Journal of Plastic, Reconstructive & Aesthetic Surgery (2018) 71, 1e14

Review

Microneedling: Where do we stand now?A systematic review of the literature

Lisa Ramaut a,*, Henk Hoeksema b, Ali Pirayesh c,Filip Stillaert b, Stan Monstrey b

a University Hospital of Ghent, De Pintelaan 185, 9000 Ghent, Belgiumb Department of Plastic and Reconstructive Surgery e Burn Center, University Hospital of Ghent, DePintelaan 185, 9000 Ghent, Belgiumc Amsterdam Plastic Surgery, Jan van Goyenkade 12, 1075 HP Amsterdam, The Netherlands

Received 26 January 2017; accepted 6 June 2017

KEYWORDSMicroneedling;Percutaneouscollagen induction;Review;Scars;Skin rejuvenation

* Corresponding author.E-mail address: ramaut.lisa@gmail

http://dx.doi.org/10.1016/j.bjps.2017.01748-6815/ª 2017 British Association of P

Summary Background: Patientswho suffer from scars orwrinkles have several therapeutic op-tions to improve the appearance of their skin. The available treatment modalities that providedesirable results are often overtly invasive andentail a risk of undesirable adverse effects. Micro-needling has recently emerged as a non-ablative alternative for treating patients who are con-cerned with the aesthetic changes that result from injury, disease or ageing.Objective: This review aims to evaluate the current evidence in the literature onmicroneedling.Methods: A systematic literature review was performed by searching the electronic databasesPubMed andGoogle Scholar. The reviewed articles were analysed and compared on study design,treatment protocol, outcome parameters, efficacy measurement and results to evaluate thestrength of the current evidence.Results: Microneedling was investigated in experimental settings for its effects on atrophic acnescars, skin rejuvenation, hypertrophic scars, keloids, striae distensae, androgenetic alopecia, mel-asmaandacnevulgaris. Severalclinical trialsusedrandomisationandsingle-blindationtostrengthenthe validity of the study outcome. Microneedling showed noteworthy results when used on its ownand when combined with topical products or radiofrequency. When compared with other treat-ments, it showedsimilar resultsbutwaspreferredduetominimal sideeffectsandshorterdowntime.Conclusion: This systematic review positions microneedling as a safe and effective therapeutic op-tion for the treatment of scars andwrinkles. The current literature does show somemethodologicalshortcomings,andfurther research is requiredto trulyestablishmicroneedlingasanevidence-basedtherapeutic option for treating scars, wrinkles and other skin conditions.ª 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by ElsevierLtd. All rights reserved.

.com (L. Ramaut).

6.006lastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

2 L. Ramaut et al.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Description of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Treatment protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Efficacy measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Outcome parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Effects of interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Risk of bias individual/across studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Summary of evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Methodology of the included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Outcomes of the included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Future research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Strengths and limitations of this review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Figure 1 Rolling device.

Introduction

Although topical therapy and invasive surgery have theirspecific indications in skin treatment, methods that stim-ulate the body’s own regenerative mechanisms havecurrently gained popularity. Ablative modalities such aslasers, peelings and dermabrasion are based on partialremoval of the epidermis to trigger the growth of new skinto replace scarred or aged tissue.1 Experience has shownthat injuring the deeper layers of the skin entails a risk ofprolonged healing times, fibrosis of the papillary dermis,excessive scarring, increased photosensitivity and irregularpigmentation.2e4 These problems prompted the develop-ment of non-ablative methods that owe their efficacy totriggering dermal neocollagenesis while preserving thestratum corneum and the epidermal barrier function. Theuse of energy (e.g. non-ablative lasers, fractional lasers,and intense pulsed light) for this purpose still entails somethermal injury and necrosis,5 while the use of small needlesfor percutaneous collagen induction reaches the papillaryand reticular dermis in a purely mechanical way. Each in-dividual micro lesion is perceived by the skin as injury, butbecause the epidermal barrier is minimally disrupted,scarless wound healing will occur. This wound stage ischaracterised by the presence of transforming growth fac-tor-b3 (TGF-b3), which can be traced immunohistologicallyand highlights the activity of non-inflammatory woundhealing.6

Microneedling has by now found its way into clinicalpractice. The roller device is a drum-shaped tool with acylindrical head that is rolled back and forth to inducethousands of tiny pores in the papillary dermis (Figures 1

and 2). In addition, there is an electronic pen-shaped de-vice that has adjustable settings to control speed and depthof needle penetration (Figure 3). The unique, non-invasivepenetration of the skin that is caused by microneedling canalso serve as a way to deliver treatments like topicalproducts or radiofrequency, without causing unnecessarydamage to nearby structures. Products such as platelet richplasma (PRP) and human stem cell conditioned medium(hESC-EPC) are used to enhance the mechanism of percu-taneous collagen induction by delivering extra growth fac-tors, while others are combined with microneedling toenhance their penetration and effects [e.g. Minoxidil,depigmenting serum and tranexamic acid (TA)]. The de-livery of radiofrequency through a fractional microneedling

Figure 2 Dermal micro-injury induced by microneedling.

