes differentiate into macro-
phages and phagocytose the decaying neutrophils.
They are very important for the later healing phases
because they remove cellular debris and release
several growth factors including platelet-derived
growth factor, fibroblast growth factor, TGF-b, and
TGF-a, which stimulate the migration and prolifera-
tion of fibroblasts and the production and modula-
tion of extracellular matrix. With PCI, there is only
extravasated blood and very little connective tissue
damage to be dealt with. Bacterial infection is rare,
but it has been noticed that when the needled area
gets infected, greater smoothing of skin may occur,
probably due to a heightened growth factor response.
In standard wounds, the inflammatory phase ends
after about 5 to 6 days, as proliferation and tissue
formation ensue. In these cases, the main cell is the
keratinocyte. Keratinocytes change in morphology
and become mobile to cover the gap in the basement
membrane. The changes include retraction of tono-
filaments and the dissolution of desmosomes and
hemidesmosomes so that the cells can migrate. Pe-
ripheral cytoplasmic actin filaments also are devel-
oped that ‘‘pull’’ keratinocytes together to close the
wound. These actin filaments, however, are not an
important factor in PCI because re-epithelialization,
or the closure of the needle holes, occurs within a
few hours after needling because the gap is so small.
Disruption of the basement membrane by PCI de-
stroys the lamina lucida and brings basal keratino-
cytes into direct contact with the underlying collagen,
which inactivates laminin and stimulates keratinocyte
migration. When the keratinocytes have joined
together, they start producing all the components to
re-establish the basement membrane with laminin
and collagen types IV and VII. A day or two after PCI,
the keratinocytes start proliferating and act more in
thickening the epidermis than in closing the defect.
Initially after PCI, the disruption of the blood
vessels causes a moderate amount of hypoxia. The
low oxygen tension stimulates the fibroblast to
produce more TGF-b, platelet-derived growth factor,
and endothelial growth factor. Procollagen mRNA
also is upregulated, but this cannot cause collagen
formation because oxygen is required (which only
occurs when re-vascularization occurs). Collagen
type III is the dominant form of collagen in the early
wound-healing phase and becomes maximal 5 to
7 days after injury. The longer the initial phase, the
greater the production of collagen type III.
If the injury extends deeper than the adnexal
structures, then myofibroblasts may contract the
wound considerably. Although the injury in skin
needling extends deeper than the adnexal structures,
because the epithelial wounds are simply cleft,
myofibroblast wound contraction may not play a part
in the healing.
A number of proteins and enzymes are important
for fibroplasia and angiogenesis that develop at the
same time. Anoxia, TGF-b, and fibroblast growth
factor and other growth factors play an important
part in angiogenesis. Fibroblasts release insulinlike
growth factor that is an important stimulant for
proliferation of fibroblasts themselves and endothelial
cells. Insulinlike growth factor is essential in neo-
vascularisation. Insulinlike growth factor or somato-
medin-C also is one of the main active agents for
growth hormone.
Integrins facilitate the interaction of the fibro-
blasts, endothelial cells, and keratinocytes.
Phase III the process of tissue remodeling
Tissue remodeling continues for months after the
injury and is mainly done by the fibroblasts (Fig. 15).
By the fifth day after injury, the fibronectin matrix is
laid down along the axis in which fibroblasts are
aligned and in which collagen will be laid down.
TGF-band other growth factors play an important
part in the formation of this matrix. Collagen type III
is laid down in the upper dermis just below the basal
layer of the epidermis.
Collagen type III is gradually replaced by
collagen type I over a period of a year or more,
which gives increased tensile strength. The matrix
metalloproteinases (MMPs) are essential for the con-
version process. The various MMPs are generally
Fig. 15. Mirror image of the right side of the face
preoperatively (left image) and 4 months after whole face
needling (right image). The upper lip was initially needled
three times 2 years before, at monthly intervals. The lower
eyelid has been needled only once.
Fig. 14. (A) Before PCI. (B) One year after treatment of PCI.
minimally invasive percutaneous collagen induction 59
classed as MMP-1 (collagenases), MMP-2 (gelatin-
ases), and MMP-3 (stromelysins).
