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Improving the outcome of fractional CO2 laser resurfacing using a probiotic

skin cream: Preliminary clinical evaluation

Article  in  Lasers in Medical Science · July 2016

DOI: 10.1007/s10103-016-2024-6

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Improving the outcome of fractional CO2
laser resurfacing using a probiotic skin
cream: Preliminary clinical evaluation

Giovanni Zoccali, Benedetta Cinque,

Cristina La Torre, Francesca Lombardi,
Paola Palumbo, Lucia Romano,
Antonella Mattei, et al.
Lasers in Medical Science

ISSN 0268-8921

Lasers Med Sci

DOI 10.1007/s10103-016-2024-6

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 Author's personal copy
Lasers Med Sci
DOI 10.1007/s10103-016-2024-6

ORIGINAL ARTICLE

Improving the outcome of fractional CO2 laser resurfacing

using a probiotic skin cream: Preliminary clinical evaluation
Giovanni Zoccali 1 & Benedetta Cinque 2 & Cristina La Torre 2 & Francesca Lombardi 2 &
Paola Palumbo 2 & Lucia Romano 1 & Antonella Mattei 3 & Gino Orsini 1 &
Maria Grazia Cifone 2 & Maurizio Giuliani 1

Received: 20 November 2015 / Accepted: 4 July 2016

# Springer-Verlag London 2016

Abstract As known, fractional CO2 resurfacing treatments
are more effective than non-ablative ones against aging signs,
but post-operative redness and swelling prolong the overall
downtime requiring up to steroid administration in order to
reduce these local systems. In the last years, an increasing
interest has been focused on the possible use of probiotics
for treating inflammatory and allergic conditions suggesting
that they can exert profound beneficial effects on skin homeo-
stasis. In this work, the Authors report their experience on
fractional CO2 laser resurfacing and provide the results of a
new post-operative topical treatment with an experimental
cream containing probiotic-derived active principles poten-
tially able to modulate the inflammatory reaction associated
to laser-treatment. The cream containing DermaACB
(CERABEST™) was administered post-operatively to 42
consecutive patients who were treated with fractional CO2
laser. All patients adopted the cream twice a day for 2 weeks.
Grades were given according to outcome scale. The efficacy
of the cream containing DermaACB was evaluated comparing
the rate of post-operative signs vanishing with a control group
of 20 patients topically treated with an antibiotic cream and a
hyaluronic acid based cream. Results registered with the ex-
perimental treatment were good in 22 patients, moderate in 17,
* Maurizio Giuliani
maurizio.giuliani@cc.univaq.it
1
Department of Life, Health & Enviromental Sciences, Plastic and
Reconstructive Surgery Section, University of L’Aquila,
67100 L’Aquila, Italy
2
Department of Life, Health & Enviromental Sciences,
Immunopathology Section, University of L’Aquila,
67100 L’Aquila, Italy
3
Department of Life, Health & Enviromental Sciences, Statistics and
Epidemiology Section, University of L’Aquila, 67100 L’Aquila, Italy
and poor in 3 cases. Patients using the study cream took an
average time of 14.3 days for erythema resolution and 9.3 days
for swelling vanishing. The post-operative administration of
the cream containing DermaACB induces a quicker reduction
of post-operative erythema and swelling when compared to a
standard treatment.
Keywords CO2 laser . Fractional resurfacing . Inflammatory
reaction . Probiotics
Introduction
Skin mirrors the first signs of natural aging and the main-
tenance or the improvement of its quality have gained
particular attention. Understanding the mechanisms un-
derlying skin aging is of great importance in order to
use proper and safe intervention modalities. Aging of
the skin is a composite of actinic damage, chronologic
aging and hormonal influence [1, 2]. All these aspects
conduce to the failure of tissue cellularity and disorgani-
zation of collagen fibers [3]. The purpose of the modern
technique of skin rejuvenation is to reactivate the collagen
metabolism and reorganization to improve the skin quali-
ty. The ablative CO2 laser resurfacing became the most
popular treatment in skin rejuvenation [4, 5], clinically the
skin looks smoother and tighter during healing process
due to superficial epidermal layer removal and shrinkage
of collagen [6]. The procedure might present several side
effects; excessive ablation and thermal damage are re-
sponsible for scarring or hypopigmentation jointly to per-
sistent erythema and swelling after treatment [4]. To re-
duce side effects and to improve the patient outcome, a
new theory governing the laser-tissue interaction was in-
troduced: fractional phothermolisis (FP). The concept of
 Author's personal copy
FP revolutionized laser surgery by enabling the delivery
of dermal coagulative injury without consequent epider-
mal damage. In other word, from the healthy tissue, sur-
rounding the areas of interaction defined as microthermal
zone, fibroblasts migrate into the treated dermis, and fa-
cilitate collagen remodeling allowing to achieve the same
result of past technology reducing the healing time [4].
Thus, fractional CO2 resurfacing treatments are more ef-