Figure 3 Electrical pen.

Table 1 Search results.

Google Scholar PubMed

Search term ((((microneedling)OR percutaneouscollagen induction) ORskin needling)OR dermaroller) ORdermal needling

All in title:microneedling OR‘dermal needling’ OR‘percutaneous collageninduction’ OR‘skin needling’ ORdermaroller

Results 139 156

Microneedling: A systematic review of the literature 3

radiofrequency (FMRF) device causes thermal injury fortherapeutic purposes directly to the dermis by generating acurrent between paired insulated microneedles. Thisovercomes the problem of poor penetration depth of bi-polar radiofrequency and avoids the thermal damage thatoccurs with higher levels of energy, which are necessary forpenetration.7

The trigger to form new skin can have a therapeuticbenefit when injury, disease or ageing cause aestheticchanges in the skin. The advantage of avoiding the risks ofpigmentation changes or scarring when compared to laserresurfacing and peelings makes it a valuable therapeuticalternative. Because microneedling is a simple treatmentwith a low complication rate, it was easily applied inexperimental settings, and several applications have yetbeen explored. However, no evidence-based guidelines arepresently available. This paper examines the current levelof evidence by reviewing randomised controlled trials,controlled clinical trials and prospective clinical trials thatassess the effects of microneedling on its own and com-bined with topical products or radiofrequency. All reportswere critically evaluated for methodological strengths andweaknesses, and their data were summarised to estimatethe existing evidence and to discuss which lack of evidenceneeds to be addressed in future studies.

Methods

A systematic review was performed following the PRISMAguidelines. A search for peer-reviewed published articleswas performed on the electronic databases PubMed andGoogle Scholar, followed by a screening of the bibliogra-phies of the included reports. Search terms includedMicroneedling, Percutaneous Collagen Induction, Derma-roller, Dermal Needling, Dermal Rolling, Micro Needle andSkin Needling. All terms were obtained from medicalliterature that describes microneedling and were combinedwith the Boolean operator ‘OR’ into one major search filter(Table 1). No limitations or language restrictions were set.

The last search was conducted on the 12th of August2016. The retrieved articles were assessed for eligibility byscreening study characteristics and outcome parameters.Randomised controlled trials, controlled clinical trials andclinical trials were included. Treatment protocols wereaccepted when they included microneedling alone, micro-needling with topical products as well as FMRF. Studies thatused microneedling in combination with other treatmentsthat did not specify the additional benefit of microneedlingin comparison with a control group were not included.Microneedling had to be a clearly determined variable inthe research. An exception was made for FMRF because ofits explicit technical contribution to the mechanism ofradiofrequency delivery. Studies were allowed to use activeand inactive controls. Outcome measures were screenedfor the presence of patient- and observer-based assessmentand the mentioning of adverse effects.

Methodological data were extracted from the reports ona selection of study characteristics and were summarised inTable 2. The heterogeneity was reduced by grouping thereports on indication and design. Outcome data wereextracted on clinical improvement reported by patient andobserver, and numerical and histological outcomes. Thestatistically significant differences compared to controlwere simplified to a double plus or double minus. The sta-tistically significant differences compared to baseline(outcomes in prospective clinical trials) were simplified to asingle plus or minus. Adverse effects were simplified to asymbol when a statistical analysis was carried out.

Outcome parameters based on the judgement of patientsand observers inevitably carry a subjective component.There are several well-known methodological constructionsavailable to prevent bias from affecting the validity of find-ings. All included RCTs and CCTs were screened for their useof randomisation, blinding, and full outcome reporting.Attrition bias was evaluated by screening the exclusion

Table 2 Methods.

