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J Stomatol Oral Maxillofac Surg 000 (2021) 1−8

Available online at

ScienceDirect
www.sciencedirect.com

Features to consider for mimicring tissues in orofacial aesthetics with

optimal balance technology and non-animal stabilized hyaluronic acid
(RestylaneÒ ): The MIMT concept
Victor Rogerioa, Marcelo Germani Vieiraa,f, Viviane Rabeloa, Ana Claudia Carboneb,
Daniel Augusto Machado Filhoc, Adriana Mendonça da Silvad, Giancarlo De la Torre Canalese,*
a
Let's HOF Academy, Sa ~o Paulo, Brazil
b ~o Paulo, Brazil
Private Practice, Sa
c
Pro ~o Paulo, Brazil
spere Facial Institute, Sa
d
Estadual University of Feira de Santana, Brazil
e ~o Paulo, Sa
University of Sa ~o Paulo, Brazil
f
Dental Research Division, School of Dentistry, Ibirapuera University, Sao Paulo, Brazil

A R T I C L E I N F O A B S T R A C T

Article History: Nonsurgical cosmetic treatments have significantly increased over the last decade. Therefore, this study aims
Received 27 July 2021 to review the features that should be considered in orofacial esthetic procedures, thorough of a proposal of a
Accepted 6 September 2021 new concept called the tissue mimicry concept (MIMT concept) and filling techniques. The MIMT concept
Available online xxx
described in this article comprises knowledge about anatomy of the face and associated structures, under-
standing of aging and how this process affects the facial tissues interactions (skin, subcutaneous tissues,
Keywords:
muscles, and bones), interpretation of facial analysis, comprehension of dermal fillers characteristics and dis-
Hyaluronic acid
cernment of the correct filling technique for each region. Based on these variables the MIMT concept pro-
Dermal fillers
Anatomy
poses the implantation of the minimum-effective quantity of acid hyaluronic fillers (HA) with different
Rheology physical, chemical and rheological properties (complex viscosity and elastic modulus) in the correct layers;
Cell aging in order to optimize their performance resulting in a natural appearance with fewer risks of adverse events.
Rejuvenation the versatility, acceptable safety profile, biocompatibility and greater patient compliance presented in the
RestylaneÒ line (by Galderma) should be taken in consideration, since the use of a proper HA is noteworthi-
ness. The Non-Animal Stabilized Hyaluronic Acid Tecnology (NASHAÒ ) and the Optimal Balance Technology
(OBTÒ ), which make up this line of fillers, allow us to have very firm to very flexible gels, with different parti-
cle sizes, with an optimal concentration of HA and with viscoelastic and biocompatible characteristics
according to the region of the treated face.
© 2021 Elsevier Masson SAS. All rights reserved.

1. Introduction
Nonsurgical cosmetic treatments such as temporary, semiperma-
nent, and permanent cosmetic injectables, have significantly
increased in popularity over the last decade in different fields, span-
ning from dermatology and plastic surgery to dentistry. In addition,
minimally invasive cosmetic procedures have increased by 144%
since 2000. According to the International Society of Esthetic Plastic
Surgery [1], procedures on the face and head increased in 13.5%, non-
surgical injectables were the most popular treatments with 8.6% of
increase and although botulinum toxin remained the most used, hya-
luronic acid (HA) continued to grow with an increase of 15.7%
* Correspondence to: Department of Prosthodontics, Bauru School of Dentistry, Uni-
versity of S~ vio Pinheiro Brisola, 9-75,.CEP 17012-901 Bauru, SP, Brazil.
ao Paulo, Al. Octa
E-mail address: giancarlodelatorrec@gmail.com (D.l.T. Canales).
compared to 2018. In addition, these data shows [1] that soft-tissue
fillers injection are the second most frequent minimally invasive pro-
cedure performed in the USA and in Brazil. It can be expected that an
evolution in surgical practices will result from injectables using [2].
Therefore, HA fillers have become the top injected soft filler agent
around the world.
HA is a natural glycosaminoglycan composed of glucuronic acid
and N-acetyl glucosamine disaccharide units which is easy to use,
long-lasting, biocompatible, nonallergenic, noncarcinogenic, nonmi-
gratory, inexpensive; can be transported and stored in room temper-
ature; has a long shelf life and reproducible results; and is FDA
approved, features that should be considered for an ideal soft tissue
filler [3]. Its early applications were quite diverse, including joint
synovial fluid replacement to treat osteoarthritis and in ophthalmo-
logic surgery for vitreous replacement [4]. In the aesthetics field, the
first HA cosmetic injectable was not approved by the FDA in the

