PHARMACOTHERAPEUTICS

Pharmacologic and Other Noninvasive

Treatments of the Aging Face: A Review of the
Current Evidence
Samyd S. Bustos, MD1
Summary: Aging of the face is the result of the interrelation of three-
Krishna Vyas, MD, PhD, MHS1 dimensional changes occurring over time among the 5 different layers of the face
Tony C. T. Huang, MBBS, MS1 and its associated structures. Knowledge regarding the causes of these changes
Marissa Suchyta, MD, PhD1 and identification of new key anatomic structures have helped elucidate one
Nathan LeBrasseur, MS, PhD2 of the most complex areas of the human body. This has resulted in the intro-
Sebastian Cotofana, MD, PhD3 duction of pharmacologic agents to help stop, mitigate, or counteract signs of
Saranya P. Wyles, MD, PhD4,5 aging and restore the youthful appearance of the face. The authors performed
Samir Mardini, MD1 a systematic search of the literature to review the current highest-level evidence
Rochester, MN of facial antiaging pharmacologic agents. Pharmacologic and minimally invasive
antiaging treatments can target different components of facial aging and con-
tinue to evolve. With continuous research efforts, traditional treatments, such as
botulinum toxin type A, injectable fillers, and chemical peels, are emerging in
newer, more effective formulations, with longer lasting clinical results. However,
for soft-tissue descent and facial volume loss, surgery remains the standard treat-
ment. An adequate understanding of the three-dimensional process of facial
aging over time (the fourth dimension), facial anatomy, and the pharmacologic
properties of antiaging/rejuvenation agents are the sine qua non of facial anti-
aging treatment. The specific modality should be tailored to patient characteris-
tics, preferences, and goals. (Plast. Reconstr. Surg. 154: 829e, 2024.)

F
acial aging is part of the natural human decreased tissue elasticity, craniofacial remodel-
“aging mosaic.”1 It reflects the cumulative, ing including loss of bony skeleton support, and
dynamic, and interdependent structural adipose tissue redistribution (Fig. 1).3
changes of the skin, soft tissues (ie, subcutaneous Intrinsic skin changes may include thinning
fat, muscle, fascia, ligamentous structures), and of the epidermis, flattening of the dermal–epider-
structural support (bone and teeth) of the face, mal junction, decreased cell turnover, atrophic
leading to changes in facial volume and topogra- dermis and fewer fibroblasts, loss of subdermal
phy.2 Aging is associated with a general descent of adipose tissue, and decreased collagen. Extrinsic
the soft tissues and has been generally described skin changes are the result of exogenous insults,
as an inverted triangle. This contrasts with the such as photodamage, smoking, weight changes,
“triangle of youth,” defined by high cheekbones, and poor nutrition, resulting in dry skin, rhytids,
full cheeks, and a well-defined jawline. The fac- and dyspigmentation.4 Histologically, the dermis
tors contributing to facial aging are multifactorial, atrophies and elastic fibers become more irregu-
including genetics, gravity, photoaging, medical lar.5 Soft-tissue changes include deflation, descent,
comorbidities, diet, chronic smoking or alcohol and deterioration, with fat accumulation in the
use, weight changes, stress, environmental factors, lower face.6 The underlying bony framework also

From the 1Division of Plastic and Reconstructive Surgery, Disclosure statements are at the end of this article,
2
Robert and Arlene Kogod Center on Aging, 3Department
following the correspondence information.
of Clinical Anatomy, 4Department of Dermatology, and
5
Center for Regenerative Medicine, Mayo Clinic.
Received for publication August 6, 2022; accepted May 18,
2023. Related digital media are available in the full-text
Copyright © 2023 by the American Society of Plastic Surgeons version of the article on www.PRSJournal.com.
DOI: 10.1097/PRS.0000000000010767

www.PRSJournal.com 829e
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 Plastic and Reconstructive Surgery • October 2024

Fig. 1. Skin and soft-tissue changes of the aging face. SMAS, superficial musculoaponeurotic sys-
tem. Used with permission of Mayo Foundation for Medical Education and Research. All rights
reserved.

changes: the infraorbital rim and anterior maxilla appearance of the human face. An adequate under-
gradually retrude, contributing in part to devel- standing of facial anatomy, facial changes with
opment of the tear-trough deformity; the orbit time, and mechanisms of antiaging or rejuvena-
expands; the overall facial height decreases; and tion agents are fundamentals of facial antiaging
facial structures rotate downward and inward treatment. Procedural rejuvenation techniques
with respect to the cranial base, further changing range from skin rejuvenation (eg, chemical peels
the overall facial appearance.7 The visible signs and lasers) to volumizing procedures with fillers
of aging can include features such as deep and to surgical procedures (eg, fat grafting, implants,
hollow horizontal and vertical rhytides, temporal and rhytidectomy). In this review, we present the
atrophy, volume loss in the midface, deep naso- current evidence of facial antiaging pharmaco-
labial folds, and jowls. Therefore, rejuvenation logic agents and noninvasive treatments.
often seeks to address ptosis and atrophy of tissues
and reverse the inverted cone of youth.
Enhanced understanding of facial aging has METHODS
resulted in improvements of technique and intro- A literature review was performed with the
duction of technologies to restore the youthful assistance of an academic medical librarian with

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 Volume 154, Number 4 • Noninvasive Treatments of the Aging Face

