Microneedling for Transepidermal
Drug Delivery on Stretch Marks
Gabriela Casabona and Paula Barreto Marchese
Abstract
Stretch marks (SMs) are a well-recognized,
common skin condition that rarely cause any
significant medical problems but are often a
significant source of distress to those affected.
The origins of SM are poorly understood, and a
number of treatment modalities (Elsaie et al.
2009) are available for their treatment, yet
none of them is consistently effective, and no
single therapy is considered to be consensus
for this problem. Multiple sittings of treatments
such as chemical peelings, micro-
dermabrasion, nonablative and ablative laser
techniques, and light and radiofrequency
devices are performed to improve the SM
appearance. Microneedling and transepidermal
drug delivery together are a new modality of
treatment for SM. It is based on stimulation of
collagen production and enhancement of the
penetration of certain active substances across
the skin with which it is possible to achieve
satisfactory results.
Keywords
Microneedling • Transdermal drug delivery •
Transepidermal drug delivery • Stretch marks •
Collagen
G. Casabona (*) • P.B. Marchese
Clinica Vida – Cosmetic, Laser and Mohs Surgery Center,
São Paulo, Brazil
e-mail: grcasabona@uol.com.br;
paulabarreto_@hotmail.com
# Springer International Publishing AG 2018
M.C.A. Issa, B. Tamura (eds.), Lasers, Lights and Other Technologies, Clinical Approaches and Procedures in
Cosmetic Dermatology 3, https://doi.org/10.1007/978-3-319-16799-2_38
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488
Stretch Marks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488
Microneedling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
The Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
Mechanisms of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
Microneedling and SM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492
Microneedling and Transepidermal Drug
Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492
Vitamin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493
Ascorbic Acid (Vitamin C) . . . . . . . . . . . . . . . . . . . . . . . . . . 493
Platelet-Rich Plasma (PRP) . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Uses and Doses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Other Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
Contraindications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
Advantages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
Disadvantages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
Side Effects and Their Management . . . . . . . . . . . . . . 496
Microneedling and Vitamin C Drug Delivery
Plus Calcium Hydroxylapatite Fillers: A Pilot
retrospective Study for Stretch Marks . . . . . . . . . . . 496
Authors’ Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 498
Take Home Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 500
487
488
Introduction
Stretch marks (SMs) are an undesirable cutaneous
disorder, which causes significant cosmetic prob-
lems with an evident psychological impact. There
is loss of the normal random collagen distribution to
the level of the mid-dermis or deeper (Singh and
Kumar 2005). A single treatment modality that is
consistently effective with minimal adverse effects
does not exist to date. There are several modalities
of treatment such as topical tretinoin 0.1% cream,
topical 20% glycolic acid, microdermabrasion,
lasers, and light and radiofrequency devices. Micro-
needling therapy is a new addition to the treatment
techniques for SM. It is a simple, inexpensive office
procedure, with small downtime that allows colla-
gen stimulation and transepidermal drug delivery
(TDD). Percutaneous collagen induction goal is to
stimulate collagen production by using the chemical
cascade that happens after any trauma. Approxi-
mately 5 days after the skin injury, a fibronectin
matrix forms with an alignment of the fibroblasts
that determines the deposition of collagen
(Widgeron 2012). Treatment with skin needling
should be able to promote the removal of old dam-
aged collagen and induce more collagen growth
beneath the epidermis. The microneedling devices
have micron-sized needles that can perforate the
skin in a minimally invasive and low pain level
manner (Kaushik et al. 2001), thereby creating aque-