Participants Dropouts Intervention Comparison Efficacy measurement No. oftreatments

Follow-upCat Num Histo

Acne vulgaris

CTKim et al. 25 0 FMRF baseline x x 3 12Lee et al. 20 0 FMRF baseline x x 1 8

Androgenetic alopecia

RCTDhurat et al. 100 6 MN þ minoxidil MN x x 12 12

CTDhurat et al. 4 0 MN þ minoxidil baseline x 12 72

Atrophic acne scars

RCTAlam et al. 20 5 MN negative control x 3 24Chae et al. 40 0 FMRF fractional laser

(1550 nm)x 3 20

Cachafeiro et al. 46 4 MN fractional laser(1340 nm)

x 3 24

Lehata et al. 39 1 MN þ TCA fractional laser x 6 48Lehata et al. 30 3 MN TCA-CROSS x 4 4Lehata et al. 24 4 MN þ TCA TCA-CROSS x 4 32Min et al. 23 3 FMRF bipolar RF x x x 2 8Nofal et al. 45 0 MN þ PRP TCA-CROSS

intradermal PRPx 3 2

CCTAsif et al. 50 0 MN þ PRP MN þ distilled

waterx 3 12

Chawla et al. 30 3 MN þ PRP MN þ vC x 4 1Fabroccini et al. 12 0 MN MN þ PRP x 2 32Jaishree S et al. 30 0 MN MN þ GA peel x 5 12Puri et al. 30 0 MN TCA-CROSS x 4 16

CTDogra et al. 36 6 MN baseline x 5 4El-Domyati et al. 10 0 MN baseline x x 6 2Fabroccini et al. 60 0 MN baseline x x 3 40Fabroccini et al. 32 0 MN baseline x x 2 8Imrad Majid 37 1 MN baseline x 4 8Lotfi et al. 30 0 MN baseline x x 5 8Kaftan et al. 25 0 MN baseline x 2 4

Burn scars

RCTBusch et al. 20 1 MN þ NCASCS MN, neg co x x 1 48

CTAust et al. 16 0 MN baseline x x 4 48

Hypertrophic scars and keloids

RCTFabbrocini et al. 20 0 MN þ Sili Gel MN alone,

SG alonex x 3 12

Melasma

RCTBudamakuntla et al. 60 8 MN þ TA injection TA x 3 12

CCTFabroccini et al. 20 0 MN þ depigmn

serumserum x x 2 12

Skin rejuvenation

RCTLee et al. 25 0 MN þ hESC-EPC MN x x 5 2

4 L. Ramaut et al.

Table 2 (continued )

Participants Dropouts Intervention Comparison Efficacy measurement No. oftreatments

Follow-upCat Num Histo

CTEl-Domyati et al. 10 0 MN baseline x x 6 2Fabroccini et al. 10 0 MN Baseline x xFabroccini et al. 8 0 MN Baseline x x 2 32Gold et al. 49 4 FMRF Baseline x 3 12Kim et al. 11 0 FMRF Baseline x 3 12

Striae

CCTKhater et al. 20 0 MN Fractional

laser (CO2)x x 3 24

CTPark et al. 16 0 MN baseline x x 3 12

Total 1083 49 39 12 7 139Mean 29,2702 1,5312 3,86111 17,8055

Microneedling: A systematic review of the literature 5

criteria and withdrawal. A performance bias is inevitablebecause blinding the patients and practitioners for the pro-cedure of microneedling is impossible. Reports thatmentioned randomisation without mentioning the used toolwere marked with low(*) selection bias. Reports that usedblinding but based their outcome data only on one assessorwithout numerical or histological measurement weremarked with low(*) detection bias. Reports that did notcalculate statistical significance of each treatment modalityand the difference between the compared modalities weremarked with low(*) reporting bias. Reports that lackedpatient-reported clinical outcomes weremarked with low(�)reporting bias. Attrition bias wasmarked highwhen dropoutsaffected the validity of the comparison, which is never thecase in within-patient controlled trials.

Results

Description of included studies

The search results on PubMed and Google Scholar werescreened for duplicates, which resulted in 174 unique recordsthat were screened on the basis of title and abstract. Eighty-six articles were excluded, and the remaining 88 reports werescreened on thebasis of full text. Fifty-oneof these 88articleswere excluded because they did not meet our inclusioncriteria. We excluded reviews, letters to editors, expertopinions, case reports, animal studies, in vitro studies, studiesin progress and treatment protocols that did not specificallyisolate the effects of microneedling in their comparison to acontrol group. An additional 10 records were identifiedthrough reference screening. Five of them were included inthis review based on full text. This selection process resultedin 37 included articles and is summarised in Figure 4.

Because of the heterogeneity of the included studies, ameta-analysis could not be executed.

