New Developments for

Fractional CO2 Resurfacing

for Sk in Rejuvenat io n an d Sc ar
Reduction
Matteo Tretti Clementoni, MDa,*, Valerio Pedrelli, MDa,
Giovanna Zaccaria, MDa, Paolo Pontini, MDa, Laura Romana Motta, MDa,
Ernest A. Azzopardi, MD, MSc Surg PhD, MRCSEd, MRCSEng (Ad Eudem), Dip spec
laser, FRSB, FRCSEd (Plast)a,b

KEYWORDS
 Fractional CO2  Resurfacing  Laser-assisted drug delivery  Scars

KEY POINTS
 Fractional CO2 resurfacing offers a very good outcome with a short downtime and a very high safety
profile.
 Best rejuvenation outcomes can be achieved when the procedure is customized on each patient
affecting different layers of the skin.
 Fractional CO2 can determine a significant change in dermal architecture of severe burn scars,
improving function and appearance of burn patients.
 The laser-assisted drug delivery induces a great and uniform absorption of drugs inside the skin.

INTRODUCTION: THREE SIGNIFICANT presenting this kind of severe scars. Finally, use of
DEVELOPMENTS IN RECENT YEARS ablative fractional lasers to faciltiate trans-dermal
drug delivery (laser-assisted drug delivery, or
The drive to attain cosmetic facial improvement LADD) opened up a new dimension in personalised
with rapid recovery and minimal risk has galvanized medicine, and precision therapeutics. This laser-
laser treatments. The introduction, 15 years ago, of assisted drug delivery allows physicians to deliver
nonablative fractional devices and of ablative frac- drugs, such as triamcinolone, 5-fluorouracil, botuli-
tional devices immediately thereafter, provided num toxin, and poly-l-lactic acid (PLLA), at a pre-
laser specialists with the potential for a safe and cise depth inside the skin. These 3 developments
significantly effective cosmetic outcome. A few have a common denominator: the principle of the
years later, the realisation that the same devices customization of the procedure. The next para-
can safely and effectively improve function and graphs describe how the authors use an ultrapulse
appearance of severe burn scars, produced a CO2, customizing the procedures to each patient
step-change in management of secondary burn and the principles and the rationale behind them.
reconstruction. The possibility of adding laser treat-
ments to the classical surgical approaches in
restoring function and appearance of severe burn The Device and the Settings
patients gave the opportunity to the laser operators The authors use a radiofrequency excited ultra-
[Link]

to effectively improve the quality of life of patients pulse CO2 laser (UltraPulse Encore; - Lumenis

Ernest Azzopardi’s research is currently supported by the Dowager Eleanor Peel Foundation Trust.
a
Laserplast SrL StP, Piazza Eleonora Duse 2 Milano, Republic of Italy; b R&D Department, Swansea Bay Univer-
sity Health Board and the Welsh Centre for Burns and Plastic Surgery, Moriston Hospital, Swansea SA6 6NL,
United Kingdom
* Corresponding author.
E-mail address: mtretti@[Link]

Facial Plast Surg Clin N Am 28 (2020) 17–28

[Link]
1064-7406/20/Ó 2019 Elsevier Inc. All rights reserved.
18 Clementoni et al

