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Hyaluronic Acid Fillers
Science and Clinical Uses
Karol A. Gutowski, MD*
Facial aging may manifest as skin texture and
color changes, formation of fine lines and deeper
creases, more pronounced active wrinkles, and
overall facial soft tissue decent. Decreased skin
tone, fat loss, and underlying bony changes
contribute to the loss of facialfullness. Each of these
components of facial aging can be addressed by
specific treatments such as medical grade skin
care and resurfacing, neuromodulators, and
soft tissue fillers. Althoughnot a substitute for surgi-
cal rejuvenation, nonsurgical options are more
accepted by patients owing to convenience, lower
initial cost, less downtime, and fears of “going under
the knife.” In this environment, hyaluronic acid (HA)
fillers have become in leading tool in not only
maintaining a youthful facial appearance, but also
for enhancing facial features in younger patients.
Although HA fillers may seem to be similar, they
actually each have different physical properties
that differentiate them, making proper product
choice important when used for facial rejuvena-
tion. Factors such as HA concentration, amount
of cross-linking, particle size, extrusion force,
and elastic modulus (G0) influence product selec-
tion and indications. Therefore, there is no univer-
sal HA filler. Although there is some overlap in their
clinical uses, they should not be considered inter-
changeable in all situations.
This section highlights of a more detailed anal-
ysis of HA fillers by Kabik and colleagues.
HA is
found in human tissue but the injectable products
are obtained from animal or bacterial sources. The
HA molecule itself is a glycosaminoglycan disac-
charide composed of alternately repeating units
of D-glucuronic acid and N-acetyl-D-glucosamine.
At physiologic pH, HA binds water extensively,
providing “fullness” in the tissue. HA may be modi-
fied by chemical cross-linking between HA
strands, which increases product firmness, mak-
ing it more resistant to stress, and also making it
more resistant to in vivo enzymatic degradation
resulting in a longer duration of filler effect.
Although each product has a listed HA filler
concentration, there may be variation in the
amount of soluble versus insoluble HA. Because
the soluble HA is metabolized rapidly, it does not
contribute to clinical effectiveness. Therefore,
listed HA concentrations may not truly reflect
product performance.
Conflicts of Interest: None.
Disclosures: The author is an instructor for Bellafill (Suneva Medical), a non-hyaluronic based fillers mentioned
in this article.
Division of Plastic Surgery, University of Illinois, Chicago, IL 60611, USA
* 820 South Wood Street, Suite 515 CSN, Chicago, IL 60612-7316.
E-mail address:
Hyaluronic acid Soft tissue fillers Juvederm Restylane Voluma Belotero
Hyaluronic acid (HA) injections are an integral part of facial aesthetics.
HA products are similar but not interchangeable.
Individual patient assessment and an understanding of facial aging is necessary for optimal results
with HA injections.
Clin Plastic Surg 43 (2016) 489–496
0094-1298/16/$ – see front matter Ó2016 Elsevier Inc. All rights reserved.
The rheology of HA fillers is complex and labora-
tory measurement differences may not translate to
clinical differences. However, a products’ G0may
be used to describe its firmness or ability to “lift”
tissue. A high G0product will require more applied
stress to deform it, whereas a low G0product will
deform with little applied stress.
In clinical terms, low G0HA products may be bet-
ter for fine lines and wrinkles and where firmness is
not desired, for example in the lips. High G0prod-
ucts may be better suited for deeper tissue eleva-
tion such as moderate to severe nasolabial folds
and malar enhancement. Reported G0measure-
ments in Pascal units are listed in ascending order
Finally, because HAs bind water, they may result
in tissue swelling after injection. This is partially
dependent on HA molecule modifications and
the amount of cross-linking.
