Review Article

Journal of Cosmetic Dermatology, 15, 82--88

Facial rejuvenation starts in the midface: three-dimensional

volumetric facial rejuvenation has beneficial effects on nontreated
neighboring esthetic units
Uwe Wollina, MD
Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany

Summary Facial aging is a major indication for minimal invasive esthetic procedures. Dermal
fillers are a cornerstone in the approach for facial sculpturing. But where to start?
Our concept is midfacial volume restoration in first place. This will result in a healthy
and youthful appearance creating a facial V-shape. But midfacial filler injection does
not only improve the malar area. It has also beneficial effects on neighboring esthetic
units. We report on such improvements in periocular and nasolabial region, upper
lips and perioral tissue, and the jaw line and discuss anatomical background. We
hypothesize that midfacial deep filler injections also may activate subdermal white
adipose tissue stem cells contributing to longer lasting rejuvenation.
Keywords: facial aging, midfacial sculpturing, dermal fillers, hyaluronic acid, calcium
hydroxylapatite, adipose tissue

three-dimensional volumetric approach is indispens-

Introduction
The use of neurotoxins and dermal fillers revolution-
ized facial nonsurgical rejuvenation. As by a recent
analysis in the United States, dermatologists are most
forefront in this approach. The numbers of treatments
and the number of patients treated are rising in the
last decade in contrast to surgical procedures such as
face lift.1
Aging is characterized by superficial changes of skin
color and texture. But more pronounced alterations
are found in the deeper tissue layers such as bone,
facial muscles, and subcutaneous adipose tissue.2
Facial aging is a robust health indicator.3
The correction of facial changes caused by external
and internal aging aims at a youthful and healthy,
natural appearance. For an optimized rejuvenation, a
able. When using filler treatments, a detailed knowl-
edge of facial anatomy, filler qualities, and injection
techniques is necessary to avoid unwanted side
effects.4 Although every patient has individual needs,
midfacial treatment is of particular importance to
achieve a youthful appearance. Therefore, rejuvenation
procedures should start from here and be supple-
mented as needed.
In the following, we will focus on an often over-
looked beneficial effect of the three-dimensional tech-
nique on neighboring esthetic units. With a conscious
use of this knowledge, esthetic improvement can be
achieved while avoiding injections in the more risky or
painful areas.
Fillers

Correspondence: Uwe Wollina, Department of Dermatology and Allergol- There is a broad range of fillers composed of a variety
ogy, Academic Teaching Hospital Dresden-Friedrichstadt, Friedrichstrasse of materials on the international market.5 With respect
41, 01067 Dresden, Germany. E-mail: wollina-uw@khdf.de to filler material, we are focusing on hyaluronic acid
Accepted for publication July 23, 2015 (HA)-based fillers and biostimulant filler containing cal-

82 © 2015 Wiley Periodicals, Inc.