Ltd, Yokneam, Israel) with a pulse duration around for ligament, and skin laxity and superficial dam-
500 microseconds. It can deliver 225 mJ of energy age owing to the UV irradiation. Although volume
having 240 W of power to tissue. The decision to and shape of soft tissues of the face can only mini-
use an ultrapulse CO2 depends on the features mally be affected by a CO2 fractional resurfacing,
this device offers in the interaction laser/tissue. superficial photodamage can be effectively
With a short-pulse duration, the collateral thermal treated. The superficial photodamage consists of
damage is minimal and the downtime is very short. wrinkles, lentigines, sun spots, and a wide sugges-
The ablation threshold of an ultrapulse CO2 is 3 tion of yellowness and grayness of the skin. In a
times lower than a continuous wave (CW) CO2 schematic way and using a sketch, the photodam-
(which means that 3 times less energy must be age can be represented as in Fig. 2.
applied to start to ablate skin). In a hypothetical The customized plan is obtained by marking all
comparison between an ultrapulse CO2 and a the wrinkles and the biggest lentigines (Fig. 3)
CW device (where the pulse duration is longer with a skin marker. A numbing cream (7% lido-
than 2 milliseconds), it can be demonstrated that caine–7% tetracaine) is applied on the skin for
if the same spot size and the same energy with 1 hour (Pliaglis; Galderma, Uppsala, Sweden)
the ultrapulse CO2 are used, the ablation channel and then carefully removed with dry gauze. A
will be deeper, the ablated volume will be larger, nonalcoholic disinfectant is then passed on the
and the collateral thermal damage will be lower1,2 skin without removing the marks. The procedure
(Fig. 1). is then performed with the help of a device that
The device has 2 hand pieces. One hand piece emits cold air ( 20 C; Cryo 6; Zimmer, Neu-Ulm,
is called CPG (computer pattern generator) and Germany) to make it more comfortable for the pa-
creates ablation of 1300 microns of diameter, tient (see Fig. 3).
whereas the second is a microscanner that cre-
ates ablation of only 120 microns of diameter. THE TECHNIQUE
CPG settings are described by energy (mJ), fre-
quency (Hz), and 3 numbers: the first indicates The multilayer technique can be divided into 5
the shape pattern (line, hexagon, square, and so steps:
forth); the second indicates the shape dimension 1. Step 1: Use the microscanner hand piece. Us-
(the higher the number, the higher the dimension), ing a short linear shape, the authors follow
while the third indicates the microshots density. each wrinkle, trying to hit the base of it. They
The microscanner settings are described by en- use 15 to 40 mJ depending on the skin thick-
ergy (mJ), frequency (Hz), and, as before, shape, ness (the thicker the skin, the higher the energy)
dimension, and density of the microshots. and a density of 10%. The frequency is always
300 Hz. The aim of this pass is to deliver a large
Fractional Skin Resurfacing for Rejuvenation: amount of heat at the base of each wrinkle to
The Multilayer Technique obtain an important new collagen production
exactly where needed (Fig. 4).
Aging skin processes are complex and include
2. Step 2: Again use the microscanner hand
bone resorption, fat resorption, soft tissue ptosis
piece. Using a rectangular shape, the authors
decrease the energy (15–25 mJ), but they in-
crease the density to 15% to 20%. As before,
the authors follow the route of each wrinkle
(Fig. 5). The aim of this pass is to obtain
shrinkage of the wrinkle. If they have wrinkles
very close to each other, the authors use a
square shape, and with the same settings of
energy and density, they cover all the affected
area.

Fig. 1. Applying the same energy on the same spot

size, a CO2 laser with a short-pulse duration (A) will
determine a deeper penetration, a large volume abla-
tion, and (B) less thermal damage than a CO2 laser Fig. 2. The 2 major features of aging skin: wrinkles
with a long-pulse duration. and lentigines.
 New Developments for Fractional CO2 Resurfacing 19

Fig. 3. The preoperative marking.

3. Step 3: Again, using the microscanner hand energy (30–40 mJ) but very high frequency
piece and using a square shape with a medium (350 Hz) and very high density (density 9). This
amount of energy and density (15–20 mJ and way the authors are not doing a “fractionated
10%–15% of density), the authors treat both procedure,” but they are trying to ablate all pig-
cheeks. The aim of this pass is to obtain a tight- mented lesions using a nonpigmented specific
ening effect of the areas where the laxity of soft device. These pure ablative settings (very low
tissues is more visible (Fig. 6). energy with high frequency and high density)
4. Step 4: Using the CPG scanner and using a cir-
cular shape, the authors remove all lentigines
and pigmented lesions. They use very low

Fig. 4. Step 1 of the multilayer technique. Fig. 5. Step 2 of the multilayer technique.
20 Clementoni et al

Fig. 6. Step 3 of the multilayer technique.