https://doi.org/10.1016/j.jormas.2021.09.004
2468-7855/© 2021 Elsevier Masson SAS. All rights reserved.

Please cite this article as: V. Rogerio, M. Germani Vieira, V. Rabelo et al., Features to consider for mimicring tissues in orofacial aesthetics with
optimal balance technology and non-animal stabilized hyaluronic acid (RestylaneÒ ): The MIMT concept, Journal of Stomatology oral and
Maxillofacial Surgery (2021), https://doi.org/10.1016/j.jormas.2021.09.004
JID: JORMAS
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V. Rogerio, M. Germani Vieira, V. Rabelo et al.
United States until 2003 with the approval of RestylaneÒ [5], even
though plenty of studies had already demonstrated a decreased of
HA in skin with aging, showing the necessity to replenish the HA lost
in this process in order to restore skin and facial characteristics [6].
Since the introduction of RestylaneÒ , various other forms of HA have
been approved by the FDA for cosmetic use [7]. Therefore, knowing
the physical and chemical characteristics of each HA form as well as
its compatibility with tissues is of main importance for clinical practi-
tioners.
In the same way, the anatomy of the human face has received
intensive attention during the last decade, as a result of the increase
of facial rejuvenation procedures [8,9]. Facial aging is the result of the
interplay of changes occurring in both the soft-tissue envelope
(muscles, ligaments, adipose tissue, and skin), underlying facial skele-
ton [8,10], and teeth [11]. However, no sufficient information is
known about the relative contribution of each, which includes varia-
tions in different regions of the face and among individuals.
Notwithstanding that aging of the skin surface is manly influ-
enced from environmental factors, internal soft-tissue laxity, and tis-
sue ptosis certainly alter the skin tone and texture [12]. In this
manner, a high number of treatment options based on the underlying
facial anatomy of each region, in which HA stands out; are available
for managing volume loss in the aging face, minimizing aging, and
restoring face youthful appearance [13]. Thus, a complete under-
standing of the three-dimensional composition and layered concept
of facial anatomy, as well as a full and comprehensive esthetic
evaluation of the patient and the understanding of the patient’s
goals are of main importance in any treatment plan with soft tissue
fillers [14,15].
This article is not on the various techniques of filler injecting but is
about a new concept proposal called the tissue mimicry concept
(MIMT concept), which contemplates the anatomical basis, which is
the foundation for logical use of injectables, considering the impor-
tance of a better understanding of soft tissue fillers differences in
composition, properties, their associated tissue reactions and the
knowledge of the anatomic characteristics of the face. Therefore, the
present report aims to review the features that should be considered
in orofacial esthetic procedures, thorough of a proposal of a new con-
cept called: the tissue mimicry concept (MIMT concept), which
embraces knowledge of the anatomy and aging of the face, HA bio-
mechanics and biochemistry, and filling techniques that will serve as
guidelines to the clinical practitioners in order to obtain optimal out-
comes in patients requiring aesthetics procedures with HA.
2. Review
2.1. Aging physiology
The soft tissues of the face are basically organized into five differ-
ent layers, which are (1) skin, (2) subcutaneous layer, (3) musculoa-
poneurotic, (4) subaponeurotic, containing ligaments and soft- tissue
spaces, and (5) deep fascia. However, there are areas with more and
less layers, such as the temporal region, where ten layers [16] were
identified, and the infraorbital region with three layers [17]. These
layers are interconnected and secured to the facial skeleton by the
retaining ligaments perpendicular to the layers, which connect all
layers to the deep fascia (periosteum on the facial skeleton). Aging
changes are seen in both skeleton and layers of the facial soft tissue,
in which a thinning of the superficial layers and a weakening of the
retinacula cutis structure in the subcutaneous tissue with fat pad
atrophy occurs [8]. The face’s decrease volume results in a reduction
of tissue tone and laxity of the retaining ligaments [8].