cium hydroxylapatite (CaHA; Radiesseâ), which may
induce increased collagen production in vivo.6
HA fillers can be characterized by physical proper-
ties, HA content, and cross-linking. Major physical
qualities are described by the elastic modulus G’, the
viscous modulus G’’, complex viscosity N*, shear force,
and shear thinning.7 Based on the composition, one
can differentiate between biphasic (such as Restylaneâ
or Perlaneâ) and monophasic (such as Teoxaneâ or
Beloteroâ) fillers. Cross-linking agents are 1,4-butane-
diol diglycidyl ether, divinyl sulfone, and 2, 7,
8-diepoxyoctane.8 Longevity of fillers depends on HA
content, cross-linking, injection site, and technique.9
Less hydrated fillers will have a lifting activity after fil-
ler placement as they continue to absorb larger quanti-
ties of fluid after placement. This could be an
advantage for midfacial injections as the injection vol-
ume can be lower.10 The longevity of HA filler depends
on various aspects with a range of up to
18 months.8,11
CaHA filler Radiesseâ is composed of carboxymethyl-
cellulose gel and 30% of calcium hydroxylapatite parti-
cles of 25–45 lm diameter. This filler is approved for
medium to deep facial lines and folds and for correc-
tion of facial volume loss in HIV-related lipoatrophy.
Deep injections are recommended to avoid formation of
visible or palpable nodules.9 It acts as a scaffold for
connective tissue ingrowth and lasts for about
15–24 months.12 This filler stimulates significantly
more collagen and elastin production and angiogenesis
compared to HA fillers.13 Although there is an immedi-
ate lifting effect after injection, skin tightening occurs
with some delay. CaHA is best placed deep in the sub-
dermal plane.9
Two-dimensional versus three-dimensional
injection technique
Fillers are used for decades in esthetic medicine to
improve facial appearance. The two-dimensional
approach focuses on elevation of deep folds, such as
the nasolabial fold. This is performed with injections
under the deepest lines to lift up the folds. Such tech-
nique still is a cornerstone in randomized controlled
trials to evaluate new fillers. Significant improvement
of Wrinkle Severity Scale was documented.14–19 Ran-
domized controlled trials with hyaluronic acid (HA) fil-
ler have also demonstrated a very good safety profile
with skilled users.20
In contrast to the former, three-dimensional volu-
metric technique does not focus on folds and furrows
but esthetic units.11,21 The principal domain of the
© 2015 Wiley Periodicals, Inc.
Midfacial rejuvenation . U Wollina
technique is midfacial rejuvenation, although it repre-
sents a universal approach.22–25
Studying adipose tissue compartments in aging face
by cadaveric studies demonstrated decreased size of
adipocytes in the deep facial fat compartments and a
loss of volume compared to superficial compartments.
Therefore, a fill and lift attempt of this compartment to
restore a youthful face has been propagated.26
Safety issues
The malar region is a relatively safe are for filler infec-
tions and less prone to bruising or nodule formation.
Attention must be paid to the foramen infraorbitale.
This is the area where the infraorbital artery anasto-
moses with the facial artery. The same is true for the
corresponding veins. The infraorbital nerve reaches the
malar region through the infraorbital foramen together
with the vessels. The infraorbital foramen lies in the
mediopupillary line about one cm inferior to the
infraorbital margin.27 Here, no filler placement should
be carried out to avoid vascular or nerve damage or
unintended intra-arterial filler injection with possible
catastrophic sequelae.28
Evidence for beneficial effects of three-
dimensional volumetric midfacial filler
injection on neighboring esthetic units
Deep mediolateral malar bolus injection and nasolabial
folds
More than 20 years ago, Owsley suggested to move
the malar fat pad craniolaterally to improve nasolabial
folds.29 Instead of the surgical approach, the liquid lift
technique with fillers addresses the same problem from
a different angle (Figs 1 and 2).
In a randomized split-face study comparing three dif-
ferent injection techniques for improvement of nasola-
bial folds, the authors reported a similar improvement
by low-volume deep bolus into mediolateral cheek vs.
injection beneath the fold or the combination of both.
The latter, however, needed the highest injection vol-
ume. In this study, patients preferred the deep bolus
injection although the difference did not reach statisti-
cal significance.30 The deep mediolateral cheek bolus
injection offers another advantage, that is the volumiz-
ing of the malar region. This technique also respects
anatomical peculiarities associated with facial folds. A
recent anatomical study identified a major lymphatic
vessel and its surrounding tube of adipose tissue within
1 mm of the fold.31 Unintentional lymphatic filler
83
Midfacial rejuvenation . U Wollina
(a)
Figure 1 Sixty-years-old female. (a) Before treatment. (b) Monophasic HA filler in the malar area. Improvement of nasolabial folds,
re-establishment of the youthful facial upright triangle (V-shape) and diminution of down-turn of the corners of the mouth.
(a)
Figure 2 Forty-nine-years-old female. (a) Before treatment. (b) After malar augmentation with calcium hydroxylapatite filler improve-
ment of nasolabial fold and marionette line.
injection can be avoided by deep bolus in a distance
from the nasolabial fold. This area is also highly vascu-
larized by blood vessels. Accidental intra-arterial injec-
tion would result in tissue necrosis. This is of clinical
importance, as nasolabials are the second most com-
mon site for skin necrosis following filler injection.32
Deep malar bolus injection offers the opportunity for
long-term volumizing effects. Magnetic resonance
imaging analysis suggested capsule formation, fibrosis,
and ossification after HA filler injections close to the
bone.33 MRI demonstrates CaHA particles after deep
injections, but controls after 2.5 years demonstrated a
complete biodegradation of the product.34 Activation of
adipose tissue-derived mesenchymal stem cells could
explain the long-lasting effects of the procedure.35
Improvement of the malar region improves self-confi-
dence and facial attractiveness in female patients.36
Deep malar filler injections and periocular rejuvenation
The lower lid is one of the most risky areas for filler
injections. Bruising, visible nodule, or granuloma for-
84
(b)
(b)
mation are well-known undesired effects. Tear trough
deformities are associated with aging and comprise
relaxation, atrophy, and ptosis. The anatomical basis
of tear trough (nasojugeal fold) represents the septum
orbitale that marks the border between the loose tissue
of the lower lid and the malar region.37,38
Filler injections superficial to the malar septum can
impede lymphatic flow. Fillers with very high lifting
capacity (as measured by elastic modulus G’) accumu-
lated more fluid increasing the risk of secondary lym-
phatic edema. Injections close to the periosteum of the
bone reduce the risk of embolization and bruising, as
there is an avascular space.39,40
In middle-aged women, a deep malar augmentation
by filler can improve the tear trough (Fig. 3). The
effect is mediated by the septum orbitale. A 2012 con-
sensus conference on periocular rejuvenation recom-
mended that restoration of the midface is the first
essential step because treatment for the malar area has
the most significant positive impact. It is “important to
restore the malar contour, as malar volume anchors
the structure of the midface. Secondly, an assessment
© 2015 Wiley Periodicals, Inc.
 Midfacial rejuvenation . U Wollina