Methods

A total of 37 reports were included in this review, of which13 randomised controlled clinical trials, 7 controlled clinical

trials and 17 prospective clinical trials. There was within-patient control in seven split-face studies and in two split-scar studies, and four of them were randomised. Of theremaining 12 controlled trials, 9 were randomised. Ten re-ports used a single-blinded evaluation setup by blinding theassessors for the used treatment. Sample sizes varied from 4to 100 with 1063 participants (393 males, 567 females and103 unknown) and a mean of 29.3. A total of 49 dropoutswere reported, with a mean of 1.53 over all reports. Micro-needling was investigated in the literature as a possibletreatment for acne vulgaris, androgenetic alopecia, atrophicacne scars, hypertrophic scars, keloid, melasma, skin reju-venation and striae distensae. The therapeutic effects ofmicroneedling were compared to those of fractional lasers(1550 Er:glass,8 1340 Erbium,9 1540 nm10 and CO2

11), tri-chloroacetic acid chemical reconstruction of skin scars (TCA-CROSS),10,12e15 bipolar radiofrequency,7 intradermal injec-tion of topical products14,16 and silicone gel.17 Methodolog-ical data are summarised in Table 2.

Treatment protocolTreatment protocol variables were needle length (mean:1.5 mm), number of treatments (mean: 3.86), treatmentinterval (mean: 4 weeks) and follow-up time (mean: 17.81weeks).

Twenty-three trials included only microneedling in theirtreatment protocol. Twelve trials compared it to baseline,one trial compared it to a negative control and 10compared it to a control group that received a differenttreatment. Nine trials combined microneedling with topicalproducts such as PRP,14,18e20 non-cultured stem cell sus-pension,21 depigmenting serum,22 Minoxidil,23,24 humanstem cell conditioned medium,25 vitamin C19 and TA.16

Six trials investigated the effects of FMRF. One trialcompared it to fractional laser,8 one to bipolar radio-frequency7 and the others to baseline.26e29 Microneedlingwas combined with TCA-CROSS in two trials, with siliconegel17 and with glycolic acid peel30 each in one trial.

Efficacy measurementThe clinical changes after a therapeutical intervention canbe assessed by the patient and an observer. All studies

Figure 4 Flowchart.

6 L. Ramaut et al.

included a subjective outcome evaluation by the assessorand objectified them with a categorical quantificationthrough the use of scales (Table 3). These provide numericdata that enable statistic weighing of the null hypothesis.The use of an objective measurement tool decreases therisk of bias entailed by subjective assessment.

Seven studies used a numerical measurement tool.Acne vulgaris was evaluated by counting the inflammatoryand non-inflammatory lesions and measuring the casualsebum level and sebum excretion rate.26,31 Lesion countand the sebum level were also used for the evaluation ofatrophic acne scars.7 The changes in skin topography ofacne scars and skin ageing were objectified with opticalprofilometry, a measuring tool that screens the surfaceirregularities of a silicon imprint from the treated site byFabbrocini et al.32e35 Lee measured skin topography with aVisiometer.25 Fabbrocini also used ultrasound to measureepidermal thickness in skin rejuvenation and keloidscars17,32 and luminance values to evaluate melasma.22

The melanin index was an outcome parameter for depig-mented hypertrophic scars and skin rejuvenation and wasmeasured using the Mexameter.21,25

Seven studies evaluated the effects of the treatmentprotocol by measuring histological changes.7,11,36e40

Epidermal thickness, collagen fibres, elastin, tropoelastinand fibroblasts were visualised with several histologicalstains. Cytokines and growth factors were visualised withimmunohistologic colouring and polymerase chain reaction(Table 4).

Outcome parametersAll 37 studies included observer-reported clinical out-comes. Twenty-eight studies included patient-reportedclinical outcomes and 29 studies reported adverse effects.

Effects of interventions

The principal summary measures were defined as differ-ence in means. Outcomes are summarised in Table 5 onpatient- and observer-reported clinical outcome, numericaloutcome, histological outcome and adverse effects.

Risk of bias individual/across studies

Twenty out of 37 included reports in this review used acontrol group and were evaluated for risk of bias. Seven outof 20 had a risk that was estimated low on all four sub-divided risks. It was high on one out of four risks in six re-ports and on two or more in seven reports. All studies havea high risk of performance bias because microneedlingcannot be replaced by placebo treatment. The risk of biasis summarised in Table 6.