ous transport pathways within the skin referred to as
microchannels. Many active substances can be
delivered into the skin by microneedling. In this
chapter, we will focus on the delivery of three com-
ponents, which are effective on treating stretch
marks. They are vitamin A, vitamin C, and
platelet-rich plasma (PRP). The development of
microneedling associated with drug delivery seems
to be a good option in SM treatment. Combined,
they are able to effectively change the collagen
organization, transforming the SM skin into a
more healthy skin.
Stretch Marks
Stretch marks (SMs) are an undesirable cutaneous
disorder, which causes significant cosmetic prob-
lems with an evident psychological impact. It
G. Casabona and P.B. Marchese
occurs mainly in adolescence, pregnancy, and
obesity (Satish 2009).
Causes of SM are not clear, and a number of
theories were proposed. Infection leading to the
release of striatoxin that damages the tissues in a
microbial toxic way, mechanical effect of
stretching, which is proposed to lead to rupture
of the connective tissue framework (e.g., preg-
nancy, obesity, weight lifting), normal growth as
seen in adolescence and the pubertal spurt that
leads to increase in sizes of particular body
regions, increase in the levels of adrenocorticotro-
pic hormone and cortisol which are thought to
promote fibroblast activity leading to increased
protein catabolism and thus alterations to collagen
and elastin fibers (Cushing’s syndrome, local or
systemic steroid therapy), genetic factors (absence
of striae in pregnancy in people with Ehlers-
Danlos syndrome and their presence as one of
the minor diagnostic criteria for Marfan syndrome
suggest an important genetic element).
SM can be divided into striae rubrae (Fig. 1a)
and striae albae (Fig. 1b). They are distinct, evo-
lutionary linked forms of SM and their distinction
has therapeutic implications. The color of the SM
is related to the stage of evolution and to melano-
cyte mechanobiological influences.
Striae rubra is an erythematous striae; as it
matures, it becomes white and more atrophic in
the end; it is an atrophic dermal scar with overly-
ing epidermal atrophy. Initially, striae appear as
flattened areas of thinned skin with a pink-red hue
that may be pruritic. They usually increase in
length and width and acquire a darker reddish-
purple appearance over time. The typical white,
depressed appearance of older striae develops
with time along the long axis aligned parallel
with the normal lines of skin tension.
Histologically, striae display an atrophic, thinned
epidermis with a flattening of the rete pegs. There is
loss of the normal random collagen distribution to
the level of the mid-dermis or deeper. Elastin stains
reveal scarce or absent elastin fibers and reduced
fibrillin in the papillary and reticular dermis within
affected areas; the elastin fibers present appear tan-
gled and frayed. The pathogenesis and those pre-
disposed to developing SM may have an underlying
deficiency of fibrillin 54. This histologic appearance
Microneedling for Transepidermal Drug Delivery on Stretch Marks
Fig. 1 (a) Striae rubrae,
(b) striae albae
probably likely results from mast cell degranulation
and macrophage activation (McDaniel 2002) with
resultant destruction of both collagen and elastin
fibers (Budamakuntla 2013).
A universal approach to evaluating the severity
of SM and a treatment modality that is consis-
tently effective with minimal adverse effects do
not exist to date.
There are several modalities of treatment:
(a) Topical treatments
– Tretinoin 0.1% cream is thought to work
through its affinity for fibroblasts and
induction of collagen synthesis (Bernard
2002). It has maximal efficacy in striae
rubrae and poor, unpredictable responses
in striae albae. It seems to decrease in mean
length and width of the SM after months of
daily use. Studies have demonstrated that
improvement in the clinical appearance of
striae after treatment with retinoic acid cor-
relates with new fibrillin production
(Fisher 1995).
– Creams and lotions that contain actives such
as Centella asiatica extract, vitamin E,
vitamin A, collagen-elastin hydrolysates,
panthenol, and menthol are widely used,
mainly by women during pregnancy. Scien-
tific data available are not sufficient to con-
clude that such creams are effective, and
larger studies are needed to determine the