fective than non-ablative ones against aging signs, but
post-operative redness and swelling prolong the overall
downtime requiring up to steroid administration in order
to reduce these local inflammatory reactions. These find-
ings often induce the patient to refuse the treatment [7–9].
The skin microflora plays also a significant role in com-
petitive exclusion of pathogens during the infection and in
the processing of skin proteins, free fatty acids and sebum
and an alteration of its composition has a role in several
dermatologic diseases such as atopic dermatitis and acne
[10]. In the last years, an increasing interest has been fo-
cused on the possible use of ingested probiotics for treating
inflammatory and allergic conditions being specific strains
able to modulate the immune system at the local and sys-
temic levels [11]. Arck et al. [12] have hypothesized a new,
unifying model i.e., gut–brain–skin axis, suggesting that
modulation of the microbiome by deployment of probiotics
can exert profound beneficial effects on skin homeostasis,
skin inflammation, hair growth, and peripheral tissue re-
sponses to stress. Our previous studies reported that the
topical application of a sonicated Streptococcus
thermophilus preparation in healthy as well as aged sub-
jects induced a significant increase of ceramide levels im-
proving lipid barrier, resulting in a prompt increase in
water-holding capacity after application of the experimen-
tal cream [13, 14]. Unfortunately, the above cream has nev-
er been further developed due to the very poor stability of
the product and bad smell after few weeks, even if main-
tained refrigerated. No skin product with probiotic compo-
nents is available due to the poor compatibility between
bacteria and components to be used in the production of
the skin preparations. All the published studies have been
carried out with creams where the bacterial components
were added at the moment and to be used within few days.
Consequently, there are very few studies pursuing on top-
ical probiotic approach for microflora-related and non-related
skin disorders and no one after laser procedure [15–17].
In this study, the Authors describe their experience in frac-
tional CO2 laser resurfacing and suggest a new post-operative
treatment consisting on topical application of a new dermato-
logical cream containing probiotic-derived active principles
(DermaACB) focusing the attention on the post-treatment er-
ythema and swelling vanishing. The rationale of this research
is intimately connected to the necessity of downtime reduction
in outpatient treatments.
Lasers Med Sci
Materials and methods
Patients’ selection
Between January 2015 and May 2016, 62 consecutive patients
with aged skin were treated with fractional CO2 laser at our
LASER center. Age of the patients ranged between 32 and
68 years. The diagnosis of patients was based on physical exam-
ination following the Rubin photoaging classification. 42 pa-
tients were treated with an new dermatological cream containing
probiotic-derived active principles (DermaACB) as below de-
scribed. The control group was created collecting 20 patients
with a superimposable age and clinical features when compared
to treated patients [Table 1]. The treated aged skin features were
located predominantly on the face and hands, and were: kerato-
sis, rhytides, shallowness and irregularities in skin thickness and
texture [Table 2].
Laser treatment protocol
The fractional CO2 laser device (SmartXide DOT, DEKA me.la
S.r.l., Calenzano-Florence. Italy) is composed of two different
handpieces: a surgical probe and a scanner system. Saline so-
lution washout was performed before laser exposure, then the
proper machine’s setting was costumized to the individual’s
phototype, clinical defect’s characteristics and localization
[Table 3]. The surgical handpiece is generally preferred for
localised lesions; in these cases the energy supply starts from
the central portion towards the margin in circular shape move-
ments. The laser exposition was then repeated using a lower
intensity in order to homogenise the result. The scanner system
is required in full-face treatments to guarantee a uniform energy
supply. As protocol we treated the entire cosmetic unit in order
to achieve a better outcome, reducing the evidence between
treated and non-treated area. Each area was always exposed
twice to the laser energy passing the scanner in vertical direction
the first time and then in horizontal way. Spots overlapping
should be avoided. After each exposition a saline washout
was administered. During treatments a vacuum system was
used to take the laser’s smoke off. The number of laser sessions
ranged between 1 and 4 at interval of 2–3 months; all treatments
didn’t request any kind of local anaesthetics or systemic seda-
tion. Post-operative therapy of experimental group was based
on application of DermaACB cream on treated area twice a day
Table 1 Patients
distribution according to Rubin’s Control n DermaACB
Rubin’s classification Level (%) cream n (%)
I 6 (30.00) 13 (30.95)
II 3 (15.00) 5 (11.90)
III 11 (55.00) 24 (57.14)
χ2 test for trend: p value = 0.939
 Author's personal copy
Lasers Med Sci