Discussion

Microneedling has been the subject of several clinical trialsinvestigating its effects on atrophic acne scars, skin reju-venation, burn scars, striae distensae, androgenetic

Table 3 Categorical measurement tools.

Scale #

Acne vulgaris Global evolution acne scale 1Physician’s global assessment 1Global aesthetic improvement scale 1

Androgenetic alopecia Numbered scale (0e7) 2Atrophic acne scars Goodman and Baron 8

Echelle d’evaluation clinique des cicatrices d’acne (ECCA) 3Quantitative Global Grading System for Postacne Scarring Instrument 3Physicians global assessment (5-point scale) 1Investigators global assessment 1Numbered scale (0e5; 0e6; 0e10) 11Global aesthetic Improvement scale 1Scar severity score (3 grades) 2Quartile grading scale 7

Hypertrophic scars and keloids Visual analog scale 1Vancouver scar scale 2Patient and observer scar assessment scale (POSAS) 2

Melasma Melasma area and severity index (MASI) 2Skin rejuvenation Fitzpatrick wrinkle classification system 2

Numbered scale (0e5) 1Wrinkle severity rating scale 2Global aesthetic improvement scale 2Quartile grading 1

Table 4 Histological measurement tools.

Haematoxylin andEosin

VonGieson

Pricorius Red Masson’strichrome

Silver stain IHC PCR

Aust et al. epidermal thicknessrete ridge formation

elastincollagen

El-Domyati et al. epidermal thicknesscollagen type Icollagen type IIcollagen type VIIIelastintropoelastin

elastin new collagenformation

El-Domyati et al. epidermal thicknesscollagen type Icollagen type IIcollagen type VIIIelastintropoelastin

elastin new collagenformation

Khater et al. epidermal thicknesscollagen fibresfibroblasts

collagenfibres

Lotfi et al. epidermal thicknessrete ridge formationcollagen fibresfibroblasts

collagenfibres

elastin fibres

Min et al. collagen fibres TGFb1TGFb3IL8NFkBcollagen type Icollagen type II

GAPDHTRFb1TGFb3IL8collagen type I

Park et al. collagen fibres elastin

Microneedling: A systematic review of the literature 7

Table 5 Outcomes.

Intervention Control Patient-reportedclinicaloutcome

Observer-reportedclinicaloutcome

Numericaloutcome

Histologicaloutcome

Adverseeffects

Acne vulgaris

CTKim et al. FMRF / þ þ þ (inflam >

non-inflam)/ bleeding (5), scaling (4), cursting (6),

swelling (8), erythema (8) (all less than 1 week)Lee et al. FMRF / þ þ þ / mild pain, oedema, bleeding (procedure);

pustular eruptions (2) <1 weekAndrogenetic alopecia

RCTDhurat et al. MN þ minox minox þþ þþ þþ / none

CTDhurat et al. MN þ minox / þ þ / / none

Atrophic acne scars

RCTAlam et al. MN negative

controlþþ þþ / / minimal pain, transient erythema and oedema

Chae et al. FMRF fractionallaser

Z Z / / FRMF: none significantlaser: pain, PIHP, acne vulgaris,prolonged downtime

Cachafeiro et al. MN fractionallaser

Z Z / / both: crusts, pustules, erythema, painlaser: bullae, PIH and prolonged erythema

Leheta et al. MN þ TCA fractionallaseralternatingtreatment

Z vs laser:Z rollingtype:þþboxcar type: –icepick:Zvsalternating: –

/ / both: transient pain, oedema,erythemapeeling: desquamation

Leheta et al. MN TCA-CROSS

Z General:Z rollingtype:þþ icepicktype: –

/ / Pain: – Erythema, downtime: þþ

Leheta et al. MN þ TCA TCA-CROSS Z General:Z rollingtype: þþ

/ / Z

8L.

Ramautetal.

Min et al. FMRF bipolar RF satisfaction:þþpain: –convenience: –

þþ þþ(inflam <

non-inflam)

þþ Pain: – FMRF: transient erythema, oedema

Nofal et al. MN þ PRP TCA-CROSSintradermalPRP

Z Z / / MN: erythema and oedema, pain TCA: PIH,mild painPRP: pain, mild bruises (one patient)

CCTAsif et al. MN þ PRP MN þ

distilledwater

þþ þþ / / acne, PIH, milia, persistent erythema, bruising

Chawla et al. MN þ PRP MN þ vC þþ þþ / / /Fabroccini et al. MN þ PRP MN / þþ / / transient erythema and oedemaSharad et al. MN þ GA peel MN / þþ / / transient erythema, PIHPuri et al. MN TCA-