Care of the skin after percutaneous collagen
Immediately after the treatment, the skin looks
bruised, but bleeding is minimal and there is only a
small ooze of serum that soon stops. The author
recommends soaking the skin with saline swabs for
an hour or two and then cleaning the skin thoroughly
with a Tea Tree Oil based cleanser. The patient is
encouraged to use topical vitamin A and vitamin C as
a cream or an oil to promote better healing and
greater production of collagen. The addition of
peptides like palmitoyl pentapeptide could possibly
ensure even better results.
At home, the patient should stand under a shower
for a long time, allowing the water to soak into the
surface of the skin. Bathing is discouraged because of
potential contamination from drains and plugs.
Patients should be reminded to use only tepid water
because the skin will be more sensitive to heat. While
the water is running over the face or body, the pa-
tient should gently massage the treated skin until all
serum, blood, or oil is removed. The importance of
a thorough but gentle washing of the skin, a few
hours after the procedure, cannot be stressed enough.
The skin will feel tight and may look uncomfort-
able in a few cases. Most patients say that the skin is
a little sensitive but the major complaint is about the
bruising and swelling. The following day, the skin
looks less dramatic (Fig. 16) and by day 4 or 5, the
skin has returned to a moderate pink flush, which can
easily be concealed with makeup (Fig. 17). Men
usually seem to heal faster and are less bruised than
women. From day 3 or 4 onward, iontophoresis [10]
and low-frequency sonophoresis of vitamin A and C
could maximize the induction of healthy collagen.
Iontophoresis also tends to reduce the swelling of the
skin, which also helps the patient look better sooner.
Low-frequency sonophoresis can be used alone with-
out iontophoresis to enhance penetration of palmitoyl
pentapeptide or other peptides (eg, palmitoyl hexa-
peptide, copper peptides, and so forth), which
also may increase the creation of healthy collagen
and elastin.
After the skin has been needled, it becomes easier
to penetrate, and much higher doses of vitamin A
become available in the depth of the skin. Higher
doses of vitamin A may cause a retinoid reaction
Fig. 16. Mirror image of the right side of the face of a patient
previously treated with extensive silicon injections that
resulted in terrible wrinkling and sagging of her facial skin.
This wrinkling and sagging had improved with suction
aspiration and a face-lift. (Left image) One year after the
face-lift. The skin is still terribly wrinkled and sagging.
(Right image) The patient 1 year after PCI of the whole face
and a scarless malar lift without any skin excision.
Fig. 17. Mirror image of the right breast to show stretch marks before PCI (left image ) and 6 months after PCI (right image). The
stretch marks have become virtually invisible.
even though the milder forms of vitamin A (eg,
retinyl palmitate) are being used. This reaction will
aggravate the pink flush of the skin and also cause
dry, flaky skin. Needling may cause some slight
roughness of the skin surface for a few days, and this
condition is definitely worse when topical vitamin A
is used. The clinician should ignore this and urge the
patient to continue using the topical vitamin A.
Patients usually anticipate that their skin will get red
and do not complain much about that but become
concerned about the dryness. It should be remembered
that the skin has lost the important barrier function of
keeping the water inside the skin. Until this barrier
function is restored completely after a few days, the
skin will feel dry. A hydrating cream or even petro-
latum can be used to soothe the dry sensation.
When the patient has not cleaned the skin thor-
oughly, a fine scab may form on the surface. The
formation of scabs should be discouraged because
they may cause obstruction and the development of
simple milia or tiny pustules. Milia are uncommon but
when they occur, they should be treated by pricking
and draining. Tiny pustules are more common and
usually found in patients treated for acne scars. It is
important to open them early and make sure that the
skin has been cleaned thoroughly and that there is no
serous residue on the surface. When the pustules are
allowed to dry on the skin, they will form thin scabs
that effectively prevent the penetration of the vitamins
necessary for a successful treatment.
The patient should avoid direct sun exposure for
at least 10 days if possible and use a broad-brimmed
hat or scarf to protect the facial skin.
Patients may shocked when they look in the
mirror, but this procedure is a far less shocking
experience than laser resurfacing.
The treatment can be repeated a month later, but
the best interval between treatments is presently
unknown. If a clinician intends to achieve a smooth-
ing comparable to a laser resurfacing, then depending
on the original state, a patient may require three or
even four treatments. The results that are achieved are
not temporary but endure for many years. Again, it
should be emphasized that this progress is utterly
dependent on adequate nutrition for the skin.