key terms related to face aging and pharmaco- Mechanism of Action

logic agents, including, but not limited to, fillers, BoNTA acts at the neuromuscular junc-
neurotoxins, lasers, biostimulators, and chemical tion to cause muscle paralysis by inhibiting the
peels. The search was performed on April 18, 2022, release of acetylcholine from presynaptic motor
with multiple databases, including Ovid EBM neurons. The polypeptide chain has a heavy
Reviews–Cochrane Central Register of Controlled and a light chain linked by a disulfide bond.
Trials, Ovid Embase (1974–), Ovid Medline The heavy chain binds irreversibly at high
(1946–, including publish online ahead of print, affinity to receptors at the presynaptic surface
in-process, and other nonindexed citations), and of cholinergic neurons. The light chain inter-
Scopus (1970–). Results were limited to English- acts with different proteins, such as SNAP25
language meta-analyses, systematic reviews, and (synaptosomal-associated protein, 25 kDa),
select randomized controlled trials (RCTs). All VAMP (vesicle-associated membrane protein),
results were exported to EndNote (Clarivate), and syntaxin, in the nerve terminals, and pre-
where obvious duplicates were removed. Search vents fusion of acetylcholine vesicles with the
strategies are provided in the Appendix. (See cell membrane.8 Onset and peak effect vary by
Appendix, Supplemental Digital Content 1, which formulation but typically occur within 3 to 7
demonstrates the search strategy for the scientific days after injection. Due to irreversible receptor
literature review, http://links.lww.com/PRS/H40.) blockage, function is recovered by nerve sprout-
ing and formation of new synapses, which takes
Neurotoxins approximately 3 months.
Indications Profile
Botulinum toxin type A (BoNTA) is a neu- Each approved BoNTA product has distinct
rotoxin produced by Clostridium botulinum. pharmacologic and clinical properties, result-
BoNTA provides temporary improvement in the ing in unique attributes. Each product differs in
appearance of moderate to severe glabellar lines molecular size and structure, protein contents,
associated with corrugator or procerus muscle physiochemical properties, biologic activity,
activity and moderate to severe lateral canthal potency, immunogenicity, manufacturing pro-
lines associated with orbicularis oculi activity cess, dose requirements, duration, and adverse
(Table 1). BoNTA formulation varies by brand. event (AE) profile. Units of measurement for the
Several are approved by the U.S. Food and Drug 3 commercially available BoNTA preparations
Administration (FDA) for nonaesthetic uses (eg, are proprietary to each manufacturer and are
Myobloc), whereas others (eg, Botox, Dysport, not interchangeable.10 Product-related factors,
Xeomin, Jeuveau) are FDA-approved for use to such as onset, duration, potency, diffusion, and
treat mimetic rhytides. These products are often migration, have implications on efficacy and pre-
used off-label for the treatment of bunny lines, dictability. Patients should be assessed in terms of
gummy smile, masseter reduction, or platysmal aesthetic goals with consideration of functional
bands.8 Some providers modify dosage from man- anatomic animation.
ufacturer guidelines to achieve desired effects.
For example, reconstituting BoNTA with less vol- Outcomes
ume increases concentration to reduce injection Patient satisfaction with BoNTA treatments
site spread and avoid unwanted effects, such as remains high (see Table, Supplemental Digital
brow ptosis. Content 2, which presents systematic reviews
with meta-analyses of RCTs of botulinum toxin
Contraindications injections for treatment of the aging face, http://
Contraindications include active infection links.lww.com/PRS/H41),11–18 including reduced
(eg, active acne), allergy to neurotoxin or its depression scores with glabellar injection. In a
constituents (eg, cow’s milk allergy for Dysport), 2019 systematic review of patient-reported out-
or known neuromuscular disorders.8 Different comes for cosmetic indications of BoNTA, treat-
excipients, such as the stabilizing agent human ment generally resulted in improved satisfaction
serum albumin, must be considered. Some new and quality of life metrics, such as perception of
formulations use polysorbate 20 instead, but it youthfulness, attractiveness, affect, mood, and
can also cause allergies.9 Relative contraindica- self-confidence.19 Compared with placebo, abo-
tions include pregnancy, breastfeeding, keloid botulinumtoxinA (ABO; 50 U), onabotulinum-
formation, immunocompromised state, or body toxinA (ONA; 20 U), and incobotulinumtoxinA
dysmorphic disorder. (INCO) had higher success rates when assessed

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 Plastic and Reconstructive Surgery • October 2024

Table 1. Botulinum Toxin Injections

Recom-
mended
Target Dose Management of
Area Muscles (Units) Important Considerations Adverse Events Adverse Events
Vertical Corrugator 15–30 Avoid injecting too inferior, Upper eyelid ptosis from 0.5% Apracloni-
forehead/ supercilii, avoid the orbital rim diffusion affecting LPS dine eye drops
glabellar procerus,
complex depressor
supercilii
Horizontal Frontalis 15–25 1–2 cm above supraorbital rim Upper eyelid ptosis, eye- 0.5% Apracloni-
forehead to avoid ptosis brow asymmetry dine eye drops
Lateral orbital Orbicularis 10–15 Maintain 1 cm lateral to bony Ecchymosis, upper lid Ice pack and hold-
rhytids oculi per orbit to avoid diffusion into droop with asymmetric ing pressure
(crow’s feet) side orbit; avoid injecting below smile due to involve- to minimize
and smile arch (may result in zygomati- ment of ZM bruising
lines cus major paralysis)
Bunny lines Nasalis, pro- 2–5 Superficial injections; avoid Flattening of the cheek, Conservative, reas-
cerus levator labii superioris nasolabial fold, or upper surance
alaeque nasi and levator labii lip droop from involve-
superioris ment of levator labii
alaeque nasi and levator
labii superioris muscles
Perioral Orbicularis 4–6 Inject within 5 mm of vermil- Drooling, speech prob- Conservative, reas-
rhytids oris ion; avoid midline or corners lems, or asymmetric surance
of the lips (may case flatten- smile
ing or drooling)
Dimpled chin Mentalis, 5–10 Avoid injecting too superior to Lower lip inversion, Weakening of
cobble ston- avoid depressor labii speech problems, eating the orbicularis
ing problems oris on the side
sitting lower:
inject 0.5–1 U
intradermally
Marionette Depressor 5–10 Superficial injections; 1 cm Lower lip inversion, Weakening of
lines anguli oris inferior and lateral to oral speech problems, eating the orbicularis
commissure problems oris on the side
sitting lower:
inject 0.5–1 U
intradermally
Platysmal Platysma 15–25 BoNTA will not correct skin Dysphagia or dysphonia Consider soft diet
bands per laxity for first days,
band small bites
Nasal flares Lower nasalis 1–2 per BoNTA into the columella can Lip asymmetry Conservative,
side help reduce downturn of the reassurance
nose while smiling; BoNTA
into the outer nostrils can
help reduce nasal flare when
smiling
LPS, levator palpebrae superioris; ZM, zygomaticus major.

by participants (relative risk, 21.2, 19.5, and 66.5, related to unwanted spread or diffusion of the
respectively) and physicians (relative risk, 14.9, toxin into adjacent and distal muscles, resulting
17.1, and 134.6, respectively) at week 4. ABO-50U in brow or eyelid ptosis.20 Other potential compli-
did not differ from ONA-20U in success rates at cations include ecchymosis, local site pain or skin
week 4. Major AEs were more likely in the ABO- reactions, infection, headaches, hypersensitivity,
50U group compared with the ONA-20U group or facial neuromuscular symptoms. BoNTA is also
(odds ratio, 2.6), with no difference in AE rates known to carry a risk of strabismus or eyelid sen-
overall. INCO-24U did not differ from ONA- sory disorders. A 2022 systematic review and meta-
24U in physician-assessed success rate at week 4. analysis evaluated the incidence of AEs related to
Ptosis was the primary major AE reported. cosmetic glabellar and forehead BoNTA injections
in 4268 patients receiving BoNTA and 1234 partici-
AEs and Complications pants receiving placebo and found an overall com-
Most complications of BoNTA injections plication rate of 16%.12 This percentage was also
are mild, transient, and low in severity. They are reflected in a study from the United Kingdom.21

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 Volume 154, Number 4 • Noninvasive Treatments of the Aging Face