(a) (b)

Figure 3 Fifty-two-years-old female with tear trough and periorbital hollows (a). (b) After malar augmentation with calcium hydroxyla-
patite filler marked improvement of tear trough and periorbital hollows.

of the effects of malar enhancement on the appearance
of the nasolabial folds and the nasojugal fold (tear
trough) should be conducted because these aging signs
may be decreased by malar enhancement. Finally,
treatment for the nasolabial folds and periorbital area
with HA should be performed when needed.”41
Malar augmentation and the upper lip
Perioral subcutaneous adipose tissue has only thin
fibrous septations.42 Superficial malar tissue injections
will not have effects on upper lip. Nevertheless, we
have recently demonstrated that augmentation of the
malar bone and midface by deep injections of HA fillers
can improve the appearance of upper lip with an
increased show of the white roll (Fig. 4). In patients
with thin lips, however, this effect will be negligible.43
This is probably due to changes in superficial musculo-
aponeurotic system (SMAS) and nasolabial fold.44 It
has been demonstrated that the zygomaticus muscles
adhere to the nasolabial fat pad.45 Thereby, the muscle
will be indirectly affected by volume restoration of that
fad pad. The deep medial cheek fat pad is localized
medial to the zygomaticus muscle. Volume restoration
in this compartment will have less effects on the zygo-
maticus muscle.
Malar augmentation avoids the risk of unintended
filler injection into superior labial artery. Nevertheless,
lip augmentation with soft fillers along the vermillion
border is safe.46
Malar augmentation and the jaw line
The jaw line defines the lower border of the face later-
ally. By descent of the overlying fat pads and loosening
of the mandibular septum, “jowling” develops as an
aging sign. Jowl ptosis and loss of submalar hollow are
important features.47 Volume replacement of the malar
area induces a lifting effect that affects not only frontal
but lateral components as well (Figs 5 and 6).
The correction of the esthetic jaw line often needs
additional attempts. To reduce caudal-oriented platys-
mal forces, botulinum toxin is effective. Stimulation of
connective tissue renewal and tissue tightening can
also be achieved by CaHA injection along the mandible
and for the prejowl sulcus.25

(a) (b)

Figure 4 A 65-years-old female with tear trough, malar lines, and prominent nasolabial folds (a). (b) Immediately after malar augmen-
tation with calcium hydroxylapatite, a marked improvement of all components of facial aging is visible. There is also a slight effect on
the upper lip.