Predicted appearance after percutaneous collagen
1. Immediately after procedure: bleeding and
2. Five to 20 minutes after procedure: bleeding
stops quickly; serum oozes from the skin
3. Day 1: bruised and dark purple-red appearance
in light skin; puffy facial appearance; some
bruising, especially close to eyes and in thin-
skinned areas
4. Day 2: red-purple hue on light skin like a
moderate sun burn; bruising, if any, starts to
lighten; swelling may be worse on the second
day in many people, and most people are not
ready to be seen in public at this stage
5. Day 3: appearance still pink, with bruising
getting steadily lighter; swelling reduced;
some people ready to appear in public but
could be conspicuous
6. Day 4 to 6: minimal swelling; bruising will take
a few days to disappear; can use makeup;
patient can appear in public with confidence
with the use of makeup
7. Day 7: in most patients, very few signs are
visible of the procedure. Most patients should
5 and10 days if they deal with people at work
and are sensitive about their own appearance
Fig. 18. Mirror image of the right arm shows wrinkling and loose skin prior to PCI (left image) and tighter skin 4 months after
one session of PCI (right image).
minimally invasive percutaneous collagen induction 61
Note about darker, pigmented skin
Most patients with dark, type IV and V skin will
not show the amount of bruising that Medical Roll-
Cit usually causes. The skin will appear puffy, and
bruising might be visible only in thin-skinned areas
such as around the eyes. Changes are a lot less visible
than in light-skinned individuals. Darker-skinned
patients should protect the skin from exposure to
sunlight and, if necessary, a zinc oxide paste should
be used to ensure ultraviolet light protection. A com-
plication many people fear is the risk of hyper-
pigmentation. Tattoos are rarely hyperpigmented,
even in darker-skinned people. The author has never
seen hyperpigmentation in patients with darker skins
(eg, African, Indian, Malaysian, Chinese, Mediterra-
nean) that have been needled.
Results of percutaneous collagen induction
PCI has been used with success for lower-eyelid
wrinkles (see Fig. 2), upper-lip lines (see Figs. 3
and 4), facial wrinkles (see Fig. 5;Fig. 18), and lax
photo-damaged skin on the arms (see Fig. 7),
abdomen (Fig. 19), and legs. It is also useful for
reducing the appearance of stretch marks (see Fig. 6)
so that they become almost invisible. It is particularly
useful for acne scars and post burn scars. The scars
will flatten and, after a few treatments, the mesh
marks of skin grafts will be less obvious.
Advantages of percutaneous collagen induction
1. PCI does not damage the skin. Histology has
shown that the skin is indistinguishable from
normal skin and that the epidermis may show
more dermal papillae.
2. Skin becomes thicker, with greater than a
400% increase in collagen deposition and
significantly more elastin (Fig. 6).
3. Any part of the body may be treated.
4. The healing phase is short.
5. Compared with laser resurfacing, it is less
expensive and the skin is healthier.
6. May be safely done in people with darker pig-
mented skin, without fear of hyperpigmentation.
7. The skin does not become sun sensitive.
8. Can be done on people who have had laser
resurfacing or have very thin skin.
9. Telangiectasia generally improves probably
because the vessels are ruptured in so many
places that they cannot be repaired.
10. The technique is easy to master using a new
tool that has been specially designed for the
procedure and does not necessarily have to be
done by a plastic surgeon or dermatologist.
11. PCI can even be done using topical anesthesia
for limited areas.
Disadvantages of percutaneous collagen induction
1. Exposure to blood. This procedure is relatively
bloody, much the same as dermabrasion.
2. Although PCI cannot achieve as intense a
deposition of collagen as laser resurfacing, the
treatment can be repeated to get even better
results that will last as long if not longer than
laser resurfacing.
3. Overaggressive needling may cause scarring,
particularly when using a tattoo gun. This
scarring does not seem to occur when using
the special barrel of needles.
4. Herpes simplex is an uncommon complication
and patients are instructed to use a topical
virocidal if they feel the tingling feeling typical
of herpes.
PCI is a simple technique and, with the right tool,
can thoroughly puncture any skin easily and quickly.