Table 2. Dermal Fillers

Type and Name Composition Duration of Effect (mo) Reversal Agent
Collagen
 Zyderm Bovine collagen 2–4 None
 Cymetra Cadaveric collagen 3–6
 Cosmoplast Cell-cultured collagen 3–4
Hyaluronic acid
 Belotero Balance Cohesive polydensified matrix HA ≈12 Hyaluronidase
 Juvéderm Crosslinked HA 3–6
 Perlane HA with particle size 940 and 1090 μm 6–12
 Restylane HA with particle size 250 and 500 μm 6–12
Synthetic fillers
 ArteFill 20% Polymethylmethacrylate suspended in 80% solution ≈50% permanent None
with 3.5% bovine collagen and 0.3% lidocaine
 Radiesse 30% Calcium hydroxylapatite microspheres/70% carrier gel 12–24
 Sculptra 367.5 mg powder of poly-L-lactic acid microspheres 12–24

A 2021 Cochrane Review14 assessed the safety preperiosteal plane rather than the deeper fat or
and efficacy of BoNTA in the treatment of facial muscle layers. Facial fillers are generally divided
rhytides in adults. RCTs with more than 50 partici- into 2 main groups: traditional dermal fillers
pants comparing BoNTA with placebo, other types (mainly based on hyaluronic acid [HA]) and bio-
of BoNTA, or fillers were included in the analysis. stimulators (Figs. 2 and 3). There is only 1 FDA-
A total of 65 RCTs involving 14,919 randomized approved dermal filler that is nonabsorbable; it is
participants were included, but the overall risk composed of polymethylmethacrylate beads sus-
of bias was unclear. Based on studies of 1 treat- pended in a solution containing bovine collagen.
ment cycle of the glabella, AEs were low. However, This filler is approved for the treatment of naso-
the authors stated that there is a lack of evidence labial folds and cheek acne scars. Biostimulators
about the effects of multiple cycles of BoNTA, fre- aim to restore the volume and appearance of the
quency of major AEs, duration of effect, and effi- skin, but also work by stimulating the body’s natu-
cacy, particularly for recently approved BoNTA ral production of collagen and elastin to reduce
formulations.14 the appearance of fine rhytides. These are typi-
Formation of neutralizing antibodies after cally injected into the jowls, cheeks, and temples.
BoNTA injections may be responsible for treat- Calcium hydroxylapatite (CaHa) and poly-L-lactic
ment failure in nonresponders. Rahman et al.13 acid are fillers that fall into the category of bio-
published a meta-analysis in 2022 to quantify the stimulators. Although these biostimulators are
prevalence of neutralizing antibodies after treat- FDA-approved only for noncosmetic indications,
ment with ONA, ABO, or INCO across multiple their off-label use has become a mainstay of facial
therapeutic indications in 8833 patients. The antiaging treatment.
incidence of neutralizing antibodies in aesthetic
indications was rare (summary estimate, 0.002) Contraindications
compared with therapeutic indications (with Major contraindications are active infection
higher, longstanding doses), such as for dystonia near the site of infection; known hypersensitivity
(7.4%) or spasticity (6.7%). to the filler or to components, such as lidocaine;
and glabellar necrosis with injected collagen
Fillers products. Autoimmune disease or immunosup-
pression are not contraindications. CaHa should
Indications not be used around eyes or lips and may result
Facial fillers (Table 2) are injectable treat- in nodule formation. This product is radiopaque
ments that aim to restore volume loss and obscure and can be seen on radiographs and computed
the appearance of mimetic rhytides. The ideal tomography scans.
filler should be long-lasting, safe, biocompatible,
inert, reversible, and easy to use; should age with Mechanism of Action
the patient; and should have predictable prop- HA is a linear mucopolysaccharide that is a
erties and aesthetic results. Most FDA-approved major component of connective, epithelial, and
dermal fillers are temporary. They are injected neural tissues. HA is a glycosaminoglycan that is
into the deep dermis, subcutaneous tissue, or part of the extracellular matrix, and produces

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 Plastic and Reconstructive Surgery • October 2024

Fig. 2. Common injection techniques of dermal fillers. Used with permission of Mayo
Foundation for Medical Education and Research. All rights reserved.

a viscoelastic network for collagen and elastin in the FDA premarket approval database search
fibers to bind together. Sources for dermal fillers link (https://www.accessdata.fda.gov/scripts/
can be from bacteria or rooster combs (avian). cdrh/cfdocs/cfPMA/pma.cfm).23
Some include lidocaine to decrease discomfort
Outcomes
with injection. CaHa is a biostimulator filler that
Dermal filler injections can significantly
contains uniform CaHa microspheres suspended
increase soft-tissue volume. (See Table,
in an aqueous carboxymethylcellulose gel car-
Supplemental Digital Content 3, which presents
rier.22 Poly-L-lactic acid is a polymer composed
systematic reviews with meta-analyses of RCTs of
of lyophilized crystals resuspended in water.
dermal fillers for treatment of the aging face,
Polymethylmethacrylate is a biodegradable, bio-
http://links.lww.com/PRS/H42.)24–29 It has also
compatible polymer composed of microspheres
been shown that both medial (forehead, medial
(20%) suspended in a bovine collagen gel.
midface, and perioral labiomandibular sulcus)
Profile and lateral face (temple, lateral midface, and jaw-
A summary of safety and effectiveness data in line) injections can create local lifting effects up
addition to health care provider and patient label- to 1 mm.30 Lateral face injections, in particular,
ing for each approved dermal filler can be found can create additional regional lifting effects by

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 Volume 154, Number 4 • Noninvasive Treatments of the Aging Face

Fig. 3. Common injection sites of dermal fillers. Used with permission of Mayo Foundation for
Medical Education and Research. All rights reserved.

influencing neighboring facial regions.30 A pro- for nasolabial fold treatment found that both
spective, observational registry study of 158 partici- were equally safe and well tolerated, with statis-
pants to assess safety and effectiveness of HA-based tically significant improvements on the Wrinkle
fillers demonstrated that 93.9% of treatments Severity Rating Scale and the Global Aesthetic
provide improvement at 3 months after injection, Improvement Scale with polycaprolactone com-
with minimal common treatment reactions and pared with HA.33 A 2020 randomized, double-
no clinically significant AEs.31 Notably, more than blinded, split-face trial showed suitable efficacy
76% of treatments still offered visible effect at 12 and safety of the novel polycaprolactone-based
months. Highly concentrated crosslinked HA fill- dermal filler compared with polynucleotide fillers
ers may last for more than 12 months.32 for correction of crow’s feet.34
Results of biostimulator injections can last up
to 2 years. Many patients will have booster treat- AEs and Complications
ments of 1 vial every 12 months. More recently, On May 28, 2015, the FDA issued a safety
new biostimulator dermal fillers, including poly- communication about serious reported complica-
caprolactone and polynucleotide fillers, have tions with inadvertent injection into blood vessels
been studied. A 2015 randomized, blinded, split- in the face, which could include vision distur-
face trial comparing polycaprolactone with HA bances, blindness, stroke, and damage to skin and