efficacy and safety of such products. There
is no statistically significant evidence to
support their use in the prevention of SM.
– Topical 20% glycolic acid (GA) pure or
mixed with other substances such as
0.05% tretinoin or 10% L-ascorbic acid
489
improves the appearance of striae alba,
but the precise mechanism of action of
GA is still unknown. It is reported that
GA stimulates collagen production by
fibroblasts and increase their proliferation,
but further investigations and studies are
required to prove such theory.
(b) Lasers and light devices: intense pulsed light
(515–1.200 nm), 585 nm flashlamp-pumped
pulsed dye laser (PDL), 308 nm xenon chloride
(excimer laser), 577 nm copper bromide laser,
1.450 nm diode laser, 1.064 nm Nd:YAG laser,
carbon dioxide (CO2) laser, fractionated 1550
nm erbium-doped fiber laser and fractional
photothermolysis are some examples of tech-
nologies that can be used in SM treatment
(Alster and Handrick 2000, 2005). Prior to
selecting one device, one must perform the
correct analysis of the SM and of the patients’
Fitzpatrick skin type to diminish the risk of
injuries and pigmentary alterations.
(c) Radiofrequency (RF) devices: the effects of
dermal heating are well recognized and
include immediate effects on collagen struc-
ture with stimulation of dermal fibroblasts
inducing a synthesis of new collagen fibers
(neocollagenesis) and elastic fibers (neo-
elastogenesis) (Al-Himdani et al. 2014; Gold
2015), improving the appearance and histo-
logical findings in SM (Suh et al. 2007).
(d) Microdermabrasion is a skin resurfacing tech-
nique using aluminum oxide. It has been
reported to increase type I collagen and has a
greater effect on stretch marks. This technique
can be used in combination with intradermal
platelet-rich plasma (PRP); in a study, patients
were treated with a combination of intradermal
490
®
Fig. 2 Dermaroller device
PRP and microdermabrasion in the same ses-
sion. There was significant clinical improve-
ment of SM in patients treated with a
combination of PRP and microdermabrasion
when compared with patients treated with just
microdermabrasion. A combination of PRP and
microdermabrasion in the same session showed
better results in short duration (Ibrahim et al.
2015).
(e) Microneedling therapy is a new addition to the
treatment techniques for SM. It is a simple,
inexpensive office procedure, with small down-
time that allows collagen stimulation and trans-
epidermal drug delivery (TDD). Substances
such as vitamin A (retinyl palmitate and retinyl
acetate), vitamin C, and platelet-rich plasma
(PRP) can be used for TDD. In this chapter, we
are going to describe the use of the microneed-
ling technique as a way of stimulating collagen
and facilitating the delivery of active ingredients
to the skin affected by stretch marks.
Microneedling
History
In 1995 Orentreich described collagen percutaneous
stimulation with dermal needling for scars. Then, in
1997, Camirand and Doucet described needle
G. Casabona and P.B. Marchese
®
Fig. 3 Dermapen device
dermabrasion using a “tattoo pistol” to treat scars.
And only in 2006 a doctor from South Africa, Dr
Desmond Fernandes, developed percutaneous col-
lagen induction therapy with the dermaroller
(Dermaroller®) (Henry et al. 1998) (Fig. 2). In
2010 a new electronic pen-shaped device
®
(Dermapen ) (Fig. 3) was developed in Australia
for a more cost-effective procedure. Using the pen
you can choose different needle lengths and speed
vibration providing not only microneedling but also
a certain level of dermabrasion depending in the
used technique.
Since then, the use of the microneedling
devices is growing along with the number of
indications. The addition of transepidermal drug
delivery to the microneedling technique made it
even more interesting to treat certain conditions,
such as stretch marks and melasma.
The Devices
Since 2006, when the first dermaroller was used
by Dr Fernandes, the device suffered numerous
changes to get more ergonomic and resistant.
The standard dermaroller used for acne scars is
a drum-shaped roller studded with 192 fine
microneedles in 8 rows, 0.5–1.5 mm in length
and 0.1 mm in diameter. The microneedles are
synthesized by reactive ion etching techniques
on silicon or medical-grade stainless steel. The
Microneedling for Transepidermal Drug Delivery on Stretch Marks 491