CROSSe Z / / MN: transient erythema, pain; oedema TCA: PIH

CTDogra et al. MN / þ þ / / postinflammatory hyperpigmentation, tram

track, small ecchymosisEl-Domyati et al. MN / þ þ / Z (1 month)þ

(3 months)facial oedema, slight pain, mild erythema

Fabroccini et al. MN / / þ þ / erythema, bruising over bony prominenceFabroccini et al. MN / / þ þ / /Imran Majid MN / þ þ / / temporary erythema, postinflammatory

hyperpigmentation (one patient), mild crustingLotfi et al. MN / þ þ / / transient erythema, mild to severe pain during

procedureKaftan et al. MN / / þ / / /

Burn scars

RCTBusch et al. MN þ

NCASCSMN,neg co

Z Z þþ / /

CTAust et al. MN / þ þ / þ swelling and bruising

Hypertrophic scars and keloids

RCTFabbrocini et al. MN þ

SGSG / þþ Z / /

Melasma

RCTBudamakuntla et al. MN þ TA injection TA / Z / / itching, burning, erythema

CCT(continued on next page)

Micro

needlin

g:Asyste

matic

revie

wofthelite

rature

9

Table 5 (continued )

Intervention Control Patient-reportedclinicaloutcome

Observer-reportedclinicaloutcome

Numericaloutcome

Histologicaloutcome

Adverseeffects

Fabroccini et al. MN þdepigmentingserum

depigmentingserum

/ þþ þþ / transient erythema and oedema

Skin rejuvenation

RCTLee et al. MN þ

hESC-EPCMN Z þþ þþ / mild desquamation (one patient)

mild pain, transient erythemaCTEl-Domyati et al. MN / þ þ / þ slight pain, erythema, oedemaFabroccini et al. MN / / þ þ / mild oedema, erythema and swelling

(48e72 h)Fabroccini et al. MN / / þ þ /Gold et al. FMRF / / þ / / mild-moderate erythema and oedema, painKim et al. FMRF / unclear þ / / minimal pain, bruising (1 week) crusts

Striae

CCTKhater et al. MN fractional laser þþ þþ / þþ MN: transient mild erythema

laser: PIHCTPark et al. MN / þ þ / þ pain, erythema, spotty bleeding, pruritus

Legend: þþ: statistically significantly different in advantage of microneedling; þ: statistically significantly better in prospective clinical trial; Z: no statistically significant differencebetween the therapy regiments; -: statistically significantly worse in prospective clinical trial; –: statistical significantly different in disadvantage of microneedling; /: no data;FMRF Z fractional microneedling radiofrequency; MN Z microneedling; TCA Z trichloroacetic acid; PRP Z platelet rich plasma; vC Z vitamin C; GA Z glycolic acid; SG Z silicone gel;NCASCS Z non cultured stem cell suspension; h-ESC EPC Z human embryonic stem cells-endothelial precursor cells; PIH Z post-inflammatory hyperpigmentation; CSL Z casual sebumlevel; SER Z sebum excretion rate.

10L.

Ramautetal.

Microneedling: A systematic review of the literature 11

alopecia, melasma and acne vulgaris. It has been comparedto other treatments such as fractional lasers, topicalproducts and peelings.

To strengthen the validity of the research, some trialsused control groups, randomisation and single blinding.Measurement was made through scoring the assessors’ andpatients’ findings on scales, numeric measurement toolsand histological evaluation on skin biopsy. Microneedlingtriggers regenerative mechanisms and activates non-inflammatory wound healing in the treated skin. It acti-vates the release of cytokines and molecules thatcommunicate to induce skin cell proliferation and differ-entiation, neoangiogenesis and collagen formation.

Table 6 Risk of bias.

Selection bias Detection bias

Randomisation Blinding assessorAndrogenetic alopecia

RCTDhurat et al. low low

Atrophic acne scars

RCTAlam et al. low lowChae et al. low (*) lowCachafeiro et al. low lowLeheta et al. low low (*)Leheta et al. low (*) low (*)Leheta et al. low low (*)Min et al. low (*) lowNofal et al. low (*) low

CCTAsif et al. high unclearChawla et al. high highFabroccini et al. high unclearJaishree S et al. high highPuri et al. high high

Burn scars

RCTBusch et al. low high

Hypertrophic scars and keloids

RCTFabbrocini et al. low (*) high

Melasma

RCTBudamakuntla et al. low high

CCTFabroccini et al. high high

Skin rejuvenation

RCTLee et al. low low

Striae

CCTKhater et al. high high

(*) no randomisation tool mentioned(*) subjective outco

Biopsies of the treated sites showed an epidermal thick-ening and increased collagen deposition in a normal wovenpattern.