Table 2 Type of treated defect analyzed the effect of the DermaACB containing cream on
Defect Control n (%)* DermaACB swelling and erythema.
cream n (%)* The grade of improvement was calculated using a comput-
er graphic program by pictures overlapping (Anthology -
Perioral wrinkles 4 (8.33) 8 (8.42) DEKA me.la S.r.l., Calenzano-Florence, Italy).
Irregularities in skin texture 16 (33.33) 29 (30.53) In order to assess the efficacy of the DermaACB containing
Hypermelanosis of the face 12 (25.00) 24 (25.26) cream, the results were compared with those obtained with the
Hypermelanosis of the hand 2 (4.17) 4 (4.21) control group. For each one the result was graded as good,
Periocular rhytides 8 (16.67) 18 (18.95) moderate or poor [Table 4]. The patient’s opinion on result
Dull rough skin 6 (12.50) 12 (12.63) was also recorded.
* some patients presented more than one defect
χ2 test: p value = 0.999
Statistical analysis

for 2 weeks. In the control group, topical antibiotic cream
(Gentamicine sulphate cream 0.1 %) was administered three
times a day for 3 consecutive days, and a hyaluronic acid based
cream (Ialuset, IBSA bouty – Milan – Italy) was than applied
twice a day for others 15 days.
Dermatological cream
DermaACB component has been supplied by Mendes SA,
Lugano, Switzerland. DermaACB was mixed with 20 ml of base
cream containing the following components: demineralised wa-
ter, imidazolidynil urea, trietanolamine, transcutol, glycerol,
vaselin oil, vitamin E acetate, polyacrylamide, C13- C14 iso-par-
affin, Laureth-7, methyl gluceth-20, Fenotan, EDTA, methyl-
buthyl-ethyl-propyl-paraben mix, carbomer, bensil dm 350, per-
fume (CERABEST™). In our protocol, a sterile saline solution
was used to clean the treatment area and CERABEST™cream
was applied. Then the patient continued to use the experimental
cream twice a day for 2 weeks.
Clinical evaluation
All patients had follow-up check at 7, 15 and 30 days after
treatment’s ending. We took photos of the patients before the
first treatment and at every following check. During each fol-
low up visit, three researchers external from the study give
grades according to an outcome scale and the average point
was considered as final score [Table 4].
Then, the outcome scale was composed of two parts. The
first part investigated the clinical results, whereas the second
Table 3 Fractional CO2
laser device setting (the Parameter Range
choice was secondary to
defect and phototype) Power 8–24 (W)
Spacing 200–1000 (μm)
Permanence time 500–1200 (μs)
Scan modality smart track
Stack 1 Results
Descriptive analyses were performed to illustrate the charac-
teristics of the two groups. Frequencies and percentages were
calculated for discrete and nominal values, while quantitative
variables were evaluated using means ± standard deviations
(SD). The Wilcoxon Mann–Whitney test was used to examine
differences between mean values and Frequency differences
between the groups were calculated using the χ2 test and χ2
test for trend for ordinal variables. Statistical tests were bidi-
rectional and used with a 5 % significance level. Data were
processed using the statistical package STATA/IC 12.0.
Results
Effect of topical DermaACB application after laser
treatment
No statistical differences on clinical features between groups
were revealed before treatment (Tables 1 and 2). The clinical
evaluations (first part of outcome scale) given by three re-
searchers external from the study and the patients’ opinions
didn’t register statistical differences between groups (Table 5).
In order to reduce the average time of erythema resolution
and oedema reabsorption, after each laser session the patients
applied twice daily for 15 consecutive days the cream
Table 4 Outcome scale
Parameter Degree
Skin texture Highly improved 0; moderately improved
+1; Worsening +2.
Defect outcome Highly improved 0; moderately improved
+1; Worsening +2.
Recurrence Absent 0; light +1; moderate +2; severe +3.
Complication onset None 0; Yes +1.
Results Good 0–2; Moderate 3–5; Poor 6–8.
Erythema Absent 0; light +1; moderate +2; severe +3.
Swelling Absent 0; light +1; moderate +2; severe +3.
Good 0–2; Moderate 3–4; Poor 5–6.
 Author's personal copy
Lasers Med Sci

Table 5 Clinical outcome and patients’ opinion

Result Clinical outcome Patients’ opinion

Control n (%) DermaACB Control n (%) DermaACB

cream n (%) cream n (%)

Good 11 (55) 22 (52.4) 13 (65) 26 (61.9)