Phase I Phase II Phase III

Inflammatory Proliferation Remodeling

Proliferation:
Growth Factors Monocytes/ Fibroblats/ Conversion
TGF-b1/3 Keratinocytes collagen III-!
PDGF Fibronectin matrix Tissue remodeling
Extracellular matrix COLLAGEN DEPOSITION Vascular
proteins ( type III) maturation

Fig. 4 Cascade of healing after trauma injury and collagen deposition

instrument is sterilized by gamma irradiation.
Now you can find thinner versions and larger
versions, and the length of the needles can come
up to 2.5 mm.
As it is supposed to be disposable, if you have
more than one needle length indication, the doc-
tor would have to use more than one roller, which
is not cost-effective to the patient. For example,
if you want to treat the patient under the eyes
and for a scar in the malar area, we would
have to use both 1.0 mm- and 1.5–2.0 mm-long
needles.
Other electronic pen-shaped microneedle
devices were developed with disposable needles.
The length and the speed vibration of the exposed
needle, in and out, can be controlled. In the end,
with these devices, we can not only create micro-
tunnels but also achieve a certain level of derm-
abrasion of the epidermis, if that is the goal.
Mechanisms of Action
The microneedle devices create microtunnels that
vary from 0.5 to 2.5 mm in depth (Cho 2010).
Percutaneous collagen induction goal is to stimu-
late collagen production by using the chemical
cascade that happens after any trauma. There are
three phases in the body’s wound healing process
(Tejero-Trujeque 2001), which follow each other
in a predictable fashion. This has been well
described in The Biology of the Skin by Falabella
and Falanga (Falabella et al. 2000). Platelets and
eventually neutrophils release growth factors such
as the connective tissue growth factor, TGF-B1,
TGF-B3, platelet-derived growth factor, connec-
tive tissue activating protein III, and others that
work together to increase the production of
intercellular matrix (Lynch 1989; Tran 2004;
Faler 2006) (Fig. 4). Only then, monocytes also
produce growth factors to increase the production
of collagen III, elastin, glycosaminoglycans, and
so on (Johnstone 2005).
Approximately 5 days after the skin injury, a
fibronectin matrix forms with an alignment of the
fibroblasts that determines the deposition of col-
lagen. Eventually, collagen III is converted into
collagen I, which remains for 5–7 years. Due to
this conversion, the collagen tightens naturally
over a few months (Martin 2005).
Normally, during the usual conditions of
wound healing, scar tissue is formed with minimal
regeneration of normal tissue (Fenske 1986). Per-
cutaneous collagen induction causes even further
tightening of lax skin and smoothening of scars
and wrinkles several weeks or even months after
the injury (Fernandes 2002). In addition, percuta-
neous collagen induction has proven to be very
effective in minimizing acne and burn scars, by
promoting the replacement of scar collagen with
normal collagen and the reduction of depressed
and contracted scars (Ruszczak 2003).
492
Treatment with skin needling should be able to
promote the removal of old damaged collagen and
induce more collagen growth beneath the epider-
mis. Puncturing the skin multiple times in acne
scars increases the amount of collagen and elastin
deposition. Thus, it was hypothesized that skin
needling would also be useful in SM because
these seem to be dermal scars with epidermal
atrophy (Majid 2009).
Microneedling and SM
A study made in South Korea in 2012 enrolled
16 volunteers with SM, who received three treat-
ments with a microneedling device at 4-week
intervals. Clinical response to treatment was
assessed by comparing pre- and posttreatment
clinical photographs, skin biopsies, and patient
satisfaction scores. The general histopathologic
features of the lesional specimens collected before
treatment showed epidermal thinning with fine
dermal collagen bundles arranged in straight
lines. After treatment, the epidermis was thick-
ened, and the amounts of dermal collagen and
elastic fibers were increased (McCrudden et al.
2015). This study proved that microneedling can
be effectively and safely used for SM treatment.
In addition to this technique, the trans-
epidermal drug delivery can be associated in
order to increase the collagen production.
Microneedling and Transepidermal
Drug Delivery
The dispersion and effectiveness of active ingre-
dients into the skin, without prior perforation, are
severely limited by the inability of the large
majority of drugs to cross the skin at therapeutic
rates due to the great barrier imposed by the skin’s
outer stratum corneum layer (Menon et al. 2012).