The investigated literature lacked the methodologicalunity to be included in a meta-analysis. However,microneedling has shown to be a safe and effectivetherapeutic modality for the treatment of atrophic scars,ageing and skin disorders and proved to be useful for theadmission of topical products and radiofrequency. Itsucceeded to deliver results that could complement and,in some cases, replace the more invasive therapeuticregimens while showing less side effects and shorterdowntime.

Attrition bias Reporting bias

Exclusion, withdrawal All outcomes reported

high low (*)

low low (*)low lowhigh lowlow highlow lowlow lowlow lowlow low

low low (*)low highlow low (�)low low (�)low high

low high

low low (�)

high low

low low (�)

low low (*)

low low (*)

(*): statistics incomplete(�): no patient reported outcome

me data by one assessor

12 L. Ramaut et al.

Summary of evidence

The use of needles for non-ablative skin treatment was firstdescribed by Orentreich and Orentreich in 1995 as subcisionsurgery, which is the release of depressed scars and wrinkleswith a needle from their attachment to the underlying skin.This controlled trauma leads to the formation of connectivetissue to fill the created gap.41 A few years later, in 1997,Camirand and Doucet introduced tattooing without pigmentas Needle Dermabrasion and proposed it as a technique toimprove the appearance of achromic, hypertrophic and un-sightly scars.42 However, this device never gained widepopularity due to the tight grouping of the needles, whichmade it prone to over-treating and scarring. In 1996, skinneedling using a roller device was introduced by Fernandesat the International Society of Aesthetic Plastic Surgery(ISAPS) congress in Taipei.43 Fernandez designed his pilotroller device as a drum-shaped tool with a cylinder with3 mm needles that reach the fibroblasts deep in the reticularlayer. However, this needle length proved to be way toopainful to use in an office setting, and it caused unaccept-able bleeding and bruising for the patient. Zeitter et al.confirmed the observation that Fernandes made in 2008 that1 mm needles show similar results to 3 mm needles, with theextra advantage of less downtime, swelling and pain3,44

Methodology of the included studies

The validity of the study results is determined by themethodological setup. Thirteen of the 37 included studysetups used randomization, 10 included single-blindationand two performed a power analysis for sample size9,45 toimprove methodological quality.

There was a noticeable difference in treatment regi-mens. Patients were treated between 1 and 12 times withtreatment intervals varying from 1 to 8 weeks. There is nostandard treatment protocol available, but Zeitter et al.(2014) performed a study on rats to investigate the effectsof repetitive treatments. They observed the best resultswhen the treatment was repeated four times with an in-terval time of 3 weeks.44 The choice of needle length de-pends on the pursued depth of therapeutical intervention(e.g. thick scar tissue) and requires generalised anaesthesiafor needles longer than 2 mm.

A second striking difference was observed in the time tofollow up, which varied between 1 and 72 weeks. Studiesthat performed interim follow-up evaluations observed thatthe effects of microneedling changed over several monthsto reach a maximum at 12e24 weeks. Fabroccini et al. evenreported the most significant results at 8e12 months posttreatment.34 This means that the 25 studies that hadfollow-up times shorter than 24 weeks might have under-estimated the effects of microneedling.

Scales were used to objectify clinical outcomes reportedby patients and observers. The heterogeneity in the usedscales made it impossible to combine different study samplesin a meta-analysis. The Goodman and Baron scale for theevaluation of atrophic acne scars was the most universallyused evaluation scale.46 Second was the use of a numberedscale, like the Visual Analog Scale, but unfortunately therewere differences in thenumbers given to themaximumscore.

Histological measurement was based on the knowledgegained from animal studies about the histological changesthat appear after microneedling. The increase in epidermalthickness, increased collagen and elastin deposition andthe presence of non-inflammatory cytokines and growthfactures like TGF-b3 are measurable to demonstrate effi-cacy.2,44,47 Researchers may be reluctant for the labourintensity of a histological evaluation, but the importance ofhistological outcome parameters is highlighted from thescarceness of objective measurements of changes in skinquality.

