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Background: Growth factors
can enhance wound repair, however, its role in post laser treatment is unclear.
The aim of this study was to establish a more advantageous method to obtain
autologous concentrated platelet plasma, which secretes growth factors, and to
evaluate its benefits in the wound healing process, including skin reactions
and adverse effects after carbon dioxide fractional resurfacing for acne scars.
Methods: A simultaneous
split face trial was conducted in 31 patients with symmetrically atrophic acne
scars on the face. Facial halves were randomly assigned to receive laser
treatment with topical autologous platelet concentrated plasma (experimental
side) or saline (control side). After
treatment, participants recorded the degree and duration of recovery and side
effects, including erythema, edema, pain, crusting, post inflammatory
hyperpigmentation and folliculitis for duration of one month.
Results: Erythema
reduction time and total duration was both faster on the experimental side,
both (p<0.05). Edema improvement time and total duration was similar, both
(p>0.05). Pain scores 12 hours post treatment were lower on the experimental
side, (p<0.05), but total duration of pain was the same. Initial time that
crusting appears and starts to peel was faster on the experimental side,
(p<0.05) and (p>0.05) respectively, but the time for the crust to peel
completely was the same. On the control side, PIH was more severe, (p<0.05),
and appearance of folliculitis was more prevalent,(p<0.05).
Conclusion: We established a
simple and economically feasible method to obtain autologous concentrated
platelet plasma, which patients evaluated could reduce erythema and pain,
enhance wound healing, and reduce adverse effects such as PIH and folliculitis
after laser treatment.
Keywords: Autologous concentrated platelet
plasma; Fractional ablative carbon dioxide laser; Acne scars; Skin reactions
after laser skin treatment; Adverse effects after laser skin treatment
INTRODUCTION
Fractional ablative carbon dioxide (CO2)
laser is a safe and currently the most effective treatment modality for acne
scars. It creates an array of microscopic treatment zones (MTZ) of thermal
injury to the skin, sparing surrounding tissues in the MTZ, allowing rapid
epidermal regeneration within 24 hours of exposure [1], which expedites wound
repair. There is evidence of a sustained long term efficacy by the detection of
heat shock protein 70 as early as two days post treatment up to 3 months post treatment, and
type III collagen in the dermal layer 7 days post treatment [2]. However, post
treatment downtime and complications are still reasons why patients hesitate to
receive such treatment. Different products and procedures to reduce these risks
are a popular research subject these days.
Platelet rich plasma (PRP)is defined as “abundant platelets that
are concentrated into a small volume of plasma [3]”,and platelets secrete fundamental
growth factors [4] that can accelerate wound healing, and is used in many areas
of medicine, including cosmetic surgery, plastic surgery, oral and
maxillofacial surgery. However, little is known about the effects of PRP
combined with laser treatment.
The traditional method of PRP extraction has
potential risks [6], and tedious procedural steps. Companies have started
selling PRP kits, and there are at least 166 types of commercially available PRP extraction
kits, but some of the products are very expensive. Using the basic principle of
PRP preparation, the aim the present study was to establish a safe, effective,
simplified, and economically feasible method to obtain autologous concentrated
platelet plasma, and to observe if it could alleviate post laser treatment skin
reaction, quicken wound healing time, and reduce adverse effects.
METHODS AND MATERIALS
Participant Selection
This study was conducted at the Peking University
People’s Hospital, Department of Dermatology. In total, thirty one participants
(23 women, 8 men; age range 21-46 years; mean age 28.6 years; Fitzpatrick skin
types III-IV) were enrolled in this study. Patients had moderate to severe
symmetrically atrophic acne scars, and had no or few inflammatory papules and
pustules on the face. Participants were excluded if they reported a history of
keloid scar formation, hypertension or diabetes, treatment with oral
isotretinoin within the preceding 6 months, immunosuppressive treatment or
disorders, pregnant or lactating women, skin dermabrasion or other forms of
skin resurfacing within the preceding 2 weeks. The study was approved by the
ethical committee of the Peking University People’s Hospital, and each
participant provided written informed consent.
Autologous Concentrated Platelet Plasma Preparation
For the preparation of autologous platelet
concentrated plasma, a slight modification of Choukroun’s PRF method [7] was used. First, 10 mL of autologous whole
blood was collected into a vacutainer collection tube with no additives and
immediately centrifuged at 3000rpm for 10 minutes. Three layers appeared: from
top to bottom are the plasma and serum, the buffy coat, and the red blood
cells. The plasma and serum is removed by a syringe into a sterile glass tube
with no additives. After the glass tube has been immobile for 5 minutes at room
temperature, a platelet clot will appear, and growth factors can be extracted after
agitation by a syringe.