Proper patient assessment includes not only the
area of their present concern, but an overall facial
assessment and plans for future treatments. In
middle-aged and older patients, HAs typically are
combined with neuromodulators and medical
grade skin treatments to achieve proper facial
rejuvenation. Despite patient hopes, not all facial
aging can be improved with fillers. A discussion
of why more invasive treatments are appropriate
may be needed. Likewise, expectations that 1 or
2 syringes of a product will give dramatic results
will also need to be addressed. Lip enhancements
may only need 1 or 2 mL of an HA, but moderate
facial aging may require 1 to 2 mL in each temple,
malar region, nasolabial fold, and perioral area.
Eight to 10 mL of HA (or more) may be used in
some patients to achieve a “liquid facelift.” If
high filler volumes are being considered, other
longer acting products such as L-poly-lactic acid
(Sculptra) and polymethyl methacrylate (Bellafill)
should be discussed. Calcium hydroxylapatite
(Radiesse) is another option for deeper injections
to achieve tissue elevation, such as in the malar
or temple regions.
A written informed consent should be obtained
before the first injection session. Standard photo
documentation of the area being treated and the
entire face should be done before any treatment.
Because many of the changes from filler injections
are subtle, consistent before and after images are
important in measuring outcomes and educating
Not all ethnic groups have similar needs and this
should be taken into account. For example,
whereas Caucasian patients may seek injections
to address age-related changes, Asian patients
may be younger and be seeking changes in facial
shape. The “T zone” (forehead, nose, cheeks, and
chin) can be projected in such cases to reshape
the face.
Ethnic groups with darker skin types,
such as African Americans,
may have fewer fine
lines and wrinkles and will focus more on volume
loss. Latino patients may have unique cultural con-
siderations that can influence treatment.
Men are
more likely to focus on regaining stronger male
features, such as in the chin, and also present for
nasolabial fold and tear trough correction.
Depending on the injection site and size of needle
used, analgesic modalities include topical anes-
thetics, ice packs, distraction techniques, local
anesthetic injections, and nerve blocks. Some
HA products are available with lidocaine mixed in
the syringe, which decreases injection discomfort.
The injection site should be cleaned in a wide
area with appropriate skin disinfectant. Dry
iodine-based solutions can be wiped off with an
alcohol pad to allow assessment of skin color for
signs of blanching or intravascular injection. Tech-
nique should be as aseptic as possible because
late infections and biofilm formation can occur.
For intradermal injections, short 29-G needles
work well. When using a more viscous HA product,
30-G and 31-G needles can be used. For subder-
mal injections, longer 27-G or 29-G needles are
useful. More recently, disposable blunt-tipped in-
jection cannulas have been favored for subdermal
and deeper injections because they may cause
less bruising and are less likely to result in an intra-
vascular injection.
Specific injection technique depends on the in-
jection site, tissue plane, and clinical problem be-
ing treated. Small bolus injections (0.05–0.1 mL)
are appropriate for deep and supraperiosteal in-
jections such as for malar elevation or filling in
the prejowl sulcus. Fine lines and wrinkles are
best treated with smaller volume linear injections
of product into the dermis, parallel to the line being
injected. Elevation of more superficial tissue, such
Belotero Balance 128
Juvederm Ultra XC 207
Juvederm Ultra Plus XC 263
Voluma 398
Restylane-L 864
Restylane Lift-L 977
as the lip corners or cheek hollows, can be done
with a cross-hatching technique of linear perpen-
dicular injections. A fanning technique from a sin-
gle injection point is useful to highlight or elevate
an area. Low injection pressure and small volume
injections will prevent overcorrection. If tissue
swelling makes it difficult to assess the results,
the injection can be stopped and repeated in 1 to
2 weeks.
After the injection, the area should be palpated
to check for any lumps or unevenness, which
can me massaged until smooth. Cool gel packs
are useful immediately after injection to reduce
swelling and bruising. Patients can resume regular
activities, but should be instructed not to massage
or otherwise manipulate the treatment area.