In 2004, Prausnitz (Prausnitz 2004), described
the use of microneedles for transdermal drug
delivery. The outstanding motivation for micro-
needles is that they can provide a minimally inva-
sive means to transport molecules into the skin
(Oh et al. 2015).
G. Casabona and P.B. Marchese
As with lasers, the microneedling technique
started being used as a way to trespass the stratum
corneum to deliver active ingredients to the skin in
a more efficient way (Brauer et al. 2014).
The stratum corneum (SC), the skin’s outer-
most layer, is a barrier that prevents molecular
transport across the skin. Therapeutic agents,
such as peptides, proteins, and oligonucleotides,
are difficult to reach deeper layers of the skin by
conventional methods or topical delivery
(Petchsangsai et al. 2014).
The microneedling technique (MT), as shown,
uses micron-sized needles that can perforate the
skin in a minimally invasive and low pain level
manner, thereby creating aqueous transport path-
ways within the skin referred to as microchannels
(Park et al. 2012).
Moreover, these microchannels present no lim-
itation regarding the size of molecules that can
pass through their tunnels (Kumar and Banga
2012). While, in terms of size, the microchannels
are in the range of microns, the macromolecules
delivered are typically nanometers in size.
The only question that remains is if, after the
microneedling, blood and fibrin will invade the
microchannels creating a new barrier for this pen-
etration (Milewski et al. 2010). Consequently, we
recommend, as the biopsies presented in Fig. 5, to
proceed in an inverse technique, where the drug is
applied prior to the microneedling technique and
prior to each step to guarantee more efficient
delivery of the active ingredient.
In the past, local microinjections, the so-called
mesotherapy, were introduced in France by Pistor
(Pistor 1979). Mesotherapy is a widely used tech-
nique in medicine. This technique consists of
intradermal or subcutaneous microinjections of
0.05–0.1 mL of highly diluted drug mixtures or
a single drug, on body parts affected with medical
or aesthetic problems. Nevertheless, recent stud-
ies show that the drug delivery with micro-
needling is more effective than mesotherapy
because it not only allows the penetration of active
ingredients into the skin but also induces the
chemical cascade that takes place after a trauma
which will stimulate collagen production.
Many active substances can be delivered into
the skin by microneedling. Depending on the
Microneedling for Transepidermal Drug Delivery on Stretch Marks
Fig. 5 Histopathology of the skin after methylene blue ink
diluted in the same vitamin C vehicle used to do the drug
delivery. Applied prior every dermroller pass, 20 passes
disease you wish to treat, there are a number of
substances that can be chosen, for example, ste-
roids (triamcinolone acetonide) for hypertrophic
scars and areata alopecia, tranexamic acid for
melasma, minoxidil for androgenetic alopecia,
and aminolevulinic acid for actinic keratosis.
In this chapter, we will focus on the delivery of
three components, which are effective on treating
stretch marks. They are vitamin A, vitamin C, and
platelet-rich plasma (PRP).
Vitamin A
The possibility of using vitamins A and C for
percutaneous collagen induction has been
described by Aust in (2008). Vitamin A, a retinoic
acid, is an essential vitamin also considered a
hormone for the skin. It expresses its influence
on many genes that control proliferation and dif-
ferentiation of all the major cells in the epidermis
and dermis (Rosdahl 1997). Percutaneous colla-
gen induction and vitamin A switch on the fibro-
blasts to produce collagen and therefore increase
the need for vitamin C. Vitamin A may control the
release of TGF-B3 in preference to TGF-B1 and
TGF-B2 because, in general, retinoic acid seems
to favor the development of a regenerative lattice-
patterned collagen network rather than the parallel
deposition of scar collagen found with cicatriza-
tion (Oliveira Marcela et al. 2016).
493
(a) After 0,5 dermaroller, (b) after 1 mm dermaroller. Both
showed penetration of the ink in different levels according
to the needle length
Retinyl palmitate (RP) is an ester of retinol and
is the major form of vitamin A found in the epi-
dermis. It has a high molecular weight and a stable
formulation. To be active, RP has to be enzymat-
ically converted in the skin to retinol by cleavage
of the ester linkage and then be converted to
tretinoin via oxidative processes. It has been
established that the topical administration of RP
for 14 days in rats resulted in increased protein