Although a single treatment may not give the
Fig. 19. Mirror image of the right side of the abdomen
before PCI (left image) and 4 months after PCI (right image )
showing smoothening of the abdominal skin. A second
session of PCI will smoothen the redundant skin.
smoothing that is seen with laser resurfacing, the
epidermis remains virtually normal. When the result
is not sufficient, treatment can be repeated. The
technique can be used on areas that are not suitable
for peeling or laser resurfacing.
[1] Orentreich DS, Orentreich N. Subcutaneous incision-
less (subcision) surgery for the correction of depressed
scars and wrinkles. Dermatol Surg 1995;21(6):543 – 9.
[2] Fernandes D. Upper lip line treatment. Paper pre-
sented at the ISAPS Conference. Taipei, Taiwan,
October 1996.
[3] Camirand A, Doucet J. Needle dermabrasion. Aesth
Plast Surg 1997;21(1):48– 51.
[4] Fernandes D. Skin needling as an alternative to laser.
Paper presented at the IPRAS Conference, San
Francisco, CA, June 1999.
[5] Fisher GJ, Wang ZQ, Datta SC, et al. Pathophysiology
of premature skin aging induced by ultraviolet light.
N Engl J Med 1997;337(20):1419– 28.
[6] Fisher GJ, Datta SC, Talwar HS, et al. Molecular basis
of sun-induced premature skin aging and retinoid
antagonism. Nature 1996;379(6563):335– 9.
[7] Diaz BV, Lenoir MC, Ladoux A, et al. Regulation
of vascular endothelial growth factor expression in
human keratinocytes by retinoids. J Biol Chem 2000;
275(1):642 – 50.
[8] Varani J, Fisher GJ, Kang S, et al. Molecular
mechanisms of intrinsic skin aging and retinoid-
induced repair and reversal. J Investig Dermatol Symp
Proc 1998;3(1):57 – 60.
[9] Falabella AF, Falanga V. Wound healing. In: Freinkel
RK, Woodley DT, editors. The biology of the skin.
New York: Parthenon Publishing Group; 2001.
p. 281 – 97.
[10] Schmidt JB, Binder M, Macheiner W, et al. New
treatment of atrophic acne scars by iontophoresis with
estriol and tretinoin. Int J Dermatol 1995;34(1):53 – 7.
minimally invasive percutaneous collagen induction 63
... According to him, advantages include preservation of the epidermis, a short healing phase, and the use of local anesthetic alone. [5] Fernandes came forth with percutaneous collagen induction (PCI) therapy as an alternative to laser resurfacing to treat acne scars and wrinkles. According to him, advantages include preservation of the epidermis, a short healing phase, and the use of local anesthetic alone. ...
... We should never damage the epidermis unless the risk of leaving the epidermis intact is greater than the risk of removing it. [5] Dermaroller does not damage the skin or remove the epidermal layer. One single microneedling causes tiny wound in skin and as a result of posttraumatic response platelets are released, which produce a series of growth factors that promote the body's own production of collagen and elastin. ...
... He also suggested that the patients should avoid direct sun exposure for at least 10 days if possible and use a broad-brimmed hat or scarf to protect the facial skin. [5] In our study, we gave icepacks to our patients rolled in sterile gauze piece and asked them to apply for 5-10 min till the bleeding completely stopped. The patients were instructed to avoid sun exposure for 10 days following the procedure. ...
Context: Microneedling therapy is one of the recent advances in treating acne facial scars. Aim: To evaluate the efficacy of microneedling therapy in the treatment of atrophic acne facial scars. Settings and design: A total number of 10 patients between the age group of 20 and 40 years (8 women and 2 men) who complained of acne scars from November 2012 to August 2014 were selected for the study. Subjects and methods: Microneedling therapy was performed following the application of the Eutectic Mixture of Local Anesthetics in an interval of 2 months. All patients underwent three sessions. A follow-up of 2 months after the last sitting was carried out. Statistical analysis: Cochran's Q-paired test, Kendall's W-test, and Pearson's correlation were used for statistical analysis. Results: Patients in our study had three forms of acne scars: box-scar, icepick form, and rolling scars. Patients were told to rate the outcome of the treatment at the end of the follow-up. Three observers randomly selected were shown the pre- and postoperative photographs of the patients to rate the treatment outcome. Statistically there was no interobserver bias. Ninety percent reduction in number of scars and depth of scars was noted at the end of three sittings. The improvement in pigmentation was insignificant. Seventy percent improvement in the skin texture was noted. Nine patients suffered from transient postinflammatory erythema and six patients had postoperative swelling. Conclusion: Microneedling therapy is a safe and effective method of treating acne scars.