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 Plastic and Reconstructive Surgery • October 2024

underlying structures.35 A 2021 meta-analysis27 to achieve a desired effect. Fully ablative lasers
assessing AEs of HA injections for lip augmenta- [ALs], or traditional lasers, create a confluently
tion demonstrated that the 5 most common AEs ablated tissue extending to the superficial dermis.
were tenderness (88.7%) and injection site swell- ALs also cause a deep layer of denatured colla-
ing (74.3%), mass (27.3%), contusion (48.7%), gen below ablated areas.38 Nonablative fractional
and pain (19.7%). Occurrence of herpes labialis lasers (fractional picosecond lasers, fractional
(0.6%) and granulomatous foreign body reaction nonablative lasers, and fractional ALs) work by
(0.6%) were identified in fewer cases. The most distributing laser energy into the dermis through
feared complications (filler-associated necrosis pixelated columns or through an array of lenses
and life-threatening angioedema) were reported creating microthermal zones or microscopic epi-
in fewer than 0.3% of cases. The site at most risk dermal necrotic debris.40 Fractional picosecond
of necrotic complications is the glabellar region, lasers produce multifocal vacuoles in the epider-
due to the lack of strong collateral circulation.36 mis, which is largely unaffected between vacuoles.
Prevention of intraarterial injection may be Fractional nonablative lasers produce multifocal
achieved with precise knowledge of vascular anat- epidermal and dermal microthermal zones with
omy, precooling to maximize vasoconstriction, preservation of the stratum corneum. Fractional
aspiration before injection, reducing volume in ALs create multifocal columns of ablated (absent)
high-risk areas, and the use of a blunt cannula for tissue of the epidermis (including stratum cor-
injection. If vascular occlusion occurs, the injec- neum) and dermis. These columns are lined by a
tion should be discontinued immediately, warm thin coagulation layer.38
compress and massage should be instituted, topi- Nonlaser, light-based systems are a group
cal nitropaste should be applied to promote vaso- of devices that emit wavelengths in the visible
dilation, and hyaluronidase should be injected. and mid or near infrared ranges. These include
Currently, hyaluronidase for this purpose is not intense pulsed light and light-emitting diodes.
approved by the FDA and is considered off-label. Intense pulsed light uses a range of light wave-
lengths; lasers use only 1 wavelength. These
Energy-Based Devices modalities include dermal remodeling without
Indications epidermal ablation.39
There are several laser and nonlaser energy- Non–light-based systems include fractional
based devices, both ablative and nonablative, avail- radiofrequency microneedling and ultrasound-
able for facial rejuvenation. The specific modality based devices (Table 3). The former entails
should be tailored to the patient’s characteristics, radiofrequency-generated thermal energy in
preferences, and goals.37,38 Indications generally microsecond pulses through fine, insulated or
involve addressing mimetic rhytides, dyschromias, noninsulated electrodes that selectively heat the
precancerous lesions, irregular photoaged skin, dermis while sparing the epidermis.38 Thermal
scars, freckles, and melasma. injury elicits collagen and elastin production and
fibroblast remodeling. Ultrasound modalities
Contraindications deliver focused sound beams to specific spots on
Each device and technique has contraindica- the skin and cause invisible wounds that stimulate
tions. These devices generally are contraindicated collagen and elastin synthesis in the surrounding
in patients with active acne; open sores or wounds; skin.
active localized infections, including herpes labia-
lis; moderate to severe chronic skin conditions, Profile
such as psoriasis or eczema; extreme personal The energy-based device market is large and
history of keloids; or immunosuppression. Care continuously expanding. Comprehensive infor-
should be taken in patients with concomitant che- mation on each system, including FDA clearance
modenervation (neurotoxin) injections to avoid and key features including spot sizes, wavelengths,
undesirable toxin diffusion. Ablative resurfacing target chromophores, operating modes, typical
lasers are contraindicated in Fitzpatrick type V or treatment duration, and postoperative recovery,
VI skin.39 can be found on the manufacturer’s website.
Mechanism of Action Outcomes
Light amplification by stimulated emission of Multiple studies have evidenced the success
radiation works with a medium (solid, liquid, gas), of energy-based devices in the treatment of pho-
an optical chamber, and an energy source. Specific toaging and scarring. (See Table, Supplemental
chromophores are often targeted in the tissue Digital Content 4, which demonstrates level 1

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 Volume 154, Number 4 • Noninvasive Treatments of the Aging Face

Table 3. Nonlaser, Nonlight Energy-Based Devices

Monopolar Focused Ultrasound Fractional
Radiofrequency Dermal Dermal Remodeling Radiofrequency Subcutaneous Dermal
Remodeling (Thermage) (Ultherapy) Microneedling (Secret) Radiotherapy (Thermi)
Indication Skin tightening Skin tightening and lifting Skin tightening Frown lines
Mechanism Simultaneous heating Microfocused ultrasound Uses extrafine micronee- Temporary nerve ablation
using radiofrequency in heating and denaturing dles to promote collagen (up to 2 years) using
the deep dermal layer collagen in deep reticu- remodeling by heating radiofrequency needle
and cooling of epidermis lar dermis, stimulating the dermis stimulation
new collagen synthesis
Advantages Preserves the epidermis FDA-approved to treat Longer lasting compared
contour deformities with botulinum toxin
in the head and neck
region
Disadvantages Possible pain and fat Moderate results, mild Pain, bleeding, possible Pain, erythema, edema in
atrophy, subtle results edema, tingling, hyperpigmentation, the treatment region
tenderness, numbness, subtle results
possible bruising

and 2 evidence of energy-based devices for treat- sun avoidance and sunscreen before treatment
ment of the aging face, http://links.lww.com/PRS/ for several weeks with topical tretinoin and hydro-
H43.)41–45 Mild to moderate rhytides can be man- quinone, and occasionally after treatment with
aged with both ALs and fractionated lasers, with acyclovir and moisturizers.
greater effects but longer downtimes with ALs.39 A superficial peel is suitable for conditions in
Radiofrequency and ultrasound devices can the epidermis, such as fine rhytides, and mild dys-
improve rhytides.39 chromia, such as lentigos. The main advantage of
superficial peels is that they are well tolerated with
AEs and Complications minimal recovery. A medium peel can address
Safe and effective use of devices entails under- conditions in both the epidermis and superficial
standing the histologic laser–tissue interaction.38 layer of the dermis. This can better address photo-
Depending on the provider and device, potential damage and fine rhytides. A deep peel, although
AEs include pain, edema, photosensitivity, per- falling out of favor due to the development of
sistent erythema, wounds, infections, and postin- lasers, has been used historically to target more
flammatory hyper- or hypopigmentation.46 advanced skin photoaging, deep rhytides, and
hyperpigmentation.47–50
Peels
Indications Contraindications
Chemical or mechanical peels promote Active infection, dermatitis, history of radia-
skin tightening through controlled damage tion at the application site, comorbidities or
of the skin. These are widely used in rejuvenat- medications that cause aberrant or delayed wound-
ing photoaging of skin, acne, and dyspigmenta- healing process, and malnutrition are common
tion. Chemical peels are a relatively inexpensive contraindications. Patients with a history of hyper-
method of achieving a predictable, quick, and trophic scarring or keloid formation or pregnant
uniform depth of skin resurfacing by injuring the women should also avoid medium or deep peel.
epidermis or dermis. This in turn leads to a pre- A relative contraindication includes smoking or
dictable pattern of healing, resulting in the regen- nicotine use, which may impair healing. Phenol is
eration of the epidermis and parts of the dermis. relatively contraindicated in patients with hepatic
There are a variety of agents that can be tai- or renal disease as it is metabolized in the liver
lored to each patient’s needs (Table 4). The and excreted by the kidneys.
choice is dependent on the patient’s concerns, Mechanism of Action
Fitzpatrick type, amount of actinic damage, recov- Chemical peels induce keratolysis, keratoco-
ery time, and aesthetic outcome. Peels are based agulation, and denaturation of proteins in the
upon the depth of their skin penetration, ranging dermal and epidermal layers. These processes
from superficial (from corneal to basal cell lay- stimulate the regeneration of keratinocytes,
ers of epidermis), to medium (to the papillary or reorganization of dermal connective tissues and
upper reticular dermis), to deep (down to midre- scaffold proteins important in structure, and pro-
ticular dermis).47–49 With many facial rejuvenation duction of collagen and elastin.47–50 Overall, these
procedures, conditioning is often performed with processes result in the improvement of superficial
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 Plastic and Reconstructive Surgery • October 2024