Treatment Protocol
Before treatment, participants cleansed their
entire face using a mild cleanser. 60 to 90 minutes prior treatment, a topical
anesthetic cream (5% Compound lidocaine cream 5g) was applied on the face and
occluded with saran wrap, and participants were given analgesics (Ibuprofen
300mg, and Oxycodone and Acetaminophen Tablets 5mg/325mg).Each participant was
treated with ablative CO2 fractional
laser (Acupulse, Lumenis, USA). Both deep and superficial treatment modalities
were used. For the deep treatment mode, each region’s pulse energy and density
were set as follows: cheeks (15mJ/cm2, 4%), forehead (12.5mJ/cm2,
4%), and nose (17.5mJ/cm2, 4%). For the superficial treatment mode:
cheeks (60mJ/cm2, 40%), forehead 50mJ/cm2, 40%), and nose
(70mJ/cm2, 40%). After laser resurfacing, facial halves were
randomly assigned to receive topical autologous platelet concentrated plasma
(experimental group) or normal saline (control group). 1-1.5mL of plasma or
saline were applied topically and occluded for 20 minutes. Participants were
instructed not to apply any cosmetic products in the next 24 hours.
Evaluation Criteria
Participants monitored and recorded the degree and
duration of recovery and side effects, including erythema, edema, pain,
crusting, PIH and folliculitis for duration of one month. Duration and recovery
of erythema, edema, pain, and crusting was graded on a 5-point scale (0= none,
1= trace, 2= mild, 3= moderate, 4= severe). PIH graded on a 3-point scale, (0= none,
1= detectable, 2= obvious). Folliculitis was noted either as present (1) or not
(0).
Statistical Analyses
All data were analyzed using SPSS19 for Windows.
Before-and-after treatment comparisons were performed using the parametric t-test
for paired samples. Non-parametric data between the two sides were evaluated
using the Wilcoxon and McNemar test. All data p<0.05 was considered
statistically significant.
RESULTS
Subjective Evaluation
Skin Reactions
All 31 subjects completed the study.
Erythema improved on day 1.9 ± 1.2 on the experimental side, and total duration
of erythema was 7.8 ± 5.2 days. Erythema improved on day 2.6 ± 1.8 on the
control side, and total duration of erythema was 9.0 ± 5.7 days. Erythema
reduction time and total duration was both faster on the experimental side
(Figure 1), both (p<0.05).
Edema improved
on day 1.3 ± 0.7 on both sides, and lasted 2.7±1.8 days on the experimental
side, and 2.7 ± 1.9 on the control side (Figure 2), both (p>0.05).
Pain score 12
hours post treatment on the experimental side was 1.5 ± 1.1, and 1.7 ± 1.0 on
the control side. Total duration of pain was the same on both sides, lasting
1.1 ± 1.3 days. Pain scores 12 hours post treatment were lower on the experimental
side, (p<0.05), but total duration of pain was the same on both sides,
(p>0.05).
Wound Repair
Initial
crusting time on the experimental side was 1.3 ± 1.0 days, and 1.5 ± 1.1 on the
control side, initial time crusting starts to peel was 3.5 ± 2.0 days on the
experimental side, and 3.6 ± 2.1 on the control side (Figure 3), and
time it takes for the crust to peel completely on both sides was 7.5 ± 3.5
days. Initial time that crusting appears and initial time that the crust starts
to peel was faster on the experimental side, (p<0.05) and (p>0.05)
respectively, but the time it takes for the crust to peel completely was the
same, (p>0.05).
Adverse Effects
PIH was noted
in 6 patients (19.4%), out of these 6 patients, 1 patient had Fitzpatrick skin
phototype III, and 5 with phototype IV. From the experimental group, 25
patients had PIH grade of 0, 6 patients with PIH grade of 1, and 0 with PIH
grade of 2. From the control group, 25 patients had PIH grade of 0, 1 patient
with PIH grade of 1, and 5 with PIH grade of 2. The difference of PIH grade
between the two groups was statistically significant (Figure 4),
(p<0.05).
Folliculitis
post treatment was noted in 12 patients (39%). Folliculitis appeared on the
control side only in 9 patients (29%), experimental side only in 1 patient
(3%), both sides in 2 patients (6%), and neither side in 20 patients (65%). The
difference of folliculitis appearance between the two groups was statistically
significant (Figure 2 and 5), (p<0.05).