... In 2005, the microneedling technique was proposed by Fernandes as a minimally invasive, nonsurgical, and nonablative procedure for facial rejuvenation. 5 A microneedling device (Dermapen; Fig 7-1) is utilized to create controlled minimal skin injury ranging in depths from 0.25 to 2.5 mm. 6 In brief, the technique relies on minimal skin damage causing neovascularization, resulting from needle piercing of the stratum corneum. ...
... The downtime is usually approximately 24 to 48 hours. This method of facial rejuvenation has a much shorter downtime than other comparable methods and a lower risk of side effects such as hyperpigmentation and scarring (when compared to lasers, for instance), making it an ideal treatment choice for all individuals, especially those with thin, sensitive, or darker skin types (skin types III to VI). 5 It is also effective for smokers and other individuals who have been exposed to significant external pollutants. 12 ...
Full-text available
Skin aging is a complex biologic process influenced by many factors, including genetics, cellular metabolism, sun exposure, pollution, stress, and toxins. In 2005, Fernandes proposed the concept of minimally invasive percutaneous collagen induction, or microneedling. As the term implies, a number of microneedles (typically 12) are utilized to perform minimally invasive, nonsurgical, and nonablative therapy of facial tissues. Microneedling relies on the principle of neovascularization that occurs as a result of minimal trauma causing rapid neocollagenesis and tissue repair. This is performed in an automated fashion with a microneedling device—the Dermapen. The Dermapen is an electrically powered medical device that delivers a vibrating stamplike motion to the skin, resulting in a series of microchannels. These channels are then filled with platelet-rich fibrin (PRF), and the device may also be utilized to “push” a product (in this case, PRF) at specific depths within skin to facilitate facial rejunevation via autogenous growth factor release. This chapter reviews the clinical indications and uses of microneedling and provides a protocol depicting its use with PRF.
... Although DMNs have been developed to deliver active compound by overcoming the stratum corneum, hyaluronic acid, the backbone of DMN which is a booster of collagen production, was delivered (21). Because this improves wrinkles, a comparison between the active compound encapsulated in DMNs and the blank DMNs masks the improvement effect generated by hyaluronic acid. ...
... Despite the lower quantity of active ingredient, the skin-improving effects of Ad-DMNs were better than those of the Ad-Cream.DMNs had better drug delivery efficacy than cream formulations because DMNs physically penetrate the skin barrier and directly release the encapsulated drug inside the skin, whereas the cream formulations are applied on skin and only a small amount of encapsulated drug is delivered owing to the barrier presented by the stratum corneum[28]. Moreover, the DMNs have inherent skin-improvement effects through the induction of micro-needling, which leads to a natural wound healing effect on the skin after the activation of collagen production and the improvement of various factors, such as wrinkle and dermal density[21].In the DMN fabrication process, HA was used in the structure of DMN. HA is reported to promote collagen synthesis and partially restore dermal matrix components, thereby relieving wrinkles and improving the conditions of the skin[29]. ...
... Hyaluronic acid provides powerful moisture retention capacity, thus leading to an increase in skin elasticity and volume [16]. Microscopic mechanical stretching of fllers and damage caused by microneedle penetration stimulate the production of more hyaluronic acid and collagen synthesis in particular [17,18]. On these foundations, the addition of more components like ascorbic acid or niacinamide brings broader skin texture and color improvement for HA-DMNs [19,20]. ...