Additionally in the aging process, the stomatognathic system also
undergoes changes as the individual ages. The bone remodeling
occurs inexorably, regardless of the presence or absence of dentition
[11]. In individuals who have relatively intact dentition, the alveolar
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bone remodeling tends to keep the total facial height more stable
during adulthood [18]. When the elderly has tooth loss, or edentu-
lism, bone remodeling will be more significant because the absence
of teeth accelerates the resorption of the alveolar bone in the region
[11]. This is because when an individual loses teeth, the demand for
bone support around the missing teeth decreases, leading to bone
resorption in non-active areas [19].
Aesthetically apparent results of the aging process include wrin-
kles, greater visibility of bony landmarks, transverse forehead lines
become prominent and can be accompanied by lowering of the eye-
brows, increased prominence of the nasolabial folds, vertical rhytides
in the perioral area, ptosis of the oral commissures, thinning of the
lips, flattening of the upper lip with less definition of the Cupid’s
bow, a development of a labiomandibular groove and a prejowl
depression (marionette lines) [ 6,14]. These aesthetics consequences,
demonstrates that face aging results from changes in all layers of the
soft tissues and the underlying facial skeleton. Although it is well
known that all layers are interrelated, the contribution of each one of
them in the different regions of the face and between individuals
have not been reported [15]. In fact, orofacial tissues like teeth and
gum [20] must also be evaluated, in order to achieve harmonious
results with natural aspects in both intra and extra orofacial tissues.
Specific alterations occur in the aging process of each layer. In the
superficial dermis, the elastic apparatus almost completely loses its
verticals disposition in the senile skin causing a decrease in density
of collagen fibers and a progressive flattening of the epidermo-der-
mal junction; processes that are associated with a reduction of hya-
luronic acid [21]. The fat compartments of the subcutaneous and
subaponeurotic tissues lose adhesions and volume, which causes
migration and redistribution of fat pads throughout life and a
decrease of the support for the other layers [15]. The mimic muscles
and muscle fascia located in the superficial aponeurotic muscle sys-
tem lengthen with age, increase muscle tone, and have shorter ampli-
tude of movement alterations that induce tightening of the muscles
of the face, limit the amplitude of facial expression, produce perma-
nent contractures which result in shifting of fat and permanent skin
wrinkling [13]. Finally, the facial bones covered by the periosteum
also changes throughout life affecting the appearance and facial
expressions. In the maxilla, resorption occurs mainly in the region of
the piriform fossa and malar eminence. In the mandible, the most
susceptible areas to resorption are in the transition from chin to man-
dible (pre-jowl) and in the goniac angle and in the orbit, the resorp-
tion of the projection of the supraciliary arch is the most prevalent
[10] (Fig. 1,Figure 1).
2.2. Facial analysis
The concepts for performing a dental or facial treatment, currently
converge a complete analysis of all facial contours and measures,
which must necessarily interact naturally with bone and dental
parameters [22]. This synergy between both analyzes, has been over-
looked for years, and often led to an esthetic mismatch which have
been influenced by the lack of perception about facial aesthetics by
dentists together with the no consideration of dental function and
aesthetics in facial treatments by plastic surgeons and dermatologist
[23]. Although cephalometric analysis which is a valuable tool in den-
tistry for facial assessment is also considered an important determi-
nant for treatment planning in aesthetics, today the focus is primarily
on soft tissue assessment with the goal of achieving the skeletal and
dental changes necessary to achieve both functional and esthetic
enhancement [24].
Pre-selected esthetic standards may not be ideal for treating all
patients, but they can be considered a starting point in orofacial pro-
cedures. No mathematical rule can guide facial treatments