allow the authors to ablate the lesions, deliv- PRETREATMENT AND POSTTREATMENT
ering as little heat as possible3 (Fig. 7). REGIMEN
5. Step 5: The last pass is performed using the
CPG hand piece. The authors use a large hex- The authors exclude patients from the treatment
agonal shape with 125 to 150 mJ of energy, who present the following: (i) pregnancy; (ii) lacta-
125 to 150 Hz of frequency, and density of 3 tion; (iii) history of keloids; (iv) history of severe her-
(covering this way 82% of the surface) pes infections; (v) likelihood of poor compliance;
(Fig. 8). They cover the full face, and for 1 cm (vi) presence of an active infectious disease or
below the jaw line, the authors reduce the en- other inflammatory or neoplastic skin diseases;
ergy to 70 to 80 mJ. These different settings (vii) psychiatric diseases; and (viii) unrealistic ex-
are to attempt to feather the result, to avoid pectations. Starting the night before the treatment,
visualizing a clear, sharp line between the all patients were treated with oral cefixime (400 mg
treated and nontreated areas. The same results every day for 5 days), valacyclovir (1000 mg, 2
can be obtained simply by inclining the hand every day for 14 days), and fluconazole (100 mg
piece at 45 and transforming the microshot /day for 8 days). Patients with dark skin type or pa-
from circular to oval. tients prone to a postinflammatory hyperpigmen-
tation are treated for 5 weeks before the
treatment with modified Kligman-Willis formula
(tretinoin, hydroquinone, vitamin C and hydrocorti-
sone in a water-based cream). These small fine
crusts must not be removed because they can
be used as a completely biocompatible wound
dressing. Just after the end of the procedure,
wet cold gauzes are applied to the treated surface,
kept moist and cool using cold saline solution.
Twenty to 30 minutes after the treatment or when
the pain or burning sensation eased off, a thin layer
of an ointment (Aquaphor; Eucerin, Collegno, Italy)
was applied. Cleansing was allowed only with a
gentle cleanser starting from 36 hours after the
Fig. 7. Step 4 of the multilayer technique.
treatment. Before leaving the office, all patients
 New Developments for Fractional CO2 Resurfacing 21

Fig. 8. Step 5 of the multilayer technique.

are instructed to repeatedly apply the ointment for The adverse events are usually rare and transi-
the next 3 to 5 days and are advised against pick- tory (the authors observed only a few cases of pro-
ing or scrubbing the skin. All patients are also longed erythema and hyperpigmentations, which
strictly instructed to repeatedly apply topical sun- disappeared spontaneously in a maximum of
block preparations for 60 days starting on the day 4 weeks). Severe adverse events, such as scars,
of the disappearance of the small crusts. The au- infections, or hypopigmentations, have never
thors also ask patients not to go directly into the been observed.
sun (beach vacation or mountain vacation) for
2 months after the procedure. The downtime AN OVERVIEW ON THE SCIENCE BEHIND THE
(calculated as the time needed for the crusts to ULTRAPULSE FRACTIONAL CO2 PROCEDURE
disappear) is usually 5 to 7 days. After this interval ON SEVERE BURN SCARS
of time, the patient will present a uniform erythema
that will disappear in a couple of weeks. Patients The exact mechanism of action at the base of the
with dark skin or patients prone to develop postin- outcomes that can be observed after an ultrapulse
flammatory hyperpigmentation will start to apply fractional CO2 procedure has yet to be fully under-
the Kligman-Willis modified formula (previously stood. Creating thousands of thin, deep holes in-
described) for 6 to 8 weeks. side the burn scar, 2 immediate mechanical
results can be achieved. With a spot size of
RESULTS 120 mm and a maximum energy of 150 mJ, the
SCAARFX mode (synergistic coagulation and
The degree of photoaging and the efficacy of the ablation for advanced resurfacing) allows attain-
treatment can be evaluated using a 5-point scale ment of a penetration depth of 4.5 mm. The
based on the suggestion of Dover and col- SCAARFX mode (synergistic coagulation and
leagues.4 A global score can be recorded as well ablation for advanced resurfacing) allows attain-
as that of 5 photodamage variables: fine lines, ment of a penetration depth of 4.5mm. Therefore,
mottled pigmentation, sallow complexion, tactile each microbeam ablates a volume of 0.05 mm3 of
roughness, and coarse wrinkles. Based on this 5- scarred tissue, and calculating this ablation for
point scale, the authors demonstrated5,6 that the thousands of times, a great amount of scarred tis-
technique with the customization of the procedure sue can be removed. At the same time, the thin
offers very good outcomes (Fig. 9) and that the re- columns break the disorganized thick collagen fi-
sults can be considered stable 24 months after the brils that create the contracture. The mechanical
procedure (Fig. 10). forces that create the contracture are immediately
22 Clementoni et al

Fig. 9. Result of a fractional resurfacing of the face using the multilayer technique (8-month follow-up).