and collagen and an epidermal thickening (Ro et
al. 2015).
Ascorbic Acid (Vitamin C)
Ascorbic acid (AA) or vitamin C is also essential
for the production of normal collagen. Percutane-
ous collagen induction and vitamin A stimulate
the fibroblasts to produce collagen and therefore
increase the need for vitamin C. Topical vitamins
A and C both maximize initial release of growth
factors and stimulate collagen production (Palma
2006).
Apart from its role as a potent antioxidant, it has
also been demonstrated that AA functions as an
essential cofactor for the enzymes lysyl hydroxy-
lase and prolyl hydroxylase, both of which are
required for the posttranslational processing of
types I and III collagen (Nusgens 2001).
AA stimulates collagen production in the der-
mis and can cause a dramatic increase in fibroblast
494
proliferation potentially resulting in greater colla-
gen production; it might be presumed that AA
also possesses the potential to increase collagen
production for SM appearance reduction. AA
even plays a role in collagen synthesis at the
level of gene expression. It has been shown to
upregulate collagen synthesis and increase the
synthesis of the inhibitor of metalloproteinase-1
which decreases UV-induced collagen
degradation.
Platelet-Rich Plasma (PRP)
PRP is a source of numerous growth factors which
facilitate repair and healing. It is a potential reser-
voir of essential growth factors, including
platelet-derived growth factor, vascular endothe-
lial growth factor, transforming growth factor-
beta 1, and insulin-like growth factor which play
an important role on the recovery of the skin
(Sonker et al. 2015).
It has been found to accelerate endothelial,
epithelial, and epidermal regeneration, stimulate
angiogenesis, enhance collagen synthesis, pro-
mote soft tissue healing, decrease dermal scarring,
enhance the hemostatic response to injury, and
reverse the inhibition of wound healing caused
by glucocorticoids.
There are different preparation protocols to
obtain PRP, and physicians should select proper
PRP preparations after considering their biomo-
lecular characteristics and patient indications.
A split-face comparative study published in
2014 of microneedling with PRP versus micro-
needling with vitamin C in treating atrophic post-
acne scars revealed better results with micro-
needling and PRP. Thirty patients with post-acne
atrophic facial scars were offered four sittings of
microneedling with PRP on one side and micro-
needling with vitamin C on the other side of the
face at an interval of 1 month. Overall results were
better with microneedling and PRP (Chawla
2014).
PRP along with microneedling would intensify
the natural wound healing cascade because of the
high concentration of patients own growth factors.
It acts synergistically with growth factors induced
G. Casabona and P.B. Marchese
by skin needling in order to enhance the wound
healing response. As stretch marks are atrophic
scars, we can hypothesize that microneedling and
PRP would have good results for them.
Uses and Doses
It is very important to assure that the substances
that are going to be applied on the skin surface
prior microneedling are substances that could be
used intradermally or intravenously.
For stretch marks’ treatment, we indicate the
use of:
– Fifteen to 20% vitamin C (L-ascorbic acid
0,15 g/ml or L-ascorbic acid 0,2 g/ml) ampoules.
– Retinyl palmitate (an ester of retinol) ampoules
for endovenous administration can be safely
applied topically.
– MTS ® ampoules: a combination of palmitoyl
tripeptide-28 3% and growth factors 10%.
– PRP preparations (follow proper protocols).
Procedure
During treatment, the needles pierce the stratum
corneum and create microconduits (holes) without
damaging the epidermis. It has been shown that
rolling with a dermaroller (192 needles, 200 mm
length and 70 mm diameter) over an area for
15 times will result in approximately 250 holes/cm2.
Microneedling is a mild pain drug delivery.
Because the skin’s stratum corneum barrier has
no nerves, skin anatomy provides the opportunity
to pierce needles across the stratum corneum with-
out stimulating nerves. Although, the microneedles
are inserted only deep enough to reach the superfi-
cial dermis, which is not much painful, probably
because their small size reduces the odds of
encountering a nerve or of stimulating it to produce
a strong painful sensation (Figs. 6a, b and 7a, b).
1. Take photographs of the area you are going to
treat using a consistent background, position,
and lighting, and they will be compared with
the posttreatment images.
Microneedling for Transepidermal Drug Delivery on Stretch Marks 495