© 2015 Wiley Periodicals, Inc. 85

Midfacial rejuvenation . U Wollina
(a)
Figure 5 (a) Prominent nasolabial folds, prejowl sulcus, and “jowling” in a 65-years-old female. (b) Immediately after malar augmenta-
tion by calcium hydroxylapatite marked improvement of the jaw line. The marionette lines were treated by monophasic filler.
(a)
Figure 6 (a) Prominent “jowling” and multiple fine lines on the cheeks in an 84-years-old female. (b) Immediate improvement of lines
and the esthetic jaw line by calcium hydroxylapatite.
Discussion
Facial aging has several aspects which are not limited
to soft tissue alone. Cardinal features include loss of
volume – which is most prominent in the midface –
and cheek flaccidity leading to “jowling” that is most
prominent in the midface and lower face. There is for-
mation of dynamic and static lines and superficial
changes including pigment changes, vascular ectasias,
and epidermal keratoses.48,49
Facial rejuvenation with fillers is a popular minimal
invasive approach to combat clinical sign of facial aging.
Correction of midfacial volume loss by deep suprape-
riostal filler placement has become a reliable method for
a youthful facial appearance. With this technique, a pro-
longed filler efficacy has been observed for HA filler and
CaHA. This cannot be explained solely on the base of less
influence of mimic musculature. There is some evidence
to support activation of somatic stem cells of the deep fat
compartment as discussed elsewhere.35
As demonstrated here, the deep midfacial filler injec-
tion has also some beneficial effects on neighboring
86
(b)
(b)
esthetic units such as tear trough deformity, nasola-
balial folds, and upper lip position. These effects hap-
pen without touching these risky and /or painful areas
for injection. This will also reduce the amount of filler
necessary for the desired clinical improvement. The
observation underlines the importance of subcutaneous
fat pads and three-dimensional retaining ligaments in
facial aging.26,50
In the planning of facial rejuvenation, the first step
should be the correction of midfacial volume loss.
Midfacial filler injection is a cornerstone for improve-
ment of facial appearance and a natural youthful look.
It offers long-lasting effects probably related to the acti-
vation of subdermal white adipose tissue stem cells.35
References
1 Sandoval LF, Huang KE, Davis SA et al. Trends in the use
of neurotoxins and dermal fillers by US physicians. J Clin
Aesthet Dermatol 2014; 7: 14–9.
2 Gerth DJ. Structural and volumetric changes in the aging
face. Facial Plast Surg 2015; 31: 3–9.
© 2015 Wiley Periodicals, Inc.