Fig. 10. Result of a fractional resurfacing of the face (2-year follow-up).

 New Developments for Fractional CO2 Resurfacing 23

interrupted, and the body has the ability to heal in a The drugs are the same of those described before.
more organized fashion. We are convinced that Procedures on small areas (up to 500 cm2) can be
the ablation of the scar tissue as well as the inter- performed by applying a topical anesthetic cream
ruption of the contraction forces are the explana- (the authors use Pliaglis, Galderma, which is
tion why patients refer, immediately after the composed by lidocaine 7% and tetracaine 7%)
procedure, a relaxation of the scars the patients and using a cold air chiller device (Cryo 6; Zimmer)
refer immediately after the procedure. The ablation to attempt to reduce the discomfort of the patients
of the scar tissue and the interruption of the during the procedure. An ultrasound evaluation of
contraction forces are not the only aspect involved the scar establishing the thickness in the different
in the final relaxation of a scar. The result thus ob- areas of it can be very helpful in deciding on the
tained could be frustrated by a subsequent further energy that could be applied on different areas.
healing process. Interacting with the skin, the laser
energy also determines heat release. A controlled THE PROCEDURE
(this is why a very short-pulse duration CO2 laser
is preferable to longer-pulse duration devices) All scars can clinically present thick areas, atro-
heat diffusion induces a molecular cascade, phic areas, and many superficial irregularities. All
including heat-shock proteins and matrix metallo- these aspects must be addressed during each sin-
proteinases (MMP) as well as inflammatory pro- gle procedure. There also are no standardized set-
cesses that lead to a rapid healing response and tings because scars are extremely different
prolonged neocollagenesis with subsequent regarding thickness, pliability, and superficial fea-
collagen remodeling. Studies on the effect of frac- tures. A few general rules should be always, in
tional CO2 laser on scar have shown alterations of the authors opinion, followed:
types I and III procollagen; MMP-1; transforming  Ablated microcolumns must penetrate the full
growth factor-b2, -b3, and -bFGF, and miRNAs thickness of the scar without getting to the
miR-18a and miR-19a expressions.7 In a subse- subcutaneous tissue.
quent study, gene expression profiling revealed  The higher the energy applied, the lower the
induced expression of Wnt5a, CYR61, and density of the microcolumns.
HSP90 in human skin during the early remodeling  Oppositely, the lower the energy applied, the
phase after fractional CO2 laser treatment.8 All higher the density of the microcolumns.
these proteins play an important role in collagen  Pinpoint bleeding can be considered a good
remodeling. It was demonstrated that after an clinical end point.
ultrapulse fractional CO2 procedure, there is an  A visible contraction of the scar tissue during
inversion of the ratio between collagen type I and the procedures should be carefully avoided.
collagen type III. Although some MMPs’ produc-
tion is upregulated, profibrotic growth factors are Our protocol can be divided into three distinct
downregulated. Ultrapulse fractional CO2 proced- steps for simplicity.
ures also produce a dermal architecture change. The authors start the laser session (step 1;
Collagen fibers are less thick, and the classical or- Fig. 11) by treating the thicker areas/bands using
ganization parallel to the surface is much less the microablation hand piece. It creates microcol-
evident. Collagen fibers are more chaotic (more umns with a diameter of 120 mm and of variable
similar to normal skin), and also the vascularity is penetration according to the energy. An energy
different. After the procedure, there are more ves- of 150 mJ creates a penetration of around
sels of small calibers oriented vertically.9 4.0 mm, whereas an energy of 100 mJ creates a
penetration of 2.6 mm.
PREOPERATIVE EVALUATION AND SETUP The proper energy level to apply is the one that
is able to create ablated columns of depth slightly
All scarring areas should be carefully observed, below the thickness of the scar. Using magnifica-
and patients should be forced to perform move- tion lenses, the authors observe the interaction of
ments pointing out eventual retractive bands. A the laser with the scar during the first couple of
careful marking of the entire region that will be shots. If a contraction of the tissue is observed,
treated with a skin marker will allow for the proced- the energy level will be reduced. The correct
ure to be performed faster. Retractive bands as threshold of energy to apply is the one that,
well as atrophic areas must be marked. The au- impacting the skin, creates a column of ablation
thors do not prescribe any prophylactic drugs if without any contraction (or creates a minimal
small areas will be treated, whereas huge areas contraction). Pinpoint bleeding is also a second
require, in the authors’ opinion, an antiviral, an good end point to achieve. Very thick scars are
antibiotic, and an antifungal prophylactic therapy. usually treated with an energy of 150 mJ and a
24 Clementoni et al