Follow-up evaluation is suggested at 2 weeks to
determine if additional injections are needed. If any
nodules are seen, they may still be able to be
manipulated and made smooth. If an area is obvi-
ously overcorrected, or the patient is not satisfied
with the results, HA fillers (unlike non-HA fillers)
can be reversed with hyaluronidase. A human re-
combinant hyaluronidase (Hylenex, Halozyme
Therapeutics) is preferable to animal derived hyal-
uronidase. Small amounts of HA may be dissolved
with 15 to 30 units of hyaluronidase, although more
may be needed (50–100 units) for larger amounts
or in products with high HA cross-linking.
HA products are not intended to be stored for
use after opening the syringe. However, if used un-
der sterile conditions, they may be stored for at
least 2 months without any bacterial growth.
Worldwide, there are many HA injectable products
with indications for both facial aesthetic and other
uses. The products mentioned below will be
limited only to HA fillers approved by the US
Food and Drug Administration (FDA) for facial aes-
thetics as of January 2016.
Juvederm Ultra, Juvederm Ultra Plus, and
The Juvederm and Voluma groups of products are
made by Allergan Inc. (Irvine, CA).
Juvederm Ultra has the lowest G0(207 Pa) and
Juvederm Ultra Plus has a slightly higher G0
(263 Pa). Both are made with proprietary Hyla-
cross technology, which allows high water uptake
by the HA gel after injection. This may cause more
“swelling” and the appearance of overcorrection.
Voluma has the highest G0in the Allergan HA prod-
uct group (398 Pa) and is approved for malar
augmentation. Volift (G0340 Pa) and Volbella (G0
271) are similar to Voluma, but are not currently
FDA approved. These last 3 products use proprie-
tary Vycross technology and absorb less water
than Juvederm Ultra or Juvederm Ultra Plus.
Restylane, Restylane Silk, and Restylane Lyft
The Restylane group of products is made by Gal-
derma (Uppsala, Sweden) and each product also
has specific properties. Restylane Silk is a low G0
small particle HA that is FDA approved for lip
augmentation and treatment of perioral lines. It is
also useful for fine lines in other areas, tear
troughs, and in places where less filler “lift” is
Restylane has a high G0(864 Pa),
whereas Restylane Lyft (formerly called Perlane)
has the highest G0(977 Pa) of the FDA-approved
HA products.
Belotero Balance
Belotero Balance is approved for mid to deep
dermal injections for correction of moderate to se-
vere facial wrinkles and folds and is considered a
superficial to midlevel volumizer. It has a low G0
(128 Pa), which makes it appropriate for treating
fine lines and wrinkles.
Other Belotero products
not yet FDA approved include Belotero Volume
(a deep volumizer), Belotero Intense (a midlevel
volumizer), and Belotero Soft (a superficial
Unlike Voluma, Juvederm, and Retylane prod-
ucts, Belotero Balance available in the United
States does not contain lidocaine for injection
comfort. However, it may be mixed with 0.15 mL
of 1% lidocaine per 1 mL of product for a more
comfortable injection. The formulation of Belotero
may produce less Tyndall effect (a visible bluish
discoloration of the HA when injected in the super-
ficial dermis), making it useful for fine lines, areas
of thin skin, and superficial injections.
Studies to determine the duration of clinical
improvement after HA injections frequently use
standardized assessment scales with patient and
physician reported scores. A 1- or 2-point
improvement on a 5-point scale is considered
effective. These same studies may allow for touch
up injections and corrections during the study
phase. For Juvederm products, Restylane prod-
ucts, and Belotero Balance, duration is frequently
at least 6 months, with some patients seeing re-
sults up to 1 year. Voluma has a reported duration
of 1 to 2 years.
Clinical experience shows that there is wider
variability in the time needed before retreatment.
Hyaluronic Acid Fillers 491
This may be based on injection technique, injec-
tion site, and individual patient HA metabolism or
just owing to initial treatment undercorrection,
which becomes evident after swelling resolves.
Therefore, patients should be advised that, in
some cases, the duration of results may be shorter
than expected and retreatment, or a different
product, may be needed.