Table 4. Chemical Peels

Superficial Medium Depth Deep
Clinical use • Any Fitzpatrick skin type • Fitzpatrick skin type • Fitzpatrick skin type I–III
• Mild dyspigmentation I–IV • Glogau skin type III–V
• Melasma • Mild photoaging • Severe dyspigmentation
• Lesions of upper epidermal layer • Superficial rhytides • Lesions of deeper dermis,
• Penetrates to papil- penetrates to midreticular
lary dermis dermis
Agents AHA Jessner solution Salicylic acid TCA, low to medium • Phenol Hetter formula
• Glycolic acid concentrations • Phenol Baker-Gordon
• Tartaric acid formula
• Lactic acid • TCA, medium to high
• Malic acid concentrations
• Mandelic acid
• Pyruvic acid
Mechanism • Desquamation at Epidermolysis Desmolysis Coagulative necrosis Phenol causes keratocoagu-
low concentration causing protein lation; croton oil causes
• Epidermolysis at denaturation and epidermolysis
high concentration cell death
Potential Erythema, pruritus, burning, superficial epidermolysis Scar formation, Phenol can cause cardio-
complications milia, acneiform toxicity, nephrotoxicity,
eruptions, deeper hepatotoxicity
epidermolysis
AHA, alpha hydroxy acid; TCA, trichloroacetic acid.

or deep rhytides and dyspigmentation, making DISCUSSION

the skin appear more youthful.50,51 Pharmacologic and minimally invasive antiag-
Profile ing treatments can target different components of
Chemical peels are relatively inexpensive and facial aging, and continue to evolve. With continu-
achieve a uniform effect throughout the areas of ous research efforts, traditional treatments, such as
application. Commonly used agents are manufac- BoNTA, injectable fillers, and chemical peels, are
tured and sold by various companies. improving, with more effective and lasting results.
With the advancement of technologies, a wide vari-
Outcomes ety of energy-based devices can provide precise and
Chemical peel was the third most performed controlled targeting of skin components for more
nonsurgical cosmetic procedure in 2021 accord- predictable outcomes. Like traditional methods,
ing to the Aesthetic Society. Many authors have these can achieve skin tightening and resurfacing.
published their results using different combina- For soft-tissue descent and facial volume
tions of chemical agents, demonstrating their loss, surgery often remains the mainstay of treat-
effectiveness in improving rhytides,52–57 photo- ment. Rhytidectomy with fat grafting for volu-
aging,52–54 and patient satisfaction. (See Table, mization can provide dramatic improvements to
Supplemental Digital Content 5, which demon- facial anatomy and lasting results. However, for
strates level 1 and 2 evidence of chemical peels patients who are not candidates for surgery, or
for treatment of the aging face, http://links.lww. who are unwilling to undergo surgery, pharmaco-
com/PRS/H44.)52,53,56,58–64 logic and noninvasive therapies provide options
With adequate interval treatments, patients to address different components of facial aging.
can start appreciating the results as early as 4 For example, newer agents, such as deoxycholic
weeks.65 Long-term treatment has been shown acid (Kybella), an adipose cell cytolytic agent and
to improve skin hydration, elasticity, and mela- the only FDA-approved, nonsurgical treatment
nin index. Improvements in hydration and elas- for submental fat deposition, has been used to
ticity correlated to the number of treatments address moderate to severe convexity of fullness
received.57 associated with submental fat.66 Moreover, in July
AEs and Complications of 2020, the FDA approved oxymetazoline hydro-
In general, complications include scarring, chloride ophthalmic solution 0.1% for acquired
hyper- or hypopigmentation, bacterial infection, ptosis, which has been shown to improve upper
herpes simplex virus cutaneous reactivation, acne, eyelid position and scleral whiteness in clinical
or milia. Other complications are specific to the studies.67 As the demand for noninvasive and min-
chemicals used; for example, phenol may cause imally invasive aesthetic procedures continues to
cardiac dysrhythmia. grow, more options may become available.

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 Volume 154, Number 4 • Noninvasive Treatments of the Aging Face

Fig. 4. Regenerative bioaesthetics toolkit for skin and hair regeneration comprises cellular and acellular options. Various sources
for mesenchymal stem cells (cellular) and exosomes (acellular) include adipose tissue, bone marrow, and umbilical cord blood.

Regenerative bioaesthetics is an evolving no. NCT02526576 [http://www.clinicaltrials.