Fig. 6 (a) 1 day before treatment; (b) 30 days after one session of microneedling with TDD of vitamin C and non-cross-
linked hyaluronic acid

®
Fig. 7 Before (a) and after 30 days (b): one session Dermapen TDD with sterile vitamin C + AH non-cross-linked

2. Anesthetize using a thick application of topical
anesthetic cream for about 60 min. Remove it
completely before starting the procedure to
prevent topical anesthetic intoxication.
3. Clean the area with alcoholic chlorhexidine.
4. Choose a device: roller or pen.
5. Choose depth of the needle and speed of the
pen (quicker vibrations lead to less abrasion).
6. Choose the active ingredient to use (the use of
sterile and injectable products is important to
avoid the risk of infection and also diminish
the risk of contact dermatitis).
7. Apply a thin layer of the liquid with a dispos-
able brush.
8. Pass the device and repeat the process over and
over. Roll at least 20 passes in the same area in
different ways, and pen pass at least ten times in
each area making circular movements.
9. Clean just the excess of liquid and blood (leave
a thin layer of blood for at least 4 h to function
as a natural PRP dress that helps to heal).
10. Cover the skin with a sterile active ingredient
in an oleous vehicle such as glycosaminogly-
®
cans (Antiage Flash Mesoestetic) to prevent
water loss through the skin.
11. Cover with a thin plastic drape.
12. Instruct the patient to follow strict photo-
protective measures. Schedule sittings are at
intervals of 4 weeks.
Other Indications
• Androgenetic alopecia, areata alopecia, acne
scars, hypertrophic scars, melasma, skin regen-
eration, and preparation of skin prior to fat
graft
496
Contraindications
• History of contact dermatitis especially to
metal and to the active ingredients that are
going to be used
• Chronic Urticaria
• Immunosuppression
• Diabetes
• Pustular or nodular rosacea or acne
• Anticoagulant medications
• Pregnancy
• Moles (always verify moles prior to treat the
area and try to avoid using microneedling on
top of them)
• Keloids
• Skin infection
• Psoriasis (Koebner phenomenon)
Advantages
– Nonablative.
– Healing process is fast (1–5 days depending on
needle length and number of passes) and has
less chance for complications if compared to
ablative techniques.
– The immediate effects are a thicker and more
resistant skin.
– Can be used in every skin type even off face.
– Low cost if compared to lasers.
Disadvantages
– Training required.
– If a very high density or coverage is used, then
the healing time and erythema can last longer.
– Does not promote immediate tightening of the
collagen fibers.
– Requires more than one session to achieve
good results.
Side Effects and Their Management
The microneedling treatment is well tolerated.
Minor side effects reported are mild pain at the
treating area, erythema, spotty bleeding, and
G. Casabona and P.B. Marchese
pruritus for 2 or 3 days after the procedure,
which are solved without any specific treatment.
Moisturizing creams can be applied to keep the
area hydrated, which diminishes the discomfort.
Infection at the treating area is very unlikely to
happen. As the microholes close almost immedi-
ately, postoperative infections are rare. If they
occur, oral or topic antibiotics can be used for
treatment.
Irritant or allergic contact dermatitis can occur
depending on the characteristics of the substance
applied on the skin surface and the immunological
characteristics of the patient. Oral antihistamines
and topical steroids can be used if necessary
(Soltani-Arabshahi et al. 2014).
Hyperpigmentation is uncommon, but if it hap-
pens, topical Kligman formula can be applied. For
long-lasting erythema, micropulsed YAG laser,
pulsed dye laser (PDL), and intense pulsed light
(IPL) devices can be used. The emergence of
papules and pustules on the treating area must be
treated with topical or oral antibiotics used in acne
and rosacea treatment.
A case report study published in 2014 reports
three patients who developed facial allergic gran-
ulomatous reaction and systemic hypersensitivity
after microneedling drug delivery therapy. Micro-
needles are powerful means of transdermal deliv-
ery of drugs. Thus, only chemicals approved for
intradermal injection are safe to be used in con-
junction with microneedling. Application of vari-
ous nonapproved topical products before a
microneedling procedure can introduce immuno-
genic particles into the dermis and potentiate local
or systemic hypersensitivity reactions (Lima et al.
2013). For facial allergic granulomatous reaction
and systemic hypersensitivity, oral steroids and
minocycline can be used, but the treatment is not
always effective.
Microneedling and Vitamin C Drug
Delivery Plus Calcium Hydroxylapatite
Fillers: A Pilot retrospective Study
for Stretch Marks
Calcium hydroxyapatite (CH) is a white substance
made of microspheres (45 mm) of CH in a
Microneedling for Transepidermal Drug Delivery on Stretch Marks 497