DISCUSSION
Transdermal
drug delivery is the route of administration where active ingredients are
delivered through the skin. The direct route in which drugs directly pass
through is through the stratum corneum, but at the same time it is quite thick
and difficult to permeate through, posing as the main barrier to transdermal
transport. Fractional CO2 laser creates micropores, allowing
better and faster drug absorption. In addition, as the hyperemic blood flow
increases after treatment, so does the concentration gradient between the
epidermis and the dermis, which increases permeability, resulting in better
absorption, which is further enhanced by saran wrap occlusion.
Recently,
studies on the effects of laser treatment and transdermal drugs have been
surfacing. Tan et al. [8] observed the efficacy of fractional
CO2 laser with the use of topical ointment “MEBO” on the
treatment of hypertrophic scars, results indicated the effects of combinational
use was very favorable. Higher efficacy, enhanced wound healing, shorter
downtime, and reduced adverse effects were observed. Zhu et al. [9] research on
the effects of recombinant human epidermal growth factor derivatives spray
after laser treatment showed similar results. Currently, few studies have been
completed on the combination use of laser treatment and PRP [10-14].
In recent
years, studies have proven the role of growth factors in wound repair [15].
In this study,
we took advantage of the micropores produced to increase transdermal drug
delivery and chose the timing when permeability of drugs have been increased
and topically applied and occluded for 20 minutes autologous concentrated
platelet plasma. Results indicated that autologous concentrated platelet plasma
(growth factors) combined with fractional ablative CO2 laser
treatment for atrophic acne scars can alleviate skin reactions, enhance wound
healing, and reduce adverse effects.
Autologous
Concentrated Platelet Plasma
Choukroun et al
[16] platelet rich fibrin (PRF) extraction method is very simple, and does not
require addition purchases of any special equipment. First, blood is drawn into
a glass tube without an anticoagulant, then immediately centrifuged. Three
layers will appear: red blood cell layer, PRF clot, and platelet poor plasma
(PPP) layer. The PRF clot slowly releases numerous platelets and growth
factors, and is only suitable for large open wounds or fillings.
This study used
the same principle as Choukroun’s PRF preparation to prepare autologous
concentrated platelet plasma. Besides advantages of a simplified preparation
and lack of biochemical handling, the platelet poor plasma (PPP) was not
discarded, (most methods discard the PPP). Although the platelet volume of PPP
is lower than PRP, studies have proven the amount of growth factors PDGF-αβ and
TGF-β1 in PPP is higher than whole blood [17]. In addition, PPP can increase
the proliferation of dermal fibroblasts and procollagen type 1 carboxy-terminal
peptide (PIP) [18], which is expedites wound repair.
Skin Reactions
Erythema and
edema are normal skin reactions after laser therapy. Ong et al. [19]
summarization of 13 research papers from 2003 to 2011 on fractional ablative CO2 laser
treatment indicated the average erythema duration time to be 3-14 days, and
average edema duration time was 1-3 days [20]. Our study revealed erythema
reduction time and total duration was both faster on the experiment side.
However, for edema, edema improvement and duration time in this study was very
similar between the two groups. This may be contributed by individualized edema
reactions.
Pain tolerance
differs from person to person, but
it normally subsides 1 hour post treatment
[20]. In
our study, pain scores 12 hours post treatment was less severe on the
experiment side.
Wound Repair
Crusting is an
important indication of wound repair. Results indicated initial time that
crusting appears and initial time that the crust starts to peel was faster on
the experimental side, but the time it takes for the crust to peel completely
was the same.
Adverse Effects
The incidence
rate of postinflammatory hyperpigmentation after fractional CO2
Treatment is
1-32%, with darker skin color being more prevalent [22]. In
our study, out of the 6 (19.4%) patients with PIH, the majority (83.3%) had
Fitzpatrick skin phototype IV, which is more prevalent for PIH to appear. PIH
grade was higher in the control side, and the difference between the two groups
was statistically significant.
When the skin
barrier is temporarily breached after treatment, the chances of infection
increases. Some patients are prophylactically given oral or topical antibiotics
either post or pre laser treatment [19,22], however, topical antibiotics are
not advised due to the risk of contact dermatitis [23,24]. The incidence of
folliculitis in our study was higher than other reports, this may be because no
antibiotics were prescribed, and some patients had a few inflammatory papules
or pustules when admitted. However, when compared, the incidence of
folliculitis was still lower in the experimental side, indicating that
autologous concentrated platelet plasma can reduce post treatment infection,
and does not have a risk inflicting contact dermatitis.
From this
study, we conclude that we established a simple and economically feasible
method to obtain autologous concentrated platelet plasma, which can effectively
reduce erythema and pain, enhance wound healing, and reduce adverse effects
such as PIH and folliculitis after laser treatment.
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