branch of regenerative therapies aimed at restor- gov/ct2/show/NCT02526576]).
ing youthful skin structure and function using Autologous fat grafting is frequently used in
innate reparative systems (Fig. 4). Stem cells aesthetic procedures, but is plagued by variabil-
are defined by their ability to self-renew and to ity in graft retention. Multiple studies have been
differentiate into various tissue lineages based published to support use of enrichment strate-
on their origin (embryonic versus induced plu- gies in fat grafts with products including platelet-
ripotent versus adult versus umbilical cord).68,69 rich plasma and ADSCs to improve retention.75
Currently, adult stem cells—specifically, adipose- Autologous SVF injected into each nasolabial fold
derived stem cells (ADSCs) and stromal vascular resulted in significant increase in dermal and sub-
fraction (SVF)—represent the most commonly cutaneous thickness and a decrease in wrinkling.76
used stem cells in aesthetics given ease of acces- Another study had similar findings using SVF gel
sibility, abundance, and sustained quality with injection to correct palpebromalar groove, tear-
age.70,71 However, these methods require fat har- trough deformity, and periorbital hollow.77 ADSCs
vesting (lipoaspirate), processing, and injection can stimulate fibroblasts and keratinocytes to
or grafting to the target area.72 These techniques proliferate and migrate, suggesting their ability
are variably considered minimally invasive. SVF to maintain epidermal organization and homeo-
contains a mixed composition of cells, includ- stasis.78–80 Antiaging effects of stem cells from adi-
ing preadipocytes, adipocytes, macrophages, pose tissue may result from glycation suppression,
endothelial progenitor cells, and ADSCs, that antioxidation, and trophic effects.81 ADSC charac-
are rich in growth factors.73 ADSCs represent a teristics and function may be influenced by host
multipotential stem-cell population that can dif- factors, such as obesity or the cellular microenvi-
ferentiate into adipogenic, osteogenic, chon- ronment, and warrant further investigation.75,82
drogenic, and other mesenchymal lineages.74 Potential side effects related to stem-cell rejec-
Further processing of ADSCs, including ADSCs tion, undesired immune response, unexpected cell
cultured in platelet-rich plasma, has shown thera- contamination, and unsatisfactory clinical effect
peutic benefit in skin, including facial fat graft- should be cautiously considered.83,84 There are cur-
ing (“Adipose Derived Stem Cells in Facial Fat rently no FDA-approved regenerative therapies
Grafting [SVF],” ClinicalTrials.gov identification for skin rejuvenation or hair restoration. As such,

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 Plastic and Reconstructive Surgery • October 2024

practicing at the forefront of regenerative medicine An Integrated Approach to Biochemistry and Product Development.
and aesthetic reconstructive surgery requires a rig- Norwich, NY: William Andrew, Inc; 2009:55–90.
5. Shin JW, Kwon SH, Choi JY, et al. Molecular mechanisms
orous approach to research and clinical validation. of dermal aging and antiaging approaches. Int J Mol Sci.
2019;20:2126.
6. Swift A, Liew S, Weinkle S, Garcia JK, Silberberg MB. The
CONCLUSIONS facial aging process from the “inside out.” Aesthetic Surg J.
Facial aging is a multifactorial and dynamic 2021;41:1107–1119.
process. Many minimally invasive options are avail- 7. Mendelson B, Wong CH. Changes in the facial skeleton with
able to address different aspects of facial aging. It aging: implications and clinical applications in facial rejuve-
nation. Aesthetic Plast Surg. 2012;36:753–760.
is important for clinicians to understand the goals 8. Dunlop N, Abramowicz S, Fisher E. Pharmacology of
of the patient and the benefits, risks, and limita- aesthetic medicines. Oral Maxillofac Surg Clin North Am.
tions of each option. A thorough analysis of each 2022;34:189–200.
patient should be performed to provide a tailored 9. Philipp-Dormston WG, Bertossi D, Houschyar K, Rahman
antiaging treatment with the correct combination E. Botulinum toxins for esthetic facial injections: a scientific
review to support evidence-based best practice. Facial Plast
of treatments to maximize outcomes. Surg. 2022;38:152–155.
Samir Mardini, MD 10. Brin M, James C, Maltman J. Botulinum toxin type A prod-
Division of Plastic Surgery ucts are not interchangeable: a review of the evidence.
Mayo Clinic Biologics 2014;8:227–241.
200 First Street SW 11. Crowley JS, Silverstein ML, Reghunathan M, Gosman AA.
Rochester, MN 55905 Glabellar botulinum toxin injection improves depression
[email protected] scores: a systematic review and meta-analysis. Plast Reconstr
Facebook: Mayo Clinic Minnesota Surg. 2022;150:211e–220e.
Plastic & Reconstructive Surgery Residency 12. Zargaran D, Zoller F, Zargaran A, et al. Complications
Instagram: @samirmardinimd, @mayoclinic of cosmetic botulinum toxin A injections to the upper
face: a systematic review and meta-analysis. Aesthet Surg J.
2022;42:NP327–NP336.
DISCLOSURE 13. Rahman E, Alhitmi HK, Mosahebi A. Immunogenicity to bot-
ulinum toxin type A: a systematic review with meta-analysis
Dr. Wyles is a consultant at Rion Aesthetics, LCC. across therapeutic indications. Aesthet Surg J. 2022;42:106–120.
The authors have no financial or commercial disclosures 14. Camargo CP, Xia J, Costa CS, et al. Botulinum toxin type A for
related to this article. facial wrinkles. Cochrane Database Syst Rev. 2021;5:CD11301.
15. Jia Z, Lu H, Yang X, et al. Adverse events of botulinum toxin
type A in facial rejuvenation: a systematic review and meta-
ACKNOWLEDGMENTS analysis. Aesthetic Plast Surg. 2016;40:769–777.
16. Glogau R, Kane M, Beddingfield F, et al. OnabotulinumtoxinA:
Dr. LeBrasseur’s laboratory receives funding from a meta-analysis of duration of effect in the treatment of gla-
the National Institutes of Health, National Institute on bellar lines. Dermatol Surg. 2012;38:1794–1803.
Aging (grants R01 AG055529, R33 AG058738, P01 17. Guo Y, Lu Y, Liu T, et al. Efficacy and safety of botulinum
AG062413, and U54 AG044170), and the Glenn toxin type A in the treatment of glabellar lines: a meta-
Foundation for Medical Research. The authors thank analysis of randomized, placebo-controlled, double-blind tri-
als. Plast Reconstr Surg. 2015;136:310e–318e.
Cynthia J. Beeler, MLS, AHIP, academic medical librar- 18. Taylor SC, Callender VD, Albright CD, Coleman J, Axford-
ian and assistant professor of medical education at Mayo Gatley RA, Lin X. AbobotulinumtoxinA for reduction of gla-
Clinic Libraries, for creating the search strategy and bellar lines in patients with skin of color: post hoc analysis of
conducting the systematic literature search; and Carl pooled clinical trial data. Dermatol Surg. 2012;38:1804–1811.
Clingman, MA, senior medical illustrator, Division of 19. Wang J, Rieder EA. A systematic review of patient-reported
outcomes for cosmetic indications of botulinum toxin treat-
Biomedical and Scientific Visualization, Department of ment. Dermatol Surg. 2019;45:668–688.
Education, Mayo Clinic, for the medical illustrations 20. Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K,
used in this article. Fernandez HH, Mari Z. Diffusion, spread, and migration of
botulinum toxin. Mov Disord. 2013;28:1775–1783.
21. Zargaran D, Zoller FE, Zargaran A, Mosahebi A.
REFERENCES Complications of facial cosmetic botulinum toxin A injec-
1. Walker LC, Herndon JG. Mosaic aging. Med Hypoth. tion: analysis of the UK Medicines & Healthcare Products
2010;74:1048–1051. Regulatory Agency registry and literature review. J Plast
2. Mast BA, ed. 6 Principles of facial aesthetics. In: Plastic Reconstr Aesthet Surg. 2022;75:392–401.
Surgery: A Practical Guide to Operative Care. New York: Thieme 22. Pavicic T. Calcium hydroxylapatite filler: an overview of
Medical Publishers; 2021. safety and tolerability. J Drugs Dermatol. 2013;12:996–1002.
3. Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E, 23. U.S. Food & Drug Administration. Premarket approval.
Zouboulis CC. Skin anti-aging strategies. Dermatoendocrinol. Published 2022. Available at: https://www.accessdata.fda.
2012;4:308–319. gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm.
4. Thakur R, Batheja P, Kaushik D, Michniak B. Structural and 24. Peng T, Hong W, Fang J, Luo S. The selection of hyaluronic
biochemical changes in aging skin and their impact on skin acid when treating with the nasolabial fold: a meta-analysis. J
permeability barrier. In: Dayan N, ed. Skin Aging Handbook: Cosmet Dermatol. 2022;21:571–579.