Moderate 8 (40) 17 (40.4) 6 (30) 14 (33.4)
Poor 1 (5) 3 (7.2) 1 (5) 2 (4.7)

Clinical outcome χ2 test for trend: p value = 0.944

Patient’s opinion χ2 test for trend: p value = 0.966

Fig. 2 Comparison of erythema and swelling vanishing (days) between

containing DermaACB. In order to assess the efficacy of the
experimental cream, the erythema and swelling scores were
compared with the control group results at 7, 15 and 30 days
after treatment ending. The results expressed as % patients
with erythema or swelling score 0, 1, 2 or 3 showed that the
topical application of DermaACB cream was able to signifi-
cantly reduce the inflammatory score after 15 days treatment
when compared to the standard treatment (p = 0.0016 and p =
groups. *Wilcoxon Mann–Whitney test: p value = 0.0000
0.000 for erythema and swelling respectively). No adverse
events or allergies were complained. The details of these re-
sults are summarized in Fig. 1. Overall, in terms of time res-
olution of laser-associated inflammation the obtained data
showed that the average time for the erythema resolution
was of 14.31 days (range 9 to 16 days); the average time of
swelling reabsorption was of 9.3 days (range: 7 to 15 days).
On the other hand, the control patients’ assessment showed an
average time for the erythema resolution of 24.4 days, ranging
from 13 to 24 days and the swelling was generally settled in
16.35 days, ranging from 10 to 18 days. The treatment with
cream containing DermaACB was thus able to significantly
reduce the average time of erythema and swelling resolution
when compared with the control therapy (p value = 0.0000 for
both erythema and oedema reabsorption) (Fig. 2).

Discussion

Aging is a complex process and skin aging is no exception.

Fig. 1 Graphic representation of results related to score recorded on
erythema (A) and swelling (B) vanishing in control and DermaACB-
treated groups. At 15 days the group treated with experimental cream
showed a statistically significant reduction of both erythema and swelling
score as resulted using χ2 test for trend (p value = 0.016 and p value =
0.000, respectively)
Laser rejuvenation is the most popular treatment for skin ag-
ing, fractional CO2 laser is the last introduced device that
provides efficacy and safety with a great patient’s outcome.
Skin care after laser skin resurfacing is critical for achieving a
successful result. Effective medications and management
techniques can help to minimize expected effects of the pro-
cedure such as crusting, discomfort, pruritus, erythema, and
swelling. As known, immediately after the laser, skin is dry
and desquamated and after some minute erythema and oede-
ma occur. The entity of these signs is correlated with the en-
ergy used and with the width of exposed area. More aggres-
sive and width treatment causes more acute signs and conse-
quently a longer downtime up to 45 days. Post-operative care
is commonly based on topic application of wide field antibi-
otic creams and sun screen to localize treatment while wider
treatment require more meticulous approaches.
Topic creams let an easy management but are often
insufficient to protect the treated area obligating patients
 Author's personal copy
Lasers Med Sci
to several daily application in order to reduce the risk of
hyperpigmentation or infection [18, 19]. Hyaluronic acid
sheets are generally located on the exposed area remain-
ing in situ up to the re-epithelialization is over and occlu-
sive mask is used to cover the entire face surface. These
treatments offer an optimal screen from the environment
but reduce the drainage of fluid increasing the infection
risk moreover causing social discomfort to the patient
needing to prolong the downtime [20–22].
We chose to try in our patients, after ablative laser
treatments, a new product, CERABEST™, a cream con-
taining DermaACB, a proprietary formulation containing
probiotics’ active principles. Ongoing experiments carried
in our laboratory on different cell systems (i.e. macro-
phages, fibroblasts, keratinocytes) aimed at evaluating
the mechanisms underlying the anti-inflammatory effects
of DermaACB observed in our patients, indicate that sev-
eral pathways and molecules involved in the inflammato-
ry process (cyclooxygenase II and nitric oxide synthase II
induction, pro-inflammatory cytokines and matrix-
metalloproteinase release and activation) are down-
modulated by DermaACB (manuscript in preparation).
Our results on DermaACB cream application after ab-
lative treatments showed a shorter downtime with a rapid
return to patient’s daily activities. Thus, our clinical ob-
servations, suggesting that treatment with a cream prepa-
ration containing DermaACB after ablative laser treat-
ments induces a quicker and significant reduction of
post-operative erythema and swelling, are encouraging
even if additional experimental tests will be performed
to ameliorate the treatment procedures and so further im-
prove the obtained data.
Compliance with ethical standards The Authors take under their
responsability for the manuscript. This work has never been published
or submitted publication elsewhere.
Conflict of interest The Authors declare the absences of duality of
interests and give the consent for publication.
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