Fig. 11. Step 1 of the treatment of atrophic (left) and thick scars (right).

density of 1%, whereas atrophic areas can be very low energy (30–50 mJ), very high frequency
treated with an energy of 30 to 35 mJ and a density (350–400 Hz), very high density of microbeams
of 5% to 10%. The authors suggestion is to always (very high density with an overlap of more than
change the energy level according to the skin 50%), and a very small hexagonal spot.
reaction. With these settings, the authors sculpt all super-
The deep previous procedure is followed by a ficial irregularities they can observe. The correct
much more superficial one (step 2; Fig. 12). end point is to observe a white ablation of the sur-
The authors use the CPG hand piece, applying face. Brown and dark-brown color must not be

Fig. 12. Step 2 of the procedure. Using low energy and high frequency and density, all superficial irregularities
are treated.
 New Developments for Fractional CO2 Resurfacing 25

Fig. 13. Step 3 of the procedure. A conventional fractional procedure is performed on the full scarred area.

observed (brown and dark brown means deeper function in burn patients. Fractional CO2 treatment
penetration and more release of heat), and if this induces also strong improvements in the patient’s
happens, the energy must be reduced. quality of life, and although it does not replace
At the end of the procedure, the authors cover reconstructive surgery, it may well decrease the
the full extent of the scarred area (step 3; extent of subsequent surgical procedures and pre-
Fig. 13) using the same hand piece used in step pares the scar for an optimal outcome.
2 but modifying the settings. They increase to the
maximum the dimension of the shot, increase the
POSTOPERATIVE MANAGEMENT
energy to 125 to 150 mJ, reduce the density using
coverage of around 80%, and reduce the fre- Immediately after the laser procedure, the entire
quency to 125 to 150 Hz. This pure fractional treated area is covered with wet cold sterile gauzes.
pass has the aim of obtaining a better and uniform A nurse applies drops of cold saline solution on the
superficial appearance. gauzes every 3 to 5 minutes to keep them wet. The
Since 2009, we started to treat patients with same nurse continues to use the cold air chilling de-
mature scars (older than 2 years without evidence vice on the full treated area for 5 to 10 minutes after
of evolution). However, our practice has now the procedure. When the pain and the burning
changed to treating patients as soon as possible af- feeling disappears (10–20 minutes after the pro-
ter the acute burn phase. Our combined experience cedure), the wet gauzes are removed and a silicone
strongly suggests that the fractional Co2 laser pro- gel (Stratamed; Stratpharma, Basel, Switzerland) is
motes a normalisation of the healing process, when applied on the full area. The patient is instructed to
laser is applied close to naturally remodelling apply a thin layer of the same cream at least 2 times
wounds. Conseqently our practice has change to per day for the next 4 to 7 days (or until all crusts
treating patients as soon as possible after the acute disappear) and to have a shower the evening of
burn phase.10–12 the day after the procedure (a gentle cleanser is
The authors cannot say how many sessions are allowed). Finally, the patient is instructed not to
required to obtain a very good result (Figs. 14 and expose the treated area to UV rays and to apply
15), but are convinced that a good outcome can an SPF 501 at least every 4 hours when outside
be achieved just after the first session, but also for the 2 months after the procedure.
that more sessions can obtain a better result.
The authors clinical results confirmed what was
ADVERSE EVENTS
already published,7,13–33 allowing them to affirm
that lasers may disrupt old algorithms on scar The authors believe that proper preparation as well
treatments and reset their expectations of what as optimal postoperative procedures can reduce
can be achieved, in terms of restoring form and the incidence of adverse events. Major adverse
26 Clementoni et al

Fig. 14. A severe acid burn (A) before and (B) after 3 sessions of treatment.

Fig. 15. A severe acid burn of the right hand (A) before and (B) after 3 sessions of treatment.
 New Developments for Fractional CO2 Resurfacing 27

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