3 Chen W, Qian W, Wu G et al. Three-dimensional human
facial morphologies as robust aging markers. Cell Res
2015; 25: 574–87.
4 Kulichova D, Borovaya A, Ruzicka T et al. Understanding
the safety and tolerability of facial filling therapeutics.
Expert Opin Drug Saf 2014; 13: 1215–26.
5 Wollina U, Goldman A. Dermal fillers: facts and contro-
versies. Clin Dermatol 2013; 31: 731–6.
6 Wang F, Garza LA, Kang S et al. In vivo stimulation of de
novo collagen production caused by cross-linked hyaluro-
nic acid dermal filler injections in photodamaged human
skin. Arch Dermatol 2007; 143: 155–63.
7 Santoro S, Russo S, Argenzio V et al. Rheological proper-
ties of cross-linked hyaluronic acid dermal fillers. J Appl
Biomater Biomech 2011; 9: 127–36.
8 Wollina U, Goldman A. Hyaluronic acid dermal fillers:
safety and efficacy for the treatment of wrinkles, aging
skin, body sculpturing and medical conditions. Clin Med
Rev Ther 2011; 3: 107–21.
9 Alam M, Gladstone H, Kramer EM et al. ASDS guidelines
of care: injectable fillers. Dermatol Surg 2008; 34:
115–48.
10 Stocks D, Sundaram H, Michaels J et al. Rheological eval-
uation of the physical properties of hyaluronic acid der-
mal fillers. J Drugs Dermatol 2011; 10: 974–80.
11 Raspaldo H. Volumizing effect of a new hyaluronic acid
sub-dermal facial filler: a retrospective analysis based on
102 cases. J Cosmet Laser Ther 2008; 10: 134–42.
12 Jansen DA, Graivier MH. Evaluation of a calcium hydrox-
ylapatite-based implant (Radiesse) for facial soft-tissue
augmentation. Plast Reconstr Surg 2006; 118 (Suppl 3):
22S–30S.
13 Yutskovskaya Y, Kogan E, Leshunov E. A randomized,
split-face, histomorphologic study comparing a volumetric
calcium hydroxylapatite and a hyaluronic acid-based der-
mal filler. J Drugs Dermatol 2014; 13: 1047–52.
14 Galadari H, van Abel D, Al Nuami K et al. A randomized,
prospective, blinded, split-face, single-center study com-
paring polycaprolactone to hyaluronic acid for treatment
of nasolabial folds. J Cosmet Dermatol 2015; 14: 27–32.
15 Hyun MY, Lee Y, No YA et al. Efficacy and safety of injec-
tion with poly-L-lactic acid compared with hyaluronic
acid for correction of nasolabial fold: a randomized, evalu-
ator-blinded, comparative study. Clin Exp Dermatol 2015;
40: 129–35.
16 Shin SJ, Her Y, Yu DS et al. Twenty-four-week multicen-
ter, evaluator-blinded clinical study of the efficacy and
safety of a dextran filler in the treatment of nasolabial
folds. Dermatol Surg 2014; 40: 652–7.
17 Buntrock H, Reuther T, Prager W et al. Efficacy, safety,
and patient satisfaction of a monophasic cohesive poly-
densified matrix versus a biphasic nonanimal stabilized
hyaluronic acid filler after single injection in nasolabial
folds. Dermatol Surg 2013; 39: 1097–105.
18 Ahn JY, Lee SH, Park KY et al. Clinical comparison of
two hyaluronic acid-derived fillers in the treatment of
© 2015 Wiley Periodicals, Inc.
Midfacial rejuvenation . U Wollina
nasolabial folds: Mesoglowâ and IAL Systemâ. Int J
Dermatol 2012; 51: 601–8.
19 Goodman GJ, Bekhor P, Rich M et al. A comparison of
the efficacy, safety, and longevity of two different hya-
luronic acid dermal fillers in the treatment of severe naso-
labial folds: a multicenter, prospective, randomized,
controlled, single-blind, within-subject study. Clin Cosmet
Investig Dermatol 2011; 4: 197–205.
20 Huang X, Liang Y, Li Q. Safety and efficacy of hyaluronic
acid for the correction of nasolabial folds: a meta-analysis.
Eur J Dermatol 2013; 23: 592–9.
21 Glasgold M. Introduction to volumetric facial rejuvena-
tion. Facial Plast Surg 2015; 31: 10–4.
22 Barr SK, Benchetrit A, Sapijaszko M et al. Clinical evalua-
tion of a cross-linked hyaluronic cid dermal filler applied
for facial augmentation. J Drugs Dermatol 2015; 14:
19–23.
23 Macierzy nska A, Pierzchała E, Placek W. Volumetric tech-
niques: three-dimensional midface modeling. Postepy
Dermatol Alergol 2014; 31: 388–91.
24 Rzany B, Cartier H, Kestemont P et al. Full-face rejuvena-
tion using a range of hyaluronic acid fillers: efficacy,