Each patient will have unique goals and expecta-
tions as well as underlying anatomic variability
and stages of aging that need to be considered
when planning treatment. A full facial analysis by
the injector, combined with patient education
and agreement with the treatment plan, will help
to achieve a favorable outcome. In many cases,
a neuromodulator may be used to prevent lines
and wrinkles that form with movement (active
lines) and HAs can be used for lines that are pre-
sent at rest (static lines).
The following facial re-
gions can be improved with HA fillers; most of
these are not FDA-approved indications and
should be considered “off-label” uses.
Forehead Lines
Mild to moderate static lines in the forehead
should first be addressed with a neuromodulator
injection to the frontalis muscle to treat the under-
lying cause. In most cases, these line will improve
after a few months. If needed, deep dermal low to
moderate G0HA injections can be used to fill in any
residual static lines.
Temple hollowness is a sign of aging usually not
noticed by patients and needs to be brought to
their attention. Once addressed, the results can
be dramatic.
Deep injection in the supraperios-
teal plane, starting from the depression superior
lateral to the orbital rim and tapering to the hairline
with a high G0HA can lift and revolumize the
Superior Orbital Rim
Although not a common injection area, the supe-
rior orbital rim can be enhanced for a more mascu-
line appearance, or to provide the appearance of
slight brow elevation by using a high G0HA in the
subdermal or supraperiosteal plane.
Vertical glabellar lines, sometime called the “11’s”
are a common initial complaint of patients seeking
facial enhancement. As with forehead lines, the
first step is to treat the underlying corrugator mus-
cle contractions with a neuromodulator. Then, if
need after a few months, a low to moderate G0
HA intradermal or subdermal injection can be
used to fill in residual static lines. Care should be
taken because this area may be more prone to
filler-associated skin necrosis.
Crow’s Feet
As in the forehead and glabella, active lines are
first treated with neuromodulator injections to the
orbicularis oculi muscle. Although rarely needed,
low to moderate G0HA intradermal injections can
be used for static lines.
Upper Eyelid
Upper orbital hollowness, including sequelae of fat
pad removal, has been improved with HA injec-
This should be done very carefully and
only by experienced injectors who are familiar
with the anatomy in this region.
Tear Troughs and Lower Eyelid Bags
For patients with tear troughs and mild to moder-
ate lower orbital fat pads, a moderate G0HA injec-
tion in the supraperiosteal plane can fill in the
trough (Fig. 1) and make the lower lid fullness
less noticeable.
This area is less forgiving than
other facial regions, because the thin skin may
make the HA product more visible and palpable.
Therefore, undercorrection followed with a touch
up 2 weeks later if needed is a reasonable
approach. Prolonged swelling and late edema
are also common and HA products have lasted
up to 5 years in this facial zone.
In some moder-
ate cases, and most severe cases of lower orbital
fullness, a blepharoplasty is more appropriate.
Deflated earlobes and creases can be improved
with small injections of HA fillers.
High cheek bones are frequently desired by
younger women, and loss of malar volume is com-
mon in older women and men, as well as in pa-
tients with malar hypoplasia. High G0HA fillers
can be injected in the supraperiosteal plane of
the malar prominence and low to moderate G0
HA can be used more superficially for refined
enhancement (Fig. 2). In some cases, adding vol-
ume to the malar area can soften nasolabial folds,
but overfilling should be avoided to prevent an un-
natural appearance when smiling and so as not to
make cheek hollowness more obvious.
Submalar and Cheek Hollowness
Cheek hollowness in the submalar area is
commonly associated with advanced aging,
weight loss, or in very physically active patients
with a low body mass index. Revolumization with
subcutaneous HA fillers can restore a more youth-
ful appearance and improve cheek wrinkles owing
to facial deflation (Fig. 3).
Minor nasal imperfections and deformities can be
improved with HA fillers.
Small dorsal humps
can be “reduced” by adding supraperiosteal vol-
ume above and below the hump to crease a
straight dorsum. Likewise, some dorsal deviations
can be camouflaged with fine supraperiosteal in-
jections on the concave side. Minor tip changes
can