completely; therefore, the subjective sense of what is visually attrac-
tive belongs to the professional and should be apply according to the
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V. Rogerio, M. Germani Vieira, V. Rabelo et al.
Fig. 1. (B) Increased goniac angle due to decreased bone structure due to aging. (A) Changes in soft and hard tissues, decreased bone support and migration of caudal blood from soft
tissues. (C) Redistribution of superficial fat pads resulting from aging. (D) Aging of the hard tissues causing the decreased bone support of the face.
patients’ needs [25]. Notwithstanding, the type of face will provide
information about which procedure should be performed to improve
structurally and progressively facial contours [26]. Also, the diagnosis
and treatment planning of facial aesthetics into three major areas
could be used as a framework to guide the evaluation of the esthetic
needs of each particular patient, focusing on the clinical examination
of the patient in rest and smile animation and in physical dimensions
[27]. These three components were divided into macro-aesthetics,
mini-aesthetics, and micro-esthetic. The macro-aesthetics encom-
passes the face in the three planes of the space assessing the profile,
vertical proportions, lip fullness, chin-nasal projection, and facial
widths. The mini-aesthetics focuses on the smile framework evaluat-
ing the incisor display, transverse smile, smile symmetry, crowding
and smile arc, and the micro-esthetic includes gingival shape and
contour, black triangular holes tooth shade and proportion in height
and width, and other dental characteristics [27]. Therefore, facial
optimization must preserve as many positive elements as possible
and consider a full analysis of all intra and extraoral tissues, while
harmonizing those elements that do not satisfy the esthetic and func-
tional needs of the patient [27].
2.3. Dermal fillers features
The search for esthetic solutions in order to improve the contour,
structure and volume of the face has been reported since 1893 with
the use of autologous fat, and included, Polytetrafluoroethylene, Poly-
methylmethacrylate, and HA [28]. HA is a non-sulfated glycosamino-
glycan that is composed of repeating polymeric disaccharides of D-
glucuronic acid and N-acetyl-D-glucosamine linked via glycoside
bond in the arrangement of alternating b- (1!4) and b-(1!3) bonds
[7]. This biomolecule has commonly been used to inject into the der-
mis (as dermal filler) to restore skin volume and minimize the
appearance of wrinkles as well as nasolabial folds. They are specifi-
cally injected into skin folds, deep wrinkles to lift and reshape the
face due to its unique characteristics that mimic the natural materials
found in cells [29].
RestylaneÒ which is an HA from the NASHAÒ line of Galderma
industry was the first HA filler approved in 2003 by the Food and
Drug Administration (FDA). In addition, Galderma fillers are classified
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into two technologies, OBTÒ and NASHAÒ , which were developed
with physical, chemical, and rheological properties specifically
adapted for each indication. Even though the concentration of HA
(20 mg/ml) is the same in all presentations; the technologies, degree
of cross-linking, and calibration varies, resulting in fillers with differ-
ent firmness, volumizing and projection capacity [14,28].
Gels with OBTÒ technology, formerly EmervelÒ , are mainly volu-
mizers that have high flexibility, they were developed for contour
and natural expression in dynamic areas of the face. OBTÒ gels pres-
ent soft and diffuse tissue integration, they are indicated for mobile
areas and to mimic superficial fat pads [30]. They have a concentra-
tion of 20 mg / ml of hyaluronic acid, have different degrees of cross-
linking and three particle sizes which results in gels with different
textures and different projection capacities (Graphic 1 and Chart 1)
[31]. Its comercial presentations are Restylane FynesseÒ , Restylane
RefyneÒ with lidocain, Restylane Kysse with LidocainÒ , Restylane
Defyne with LidocainÒ and Restylane Volyme with LidocainÒ . In addi-
tion, Restylane FynesseÒ , Restylane RefyneÒ and Restylane KysseÒ .
They are indicated for dynamic areas that must have their natural
expressions preserved, because their particles are smaller, their
crosslinking is low to medium and are more flexible with low to