safety, and patient satisfaction over 6 months. Dermatol
Surg 2012; 38: 1153–61.
25 Goldman A, Wollina U. Facial rejuvenation for
middle-aged women: a combined approach with
minimally invasive procedures. Clin Interv Aging 2010; 5:
293–9.
26 Wan D, Amirlak B, Rohrich R et al. The clinical impor-
tance of the fat compartments in midfacial aging. Plast
Reconstr Surg Glob Open 2014; 1: e92.
27 Pilsl U, Anderhuber F, Rzany B. Anatomy of the cheek:
implications for soft tissue augmentation. Dermatol Surg
2012; 38: 1254–62.
28 Wollina U, Goldman A, Naoum C. Side effects in aesthetic
medicine. Spectrum, management and avoidance. Hau-
tarzt 2013; 64: 155–62.
29 Owsley JQ. Lifting the malar fat pad for correction of
prominent nasolabial folds. Plast Reconstr Surg 1993; 91:
463–74.
30 Goodier M, Elm K, Wallander I et al. A randomized com-
parison of the efficacy of low volume deep placement
cheek injection vs. mid- to deep dermal nasolabial fold
injection technique for the correction of nasolabial folds.
J Cosmet Dermatol 2014; 13: 91–8.
31 Pessa JE, Nguyen H, John GB et al. The anatomical basis
for wrinkles. Aesthet Surg J 2014; 34: 227–34.
32 Ozturk CN, Li Y, Tung R et al. Complications following
injection of soft-tissue fillers. Aesthet Surg J 2013; 33:
862–77.
33 Mashiko T, Mori H, Kato H et al. Semipermanent volu-
mization by an absorbable filler: onlay injection technique
to the bone. Plast Reconstr Surg Glob Open 2013; 1: pii:
e4-e14.
34 Pavicic T. Complete biodegradable nature of calcium
hydroxylapatite after injection for malar enhancement:
87
Midfacial rejuvenation . U Wollina
an MRI study. Clin Cosmet Investig Dermatol 2015; 8:
19–25.
35 Wollina U. Midfacial rejuvenation by hyaluronic acid fil-
lers and subcutaneous adipose tissue - A new concept.
Med Hypotheses 2015; 84: 327–30.
36 Taub AF. Cheek augmentation improves feelings of facial
attractiveness. J Drugs Dermatol 2012; 11: 1077–80.
37 Wollina U. Improvement of tear trough by monophasic
hyaluronic Acid and calcium hydroxylapatite. J Clin
Aesthet Dermatol 2014; 7: 38–43.
38 Hirmand H. Anatomy and nonsurgical correction of the
tear trough deformity. Plast Reconstr Surg 2010; 125:
699–708.
39 Pessa JE, Garza JR. The malar septum: the anatomic basis
of malar mounds and malar edema. Aesthetic Surg J
1997; 17: 11–7.
40 Funt DK. Avoiding malar edema during midface/cheek
augmentation with dermal fillers. J Clin Aesthet Dermatol
2011; 4: 32–6.
41 Raspaldo H, Gassia V, Niforos FR et al. Global, 3-dimen-
sional approach to natural rejuvenation: part 1 - recom-
mendations for volume restoration and the periocular
area. J Cosmet Dermatol 2012; 11: 279–89.
42 Sullivan PK, Hoy EA, Mehan V et al. An anatomical eval-
uation and surgical approach to the perioral mound in
88
facial rejuvenation. Plast Reconstr Surg 2010; 126:
1333–40.
43 Wollina U. Perioral rejuvenation: restoration of attractive-
ness in aging females by minimally invasive procedures.
Clin Interv Aging 2013; 8: 1149–55.
44 Macchi V, Tiengo C, Porzionato A et al. Histotopographic
study of the fibroadipose connective cheek system. Cells
Tissues Organs 2010; 191: 47–56.
45 Sandoval SE, Cox JA, Koshy JC et al. Facial fat compart-
ments: a guide to filler placement. Semin Plast Surg 2009;
23: 283–7.
46 Lee SH, Gil YC, Choi YJ et al. Topographic anatomy of
the superior labial artery for dermal filler injection. Plast
Reconstr Surg 2015; 135: 445–50.
47 Reece EM, Rohrich RJ. The aesthetic jaw line: manage-
ment of the aging jowl. Aesthet Surg J 2008; 28: 668–74.
48 Rohrich RJ, Pessa JE, Ristow B. The youthful cheek and
the deep medial fat compartment. Plast Reconstr Surg
2008; 121: 2107–12.
49 Beer K, Beer J. Overview of facial aging. Facial Plast Surg
2009; 25: 281–4.
50 Rossell-Perry P, Paredes-Leandro P. Anatomic study of
the retaining ligaments of the face and applications for
facial rejuvenation. Aesthetic Plast Surg 2013; 37:
504–12.
© 2015 Wiley Periodicals, Inc.
Copyright of Journal of Cosmetic Dermatology is the property of Wiley-Blackwell and its
content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.