carboxymethyl cellulose gel and is a filler and Table 1 Drugs and vitamins with scientific evidence to be
biostimulator because it is supposed to induce used prior to microneedling and its effects
neocollagenesis during the first 6 months after Substance Effect
injection. CH can be used either in the subcutane- Vitamin A Growth factor release, regulates
ous layers to volumize a region or in the dermis to differentiation and proliferation of the
epidermis and dermis, skin
correct dermal atrophy. It is made to be applied in regeneration, increased protein and
more deep planes such as subcutaneously, and collagen, epidermal thickening
when it is injected more superficially, it can give Vitamin C Stimulates collagen production in the
a yellowish look. The CH injection into SM in all dermis, increases fibroblast
depths intends to improve atrophy (Casabona proliferation resulting in greater
collagen production
e Michalany 2014) through the stimulation of
Platelet-rich Enhances collagen synthesis
the production of endogenous collagen and also plasma
to promote a yellowish look to the striae promot-
ing a more natural appearance matching the color
of the normal skin (Berlin et al. 2008; Parvicic
2015).
Table 2 Side effects: how to manage
Side effect Management
Infection Oral or topical
antibiotica
Authors’ Experience Contact dermatitis Oral antihistamine and
topical can be steroids
A Retrospective study conducted at private Hyperpigmentation Topical Kligman
office in São Paulo, Brazil (publishing process), formula
during a 3-year period (January 2012 to July Long-lasting erythema Micropulsed YAG laser,
2015), enrolled 35 patients with stretch marks pdl or ipl
Acne and rosacea Oral antibiotica and
in different regions of the body (gluteus, thighs,
topical acne treatment
knees, abdomen, and breasts) and evaluated the
Facial allergic Oral steroids,
efficacy of a new combined treatment for SM; granulomatous reaction and minocycline
the dermal injection of calcium hydroxyapatite systemic hypersensitivity
and microneedling with vitamin C drug delivery a
Lymecycline, minocycline, tetracycline)
were put together to enhance the appearance
of SM.
Among 35 patients, there was one male
(2.85%) and 34 females (97.14%). Twenty five first session included the dermal injection of cal-
(71.42%) had red SM and ten (28.57%) had cium hydroxyapatite (Radiesse ®) followed by
white SM. Ages ranged between 21 and microneedling (Dermapen ®) and topical applica-
34 years, and they were submitted to the same tion of 20% vitamin C onto the affected areas. The
treatment for SM (Table 1). three remaining sessions included microneedling
Patients had their SM evaluated by a physician with vitamin C drug delivery, with no dermal
observer and scores were assigned in accordance injections.
to a visual analogue scale, the Manchester Scar All the 35 patients had better scores according
Scale (Table 2). This evaluation was performed at to the Manchester Scar Scale evaluation at the end
the beginning and after the end of treatment ses- of the study. Thirty patients were asked about their
sions. Both scores were compared in order to level of satisfaction with the treatment: 8 patients
identify if there was an improvement in the (27%) were very satisfied, 15 patients (50%) were
appearance of stretch marks. satisfied, 5 patients (7%) were neither satisfied nor
Patients were submitted to four treatment ses- dissatisfied, 2 patients (6%) were unsatisfied, and
sions with a 4-week interval between them. The none answered very unsatisfied.
498
®
Fig. 8 Before (a) and after (b) two sessions of Dermapen TDD with sterile vitamin C. In this case one session of CaHa
injection was also done before TDD
®
Fig. 9 Before (a) and after (b) two sessions of Dermapen TDD with sterile vitamin C. In this case one session of CaHa
injection was also done before TDD
Results are encouraging. With the injection
calcium hydroxyapatite and microneedling with
vitamin C topical application, it is possible to
stimulate collagen production in three different
pathways at the same time. This combined tech-
nique may have better results than those obtained
when each technique is performed alone (Figs. 8a,
b, 9a, b, 10a–f, and 11a–d).
Conclusions
The improvement in the appearance of SM, rather
than its complete removal, is a more realistic
clinical goal. Complete disappearance of SM
G. Casabona and P.B. Marchese
may be occasionally observed; nevertheless, this
occurrence is uncommon and should not be pre-
sented to patients as a realistic goal.
Using combination of treatments over a pro-
longed period of time can improve the appearance
of striae. Unless a revolutionary monotherapy
becomes available that dramatically improves
striae treatment results, the use of multimodal
treatments tends to increase (Goldberg et al.
2005) consistently.
The development of microneedling associ-
ated with drug delivery seems to be a good
option in SM treatment. Combined, they are
able to effectively change the collagen organi-
zation, transforming the SM skin into a more
healthy skin.
Microneedling for Transepidermal Drug Delivery on Stretch Marks 499

®
Fig. 10 Before and after two sessions of Dermapen before (a) and after (b). Gluteus left side before (c) and
R
TDD with sterile vitamin C. In this case two sessions of after (d); gluteus right side before (e) and after (f)
CaHa injection were also done before TDD. Inner thigh

• Microneedling and transepidermal drug delivery

Take Home Messages
together are an option of treatment, with which it
is possible to achieve satisfactory results.
• Stretch marks are often a significant source of
• Skin needling promotes the removal of old
distress to those affected, and no single therapy
damaged collagen, induces more collagen
is considered to be a consensus for this problem.
500 G. Casabona and P.B. Marchese

Fig. 11 Before and after

®
two sessions of Dermapen
TDD with sterile vitamin
C. In this case one session
of CaHa injection was also
done before TDD. Right
thigh before (a) and after
(b), left thigh before (c) and
after (d)

growth beneath the epidermis, and creates
aqueous transport pathways within the skin
for drug delivery.
• Vitamin A, vitamin C, and platelet-rich plasma
are substances that can be used for drug delivery.
• Microneedling with drug delivery is a cost-
effective office procedure, well tolerated, and
with few minor side effects and short down-
time that can be safely used for SM treatment.
• The injection of calcium hydroxyapatite into
SM prior the microneedling with vitamin C
topical application is an innovative combined
technique that may have even better results.
• The improvement in the appearance of SM,
rather than its complete removal, is a more
realistic goal.
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