840e
Copyright © 2023 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 154, Number 4 • Noninvasive Treatments of the Aging Face

25. Ghaddaf AA, Alsharef JF, Alomari MS, et al. Botulinum 42. Liu T-M, Sun Y-M, Tang Z-Y, Li Y-H. Microneedle fractional
toxin type A for lower limb lengthening and deformity cor- radiofrequency treatment of facial photoageing as assessed
rection: a systematic review and meta-analysis. J Orthop Sci. in a split-face model. Clin Exp Dermatol. 2019;44:e96–e102.
2022;28:806–813. 43. Li YH, Wu Y, Chen JZS, et al. A split-face study of intense
26. Stefura T, Kacprzyk A, Droś J, et al. Tissue fillers for pulsed light on photoaging skin in Chinese population.
the nasolabial fold area: a systematic review and meta- Lasers Surg Med. 2010;42:185–191.
analysis of randomized clinical trials. Aesthetic Plast Surg. 44. Chew J, Gin I, Rau KA, Amos DB, Bridenstine JB. Treatment
2021;45:2300–2316. of upper lip wrinkles: a comparison of 950 μsec dwell time
27. Czumbel LM, Farkasdi S, Gede N, et al. Hyaluronic acid is an carbon dioxide laser with unoccluded Baker’s phenol chem-
effective dermal filler for lip augmentation: a meta-analysis. ical peel. Dermatol Surg. 1999;25:262–266.
Front Surg. 2021;8:681028. 45. Stem RS, Dover JS, Levin JA, Arndt KA. Laser therapy ver-
28. Wang C, Luan S, Panayi AC, Xin M, Mi B, Luan J. Effectiveness sus cryotherapy of lentigines: a comparative trial. J Am Acad
and safety of hyaluronic acid gel with lidocaine for the Dermatol. 1994;30:985–987.
treatment of nasolabial folds: a systematic review and meta- 46. Manuskiatti W, Fitzpatrick RE, Goldman MP. Long-term
analysis. Aesthetic Plast Surg. 2018;42:1104–1110. effectiveness and side effects of carbon dioxide laser
29. Huang X, Liang Y, Li Q. Safety and efficacy of hyaluronic resurfacing for photoaged facial skin. J Am Acad Dermatol.
acid for the correction of nasolabial folds: a meta-analysis. 1999;40:401–411.
Eur J Dermatol. 2013;23:592–599. 47. Starkman SJ, Mangat DS. Chemical peel (deep, medium,
30. Haidar R, Freytag DL, Frank K, et al. Quantitative analysis light). Facial Plast Surg Clin North Am. 2020;28:45–57.
of the lifting effect of facial soft-tissue filler injections. Plast 48. Berson DS, Cohen JL, Rendon MI, Roberts WE, Starker I,
Reconstr Surg. 2021;147:765e–776e. Wang B. Clinical role and application of superficial chemical
31. Bhojani-Lynch T, Deckers A, Ohanes O, Poupard K, Maffert peels in today’s practice. J Drugs Dermatol. 2009;8:803–811.
P. A prospective, observational registry study to evaluate 49. Anitha B. Prevention of complications in chemical peeling. J
effectiveness and safety of hyaluronic acid-based dermal Cutan Aesthet Surg. 2010;3:186–188.
fillers in routine practice: interim analysis results with one 50. Soleymani T, Lanoue J, Rahman Z. A practical approach to
year of subject follow-up. Clin Cosmetic Investig Dermatol. 2021; chemical peels: a review of fundamentals and step-by-step
14:1685–1695. algorithmic protocol for treatment. J Clin Aesthet Dermatol.
32. Razavian E, Tehrani S. Evaluating the safety and efficacy of 2018;11:21–28.
a highly viscous 33-mg/ml hyaluronic acid volumizing filler 51. Hassan KM, Benedetto AV. Facial skin rejuvenation: ablative
in the treatment of facial wrinkles: an open-labeled, clinical laser resurfacing, chemical peels, or photodynamic therapy?
trial. Galen Med J. 2019;8:e1148. Facts and controversies. Clin Dermatol. 2013;31:737–740.
33. Galadari H, van Abel D, Al Nuami K, Al Faresi F, Galadari 52. Sun W, Zhang C, Zhao J, Wu J, Xiang L. Comparison of mod-
I. A randomized, prospective, blinded, split-face, single- erate and high energy of a nano-fractional radiofrequency
center study comparing polycaprolactone to hyaluronic treatment on a photoaging hairless mice model. Dermatol
acid for treatment of nasolabial folds. J Cosmet Dermatol. Surg. 2018;44:569–575.
2015;14:27–32. 53. Sitohang IB, Legiawati L, Suseno LS, Safira FD.
34. Jeong GJ, Ahn GR, Park SJ, Hong JY, Kim BJ. A random- Trichloroacetic acid peeling for treating photoaging: a sys-
ized, patient/evaluator-blinded, split-face study to compare tematic review. Dermatol Res Pract. 2021;2021:1–6.
the efficacy and safety of polycaprolactone and polynucleo- 54. Wambier CG, Lee KC, Soon SL, et al.; International Peeling
tide fillers in the correction of crow’s feet: the latest bios- Society. Advanced chemical peels: phenol-croton oil peel. J
timulatory dermal filler for crow’s feet. J Cosmet Dermatol. Am Acad Dermatol. 2019;81:327–336.
2020;19:1593–1599. 55. Langsdon PR, Milburn M, Yarber R. Comparison of the laser
35. U.S. Food & Drug Administration. Unintentional injec- and phenol chemical peel in facial skin resurfacing. Arch
tion of soft tissue filler into blood vessels in the face: FDA Otolaryngol Head Neck Surg. 2000;126:1195–1199.
safety communication. Published May 28, 2015. Available 56. Kitzmiller W. Comparison of a series of superficial chemical
at: https://www.fdanews.com/ext/resources/files/06- peels with a single midlevel chemical peel for the correction
15/06-08-15-filler.pdf?1433177462. Accessed November 6, of facial actinic damage. Aesthet Surg J. 2003;23:339–344.
2022. 57. Kubiak M, Mucha P, Rotsztejn H. Comparative study of 15%
36. Cohen JL. Understanding, avoiding, and managing dermal trichloroacetic acid peel combined with 70% glycolic acid
filler complications. Dermatol Surg. 2008;34:S92–S99. and 35% trichloroacetic acid peel for the treatment of pho-
37. Heitmiller K, Ring C, Saedi N, Biesman B. Nonsurgical light todamaged facial skin in aging women. J Cosmet Dermatol.
and energy–based devices. Facial Plast Surg Clin North Am. 2020;19:137–146.
2021;29:323–334. 58. Alam M, Omura NE, Dover JS, Arndt KA. Glycolic acid
38. Chen SX, Cheng J, Watchmaker J, Dover JS, Chung HJ. peels compared to microdermabrasion: a right-left con-
Review of lasers and energy-based devices for skin rejuvena- trolled trial of efficacy and patient satisfaction. Dermatol Surg.
tion and scar treatment with histologic correlations. Dermatol 2002;28:475–479.
Surg. 2022;48:441–448. 59. Yildirim S, Gurel MS, Gungor S, Tekeli O, Canat D.
39. Britt CJ, Marcus B. Energy-based facial rejuvenation. JAMA Comparison of efficacy of chemical peeling with 25% tri-
Facial Plast Surg. 2017;19:64–71. chloroacetic acid and 0.1% retinoic acid for facial rejuvena-
40. Gold MH. Update on fractional laser technology. J Clin tion. Adv Dermatol Allergol. 2016;3:199–205.
Aesthet Dermatol. 2010;3:42–50. 60. Holzer G, Pinkowicz A, Radakovic S, Schmidt JB, Tanew
41. Hu S, Atmakuri M, Rosenberg J. Adverse events of nonab- A. Randomized controlled trial comparing 35% trichloro-
lative lasers and energy-based therapies in subjects with acetic acid peel and 5-aminolaevulinic acid photodynamic
Fitzpatrick skin phototypes IV to VI: a systematic review and therapy for treating multiple actinic keratosis. Br J Dermatol.
meta-analysis. Aesthet Surg J. 2022;42:537–547. 2017;176:1155–1161.