Fifty percent of the studies that used a control group didnot report a complete statistical analysis. Outcome datafrom two study groups should be weighed statistically toidentify a significant difference compared to baseline andbetween groups. Only three studies calculated the signifi-cance between groups, three other studies calculated onlythe comparison of each group to baseline and Puri et al.(2015) did not perform either analysis.15 The remainingthree were incomplete because there was no statisticalanalysis performed on any of their outcome parameters.These shortcomings were accounted for in the estimation ofthe reporting bias (Table 6, marked with (*)).

Outcomes of the included studies

In the current literature,microneedlingwas investigated in avariety of settings. First, it gained evidence for its use onatrophic acne scars. Compared to lasers and peels, micro-needling caused comparable clinical results to these main-stream therapies but with an explicit advantage because ofits lower risk of side effects. Hypertrophic scars are lessinvestigated, and a hypertrophic tendency in the patient isoften an exclusion criterion in trials that use microneedling.The rationale behind this is that triggering skin formationdoes not fit in a state of hypertrophic tendency. The fewexisting trials that did include hypertrophic scars did notethe advantages of microneedling especially when combinedwith topical products that aid repigmentation.

Second, microneedling enhances penetration of topicalproducts. It appeared to increase the effectiveness oftopically applied minoxidil on androgenetic alopecia anddepigmenting serum on melasma. Other topical productsenhanced the percutaneous collagen induction by providingextra growth factors such as PRP for atrophic acne scarsand h-ESC-EPC for skin rejuvenation. Badran et al. (2009)investigated the penetration of topically applied radio-labelled mannitol into full thickness human skin graftsspontaneously and combined with microneedling. Hydro-phylic compounds like mannitol are expected to have apoor penetration by passive diffusion through the stratumcorneum. The authors also noticed differences in penetra-tion between two drug carrier fluids (invasomes or buffersolution), which implicates that the nature of the topicalproducts plays a role in the effectiveness of the combina-tion therapy.48

The delivery of radiofrequency through insulated pairedmicroneedles proved to improve the aesthetic appearanceof atrophic acne scars, ageing skin and acne vulgaris andshowed to be superior compared to the effects of bipolarradiofrequency.7 It demonstrates beneficial effects on in-flammatory lesions, which contradicts the commonly used

Microneedling: A systematic review of the literature 13

exclusion criterion for microneedling, i.e. the presence ofactive skin infection and inflammation. This criterion ex-cludes patients with active acne, which is often still presentin patients with atrophic acne scars. Some studies opted fortopical or oral antibiotic prophylaxis,30,45,49 but none of thereports included in this review mentioned bacterial in-fections after microneedling. In-vitro studies have shownthat there is a transdermal passage of microorganismsthrough the micropores after microneedling, but there is noincreased risk of infection when microneedling is performedwith standard hygienic measurements like a sterile deviceand skin disinfection. It even showed less contaminationcompared to intradermal needling.50

Frequently reported adverse effects are transient ery-thema, oedema and pain. Very rare cases of post-inflammatory hyperpigmentation,18,49 a side effect that iscommonly reported after the use of lasers and peelings, areassumed to have appeared after not following instructionsto protect the treated skin from sunlight for a few days.The appearance of the ‘tram track scarring’ was describedby Dogra et al., and in one case report, the authorsconcluded that the scarring occurred due to high pressureon the needling and the use of long needles over bonyprominences.51 A second case report described allergicreaction and systemic hypersensitivity after microneedlingin three patients. These problems were caused by the useof a topical product that was not suitable for deep admin-istration and the use of a product that had earlier causedhypersensitivity in the patient.52 These events illustratethat even though microneedling is a simple and non-invasive therapeutical option, there is a need for clearand evidence-based guidelines to avoid these undesiredside effects or complications.

Future research

Future research should aim for a strengthening of the cur-rent evidence by conducting more qualitative randomisedcontrolled clinical trials with standardised measurementtools and lengthy follow-up times. In addition, the effectsof microneedling on hypertrophic scars and keloids have notbeen examined properly and thus need further research.This could truly establish the evidence that would posemicroneedling as a valuable evidence-based treatmentoption for treating scars, wrinkles and other skinconditions.

Strengths and limitations of this review

The strength of this review lies in the fact that it provides acomplete overview of the current use of microneedling.The shortcomings of the current literature involvingmicroneedling were highlighted to serve as a guideline forfuture research.

The main limitation of this study is the inability toperform a meta-analysis due to the heterogeneity of theincluded studies. The main objective of this review was togive an overview of the current literature, which includesthe mentioning of less qualitative studies. These interferedwith the possibility to cluster the qualitative study out-comes into a general conclusion.

Conflict of interest

None.

Funding

None.

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