Full-text available
Background. Recently, hyaluronic acid dissolving microneedles (HA-DMNs) have been widely used in antiwrinkle research studies. However, the comparison of HA-DMNs with nonablative fractional laser (NAFL), which is regarded as the gold standard in the treatment of facial wrinkles, is still lacking. Objective. The purpose was to compare the therapeutic effects and adverse effects of HA-DMNs and NAFL on infraorbital wrinkles. Methods. A prospective, randomized, split-face trial was performed with HA-DMNs on one side and NAFL on the other. The wrinkle numbers, photo-numeric scores, and VISIA assessment scores were compared at baseline and 2, 4, 8, and 12 weeks post-treatment. Reflectance confocal microscopy (RCM) was used to monitor collagen fibers. Adverse effects and subjects’ satisfaction scores were evaluated using scales. Results. The final analysis included 28 patients. The wrinkle numbers and photo-numeric scores decreased on both the HA-DMNs side and the NAFL side in week-2, 4, 8, and 12. The VISIA scores decreased on the HA-DMNs side in week-8 and on the NAFL side in week-2. There were no significant differences in these indexes between the two sides. The RCM images demonstrated a similar increase in collagen density on the two sides. Burning, erythema, edema, and crust scores were higher on the NAFL side than on the HA-DMNs side. There was no significant difference in the subjects’ satisfaction scores of the two sides. Conclusion. HA-DMNs are effective treatment options for infraorbital rejuvenation. From the change of wrinkle numbers and scores, HA-DMNs provided comparable efficacy as NAFL in an observation period of 12 weeks. Meanwhile, HA-DMNs offered a more favorable adverse effect profile than NAFL therapy. Mild but persistent pain, erythema, and edema during the HA-DMNs therapy are noteworthy and require improvement.
... It is done by using a sterile dermaroller or dermapen, which is made up of a number of fine and sharp needles that penetrate the skin. Multiple microbruises form in the dermis triggering a complex cascade of growth factors that results in collagen production (5,6) . ...
... 61,62 Microneedling Fernandes was the first to describe percutaneous collagen induction, also known simply as microneedling, as a viable treatment for skin rejuvenation. 63 In this method, a handheld roller or stamp studded with 0.5-to 2.0-mm long needles is applied to the skin to create microscopic punctures in the skin, leading to collagen and elastin production. Numerous studies have demonstrated the clinical efficacy and high safety profile of microneedling for atrophic acne scarring. ...
Full-text available
Abhinav Vempati,1 Crystal Zhou,1 Curtis Tam,1 Jeffrey Khong,2 Aaron Rubanowitz,3 Kevin Tam,1 Sarah Hazany,1 Ruslan Vasilev,1 Salar Hazany1 1Scar Healing Institute, Los Angeles, CA, USA; 2Johns Hopkins School of Medicine, Baltimore, MD, USA; 3Geisel School of Medicine, Hanover, NH, USACorrespondence: Abhinav Vempati, Scar Healing Institute, Los Angeles, CA, USA, Tel +1 424 225 2453, Fax +1 310 571 8435, Email info@shi.orgAbstract: Subcutaneous incisionless surgery, also known as subcision, is a minimally invasive procedure that is commonly indicated for the treatment of atrophic acne scars. In recent years, many new techniques have been developed to maximize results from this procedure. This review article aims to identify an updated list of instruments and combinatorial treatments available for atrophic acne scar patients undergoing subcision. We constructed a comprehensive PubMed search term and performed triple-blinded screening on all resulting studies for mentions of subcision as indicated by acne scarring. Our results show that there are four main categories of subcision tools that are commonly employed to treat atrophic acne scars: needles, cannulas, wires, and blunt-blade instruments. Usage of these devices varies by scar depth, personal preference, and combinatorial treatment options. Overall, subcision is a particularly effective treatment for atrophic acne scars, and there is vast potential for further innovation with this technique.Keywords: subcutaneous incisionless surgery, acne scar, depressed scars, CROSS, Taylor liberator
... Microneedling has shown effectiveness in skin rejuvenation, scar remodeling, melasma, and other pigmentary skin disorders 2,[4][5][6][7][8] . It is achieved by using solid needle pins to puncture the epidermis (or dermis, depending on needle length) which creates microwounds that trigger a downstream wound healing cascade 9 . These microwounds can also serve as microscopic channels for large molecules to overcome the skin barrier and penetrate to deeper layers of the tissue 10 . ...