moderate volumizing capacity [32]. For less dynamic areas, where we
want to defined contours and higher volumes, Restylane VolymeÒ
and Restylane DefyneÒ , are indicated since they present bigger and
more reticulated particles [31] (Graphic 1 and Chart 1).
On the other hand, in NASHAÒ , gels were developed for projection
and precision, which make them ideal for mimicking bone tissue and
firm adipose cushions, with precise and focal integration of the prod-
uct to the tissue [14]. NASHAÒ gels are manufactured with hyaluronic
acid technology stabilized with homogeneous particles [35] (Figure 2)
and natural bonds that incorporate only 1% cross-linking, resulting in
a gel with a high degree of purity [33]. They are indicated for less
dynamic and deeper areas Its commercial presentations are Restylane
LyftÒ , Restylane Lyft with LidocainÒ , RestylaneÒ , Restylane with
LidocainÒ , Restylane VitalÒ and Restylane Vital LightÒ [31,34]. Almost
all gels of NASHAÒ have the same concentration of 20 mg / ml of HA
except for the Restylane Skinboosters Vital LightÒ which contains of
12 mg / ml of HA [14,35,36]. The particle size differs between prod-
ucts. Restylane LyftÒ contains bigger particles, has greater resistance
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V. Rogerio, M. Germani Vieira, V. Rabelo et al.
Fig. 2. Scanning electron microscopy featuring of NASHAÒ particle homogeneity.
to deformation, more firmness and greater projection capacity;
whereas RestylaneÒ has smaller particles and consequently a lower
projection capacity although no significant differences were found.
The Skinboosters Restylane VitalÒ and Restylane Vital LightÒ are
two formulations based on NASHAÒ gel with microparticles that cap-
ture water from the skin and act as a water reservoir [37,38]. How-
ever, since they are NASHAÒ gels, although microparticulate they are
able to promote an optimal definition of lip contour [31,37]. Its appli-
cation plan is in the superficial subcutaneous tissue [38]. The applica-
tion is well tolerated, and improve the quality, structure, elasticity,
and reduced skin surface roughness [38]. Its main indications are for
fine wrinkles, periorbital, peri-orbicular region, and lips [31,38].
RestylaneÒ has a high safety profile that can be associated with
the purity of the gels [33] and the homogeneity of the particles that
provides better tolerability and less inflammatory response [39]. Clin-
ical results showed a 0.02% of adverse events for the NASHAÒ line in
more than 40 million treatments worldwide [40]. In the same way,
the OBTÒ line did not present late adverse events in a study with
1700 patients evaluated over 15 months [41]. In addition to these
data, RestylaneÒ showed the best reversibility in a degradation study
in response to hyaluronidase [42]. Even though the use of
Fig. 3. Scheme of cannula angulation considered safe by Tansatit et al., 2016[51].
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hyaluronidase is off label, it is still the unique substance known as
capable of completely degrading hyaluronic acid and reversing a seri-
ous vascular adverse event or an esthetic over correction [43−45].
2.4. Filling techniques
Injection procedures with HA includes lifting, augmentation,
correction of asymmetry, modification of the shape, softening of
folds and wrinkles, and rejuvenation. Soft tissue filler injections
are performed using either sharp tip needles or blunt tip cannulas
[46]. The injector’s preference of the products and devices to per-
form these procedures varies based on injection style and personal
design, although the majority of injectors prefer to use a cannula
rather than a needle [47]. Previous studies [48] have shown that
injecting with a needle perpendicular to the bony surface distrib-
utes the filler material into all fascial planes, whereas injecting
with a cannula parallel to the bone surface positions product solely
in the targeted plane (Chart 2). These studies concluded that
injecting with a sharp-tip needle conferred a greater risk of prod-
uct placement into unintended fascial layers vs cannulas, since
needle injections potentially lead to accidental intra-arterial
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V. Rogerio, M. Germani Vieira, V. Rabelo et al. Journal of Stomatology oral and Maxillofacial Surgery 00 (2021) 1−8