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Copyright © 2023 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Plastic and Reconstructive Surgery • October 2024

61. Bagatin E, Parada MOB, Miot HA, Hassun KM, Michalany lipoaspirates from different subcutaneous adipose tissue
N, Talarico S. A randomized and controlled trial about depots. Aesthet Surg J. 2016;36:831–841.
the use of oral isotretinoin for photoaging. Int J Dermatol. 74. Locke M, Feisst V, Dunbar PR. Concise review: human
2010;49:207–214. adipose-derived stem cells: separating promise from clinical
62. Kim H, Kim N, Jung S, et al. Improvement in skin wrinkles need. Stem Cells 2011;29:404–411.
from the use of photostable retinyl retinoate: a randomized 75. Vyas KS, Vasconez HC, Morrison S, et al. Fat graft enrich-
controlled trial. Br J Dermatol. 2010;162:497–502. ment strategies: a systematic review. Plast Reconstr Surg.
63. Stiller MJ, Bartolone J, Stern R, et al. Topical 8% glycolic 2020;145:827–841.
acid and 8% L-lactic acid creams for the treatment of pho- 76. Amirkhani MA, Shoae-Hassani A, Soleimani M, Hejazi S,
todamaged skin: a double-blind vehicle-controlled clinical Ghalichi L, Nilforoushzadeh MA. Rejuvenation of facial skin
trial. Arch Dermatol. 1996;132:631–636. and improvement in the dermal architecture by transplanta-
64. Leyden JJ, Grove GL, Grove MJ, Thorne EG, Lufrano L. tion of autologous stromal vascular fraction: a clinical study.
Treatment of photodamaged facial skin with topical treti- Bioimpacts. 2016;6:149–154.
noin. J Am Acad Dermatol. 1989;21:638–644. 77. Jiang S, Quan Y, Wang J, Cai J, Lu F. Fat grafting for facial
65. Kubiak M, Mucha P, Dębowska R, Rotsztejn H. Evaluation rejuvenation using stromal vascular fraction gel injection.
of 70% glycolic peels versus 15% trichloroacetic peels for Clin Plast Surg. 2020;47:73–79.
the treatment of photodamaged facial skin in aging women. 78. Hassan WU, Greiser U, Wang W. Role of adipose-derived stem
Dermatol Surg. 2014;40:883–891. cells in wound healing. Wound Repair Regen. 2014;22:313–325.
66. Shamban AT. Noninvasive submental fat compartment treat- 79. Stessuk T, Puzzi MB, Chaim EA, et al. Platelet-rich plasma
ment. Plast Reconstr Surg Glob Open 2016;4:e1155. (PRP) and adipose-derived mesenchymal stem cells: stimula-
67. Ugradar S, Kim JS, Trost N, et al. Changes to eye whiteness tory effects on proliferation and migration of fibroblasts and
and eyelid/brow position with topical oxymetazoline in aes- keratinocytes in vitro. Arch Dermatol Res. 2016;308:511–520.
thetic patients. Aesthet Surg J. 2022;42:582–589. 80. Son WC, Yun JW, Kim BH. Adipose-derived mesenchymal
68. Morrison SJ, Spradling AC. Stem cells and niches: mecha- stem cells reduce MMP-1 expression in UV-irradiated human
nisms that promote stem cell maintenance throughout life. dermal fibroblasts: therapeutic potential in skin wrinkling.
Cell 2008;132:598–611. Biosci Biotechnol Biochem. 2015;79:919–925.
69. Wu J, Izpisua Belmonte JC. Stem cells: a renaissance in 81. Zhang S, Dong Z, Peng Z, Lu F. Anti-aging effect of adipose-
human biology research. Cell 2016;165:1572–1585. derived stem cells in a mouse model of skin aging induced
70. Godic A. The role of stem cells in anti-aging medicine. Clin by D-galactose. PLoS One 2014;9:e97573.
Dermatol. 2019;37:320–325. 82. Vyas KS, Bole M, Vasconez HC, et al. Profile of adipose-
71. Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived derived stem cells in obese and lean environments. Aesthetic
stem cells in regenerative medicine. Transfus Med Hemother. Plast Surg. 2019;43:1635–1645.
2016;43:268–274. 83. Herberts CA, Kwa MS, Hermsen HP. Risk factors in the
72. Shridharani S, Broyles J, Matarasso A. Liposuction devices: development of stem cell therapy. J Transl Med. 2011;9:29.
technology update. Med Devices Evid Res. 2014:241. 84. McArdle A, Senarath-Yapa K, Walmsley GG, et al. The
73. Grasys J, Kim BS, Pallua N. Content of soluble factors role of stem cells in aesthetic surgery. Plast Reconstr Surg.
and characteristics of stromal vascular fraction cells in 2014;134:193–200.

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