Full-text available
Microneedling is a popular skin resurfacing and rejuvenation procedure. In order to develop better adjunct products for consumers, there is a scientific need to establish greater understanding of the mechanism in which microneedling stimulates regeneration within skin. The purpose of this study is to develop a physiologically relevant ex vivo tissue model which closely mimics the actual microneedling procedure to elucidate its mechanism of action. In this study, human ex vivo skin was subjected to microneedling treatment and cultured for 6 days. Histological analysis demonstrated that the ex vivo skin was able to heal from microneedling injury throughout the culture period. Microneedling treatment stimulated proliferation and barrier renewal of the skin. The procedure also increased the levels of inflammatory cytokines and angiogenic growth factors in a dynamic and time dependent fashion. The tissue demonstrated hallmark signs of epidermal regeneration through morphological and molecular changes after the treatment. This is one of the first works to date that utilizes microneedled ex vivo skin to demonstrate its regenerative behavior. Our model recapitulates the main features of the microneedling treatment and enables the evaluation of future cosmetic active ingredients used in conjunction with microneedling.
... After the epidermis is physically damaged, platelets and neutrophils are drawn in, and they release growth factors including TGF-alpha, TGF-beta, and platelet-derived growth factor (PDGF), which cause the papillary layer of the dermis to produce collagen and elastin (Fernandes, 2005). Different studies reported that microneedling resulted in clinical improvement in acne scars by occurrence of selective dermal injury that leads to wound healing repair response by increasing the growth cytokines synthesis, collagen and elastin deposition and decreases inflammatory markers (Mujahid et al., 2020). ...
Full-text available
Peyronie’s disease (PD) is a connective tissue disorder resulting from abnormal development of fibrotic and non-expandible thickened scar tissue in the penis. Surgical intervention might lead to other complications, including decreased sensation in the penis, persistent pain after surgery, and less-rigid erections. This study presents the physiotherapeutic assessment and management of a 33-year-old man with erectile dysfunction and impaired penile sensation following reconstructive surgeries of the penis. The patient was given physiotherapeutic interventions including dry needling (DN) and subcision of the scar and stretching exercise of the penis. After the 5th visit, the patient reported improvement in symptoms. This case report suggests that dry-needling and subcision techniques can improve pain and sexual well-being in patients with post-plication surgery problems.
Introduction: Alopecia areata (AA) manifests as patchy hair loss and intralesional corticosteroid (ILCS) is usual therapeutic choice in limited disease. Microneedling is used for uniform delivery of topical agent to relatively larger areas may prove to be more efficacious than traditional ILCS. The present study prospectively compared microneedling to traditional intralesional delivery of triamcinolone acetonide (TA). Materials and methods: Prospective randomized comparative study in 60 patients of AA restricted to scalp not requiring systemic treatment randomly divided into two equal groups. Group 1 patients underwent microneedling with local application of injectable TA and Group 2 patients were given injectable TA intradermally for a total of three sessions at 3 weeks interval. Results: A mean regrowth of 66.36% in Group 1 and 69.75% in Group 2 at week 9 was seen which was comparative with no significant statistical difference between the two groups (P = 0.664). Thirteen patients achieved 100% regrowth at week 9 in Group 1 and 16 patients achieved 50%-99% regrowth in Group 2. Discussion and conclusions: ILCSs have been cornerstone in the treatment of limited AA, but depth of injecting drug cannot be controlled, microneedling whereas is an effective drug delivery system and also causes release of growth factors. In this study, injectable TA used intralesionally and topically with microneedling had nearly similar efficacy in causing regrowth of hair with microneedling resulting in a more uniform but less dense regrowth of hair with lesser adverse effects.
Full-text available
Vascular endothelial growth factor (VEGF) is overexpressed in hyperproliferative diseases, such as psoriasis and cancers, which are characterized by increased angiogenesis. Experimentally, VEGF overexpression can be induced by the treatment of cell cultures and biological tissues with phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Using normal human keratinocytes in conventional cultures and skin grafted onto nude mice in vivo, we show that retinoids can inhibit TPA-mediated VEGF gene induction at the transcriptional level. Because retinoids are biologically active either by interacting with the nuclear retinoic acid receptors or by interfering with the activator protein 1 (AP1) transcription factor, we studied the effect of the retinoic acid derivative CD 2409, which exhibits strong anti-AP1 activity but does not bind to the known retinoic acid receptorsin vitro. The results demonstrate that the inhibition of VEGF expression by retinoids only depends on their anti-AP1 activity and does not require gene transactivation via retinoic acid response elements. Because the VEGF promoter contains four potential AP1 binding sites, we used different promoter constructs to identify the functional site responsible for TPA induction and retinoid inhibition. This site turned out to be localized at position −621 of the 5′ flanking region of the VEGF gene.