application [48]. Notwithstanding, using a canula could be consid-
ered more secure than using a needle, absolute safety cannot be
guaranteed in cannula injections even in experienced injectors,
since it depends on the size of the cannula (larger cannulas are
recommended) [49] (Figure 3). Also, it is important to consider the
facial arterial vasculature due to its high positional variability
between individuals and between both sides of the same individ-
ual [50].
In the same way, it is important to consider the correct type of HA
according to the region and plane in which it will be injected. There-

Graphic 1. Bars representing modulus of elasticity (G') that demonstrate the ability to resist deformation and its association with the firmness of the gel. Dotted line representing
Swelling Factor (SwF) that demonstrate the water's absorption capacity of the gel and its association with the flexibility of the gel.Font: Edsman KML et al., 2018[33]; Fagien S et al.,
2019[34] (adapted)

Chart 1. Features of Restylane Hyaluronic Acid types.

5
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V. Rogerio, M. Germani Vieira, V. Rabelo et al. Journal of Stomatology oral and Maxillofacial Surgery 00 (2021) 1−8

Chart 2. Filling techniques protocols for Hyaluronic Acid procedures.

fore, the MIMT concept proposes a guide in which all these variables
are considered in order to help injectors in the decision process of
which HA should be used for each indication [34]. Therefore, for
mimicking bone tissue it should be chosen a gel with high G’ and
6
large size of particle, on the other hand for subcutaneous tissue better
cohesively with G’ from low to moderate and medium to small parti-
cle size is recommended. For fixed regions in a shallow or deep plane,
products with high G’ with medium and large particles and with
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V. Rogerio, M. Germani Vieira, V. Rabelo et al.
moderate to low swelling factor should be used. For mobile regions in
a deep plane, products with high G’ with medium and large particles
and with moderate to low swelling factor must be considered. On the
other hand, for mobile regions in a flat surface, products with low to
moderate G’, with small to medium particles and with moderate to
low swelling factor could be used. Regarding tear trough, in which
only three layers can be found, and natural water retention and diffi-
cult lymphatic drainage is present, products with moderate to high
G’ with small particles and low swelling factor are the most indicated.
Finally, for lip’s mucosa which presents a high mobility, in a superfi-
cial flat, products with low to moderate G’ with small particles, mod-
erate swelling factor should be considered.
The protocols of filling techniques described below (Chart 2 ) aim to
guide the restoration of the tissues that have undergone through
changes during aging, considering the area and layer of injection, type
and quantity of product and the device used for each indication [51,52].
3. Conclusion
Thus, it can be concluded that the use of the MIMT concept could
help injectors to restore volume and support of the structures in a
gradual and safe manner considering a complete analysis of the
patient and proper HA characteristics for each treatment. Due to the
physical, chemical, and rheological characteristics of RestylaneÒ gels,
we recommend them to mimic different layers of the tissues and to
restore facial shapes and contours of the face through all the aging
process of patients of both sexes.
Acknowledgments
To GALDERMAÒ , for the language editing assistance of the manu-
~o Paulo Research Foundation - FAPESP for the post-
script. To the Sa
doctoral scholarship of Giancarlo De la Torre Canales (grant 2017/
21674-0) and the Bahia States Aid Research Foundation (FAPESP), for
the doctoral scholarship of Adriana Mendonça da Silva[1−52]. To Mr.
Rui Santos (Santos pub agency) for the support in the figure’s elabora-
tions. The authors did not receive compensation for writing the man-
uscript.
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