Full-text available
Damage to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation, and is believed to be responsible for the wrinkled appearance of sun-exposed skin. We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if imperfectly repaired, would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).
Common treatment of atrophic acne scars consists of invasive methods such as dermabrasion, chemopeeling, or implantation of bovine collagen. In our study a new noninvasive treatment method consisting of local iontophoresis is demonstrated. Local iontophoresis was performed with either estriol--a mainly topically active estrogen--or with tretinoin. Eighteen women were treated with estriol iontophoresis twice weekly for a period of 3 months. In addition to photographic and clinical documentation of the skin, venous blood for determination of serum levels of prolactin and estradiol according to standard radioimmunoassay methods was obtained monthly. Tretinoin iontophoresis was performed according to the same time schedule in 28 patients (19 women and 9 men) with atrophic acne scars. Improvement of acne scars was observed in 93% of patients treated with tretinoin iontophoresis and in 100% of the group treated with estriol iontophoresis. No hormonal changes were noted in the estrogen group. Side effects involving the skin appeared in the tretinoin group in 4 cases and consisted of increased dryness and of retinoid dermatitis. Both treatments were shown to be clinically effective in decreasing acne scars and persistence of effects. This promising new therapeutic approach may thus replace invasive treatment methods in many patients.
A new method of subcuticular underming for the treatment of depressed cutaneous scars and wrinkles is introduced. To define the newly coined term "Subcision" and to describe this minor surgical procedure for treating depressed scars and wrinkles. A tri-beveled hypodermic needle is inserted through a puncture in the skin surface (hence, "incisionless" surgery), and its sharp edges are maneuvered under the defect to make subcuticular cuts or "-cisions." The depression is lifted by the releasing action of the procedure, as well as from connective tissue that forms in the course of normal wound healing. This technique is useful in treating a variety of cutaneous depressions, including scars and wrinkles.
In this article we describe a technique of needle dermabrasion (tattoo without pigment) used to improve achromic, hypertrophic, and unsightly scars. It is simple, safe (no complications), and it gives us consistently good results.
Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.
Past studies have shown that topical treatment of suntxposed skin with all-trans retinoic acid improves the clinical and histologic appearance of the skin. This is mociated with a reduction in matrix metalloproteinase elaboration and with expression of a newly synthesized collagenous matrix. Whether retinoid therapy might have a similar impact on the appearance of intrinsically aged skin is not known. This study, using human skin in organ culture and epidermal keratinocytes and fibroblasts in monolayer culture, show that retinoic acid stimulates growth of both keratinocytes and fibroblasts and stimu-lates extracellular matrix production by the fibroblasts. Adult skin from sun-exposed and sun-protected sites responds equally well to retinoic acid, whereas neonatal skin is much less responsive under the same conditions. The implications of this are (i) that retinoids may be able to repair intrinsically aged skin as well as photoaged skin, and (ii) that retinoids modulate human skin cell function in a manner that is age-related, and not simply a response to photodamage. Journal of Investigative Dermatology Symposium Proceedings 3:57-60, 1998
Skin needling as an alternative to laser. Paper presented at the IPRAS Conference Pathophysiology of premature skin aging induced by ultraviolet light
  • D Fernandes
  • Fisher Gj
  • Zq Wang
  • Datta
  • Sc
Fernandes D. Skin needling as an alternative to laser. Paper presented at the IPRAS Conference, San Francisco, CA, June 1999. [5] Fisher GJ, Wang ZQ, Datta SC, et al. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 1997;337(20):1419 – 28.
Wound healing The biology of the skin
  • Falabella Af
  • Falanga
Falabella AF, Falanga V. Wound healing. In: Freinkel RK, Woodley DT, editors. The biology of the skin. New York: Parthenon Publishing Group; 2001. p. 281 – 97.
Molecular basis of sun-induced premature skin aging and retinoid antagonism
  • Gj Fisher
  • Datta
  • Sc
  • Talwar
  • Hs
Fisher GJ, Datta SC, Talwar HS, et al. Molecular basis of sun-induced premature skin aging and retinoid antagonism. Nature 1996;379(6563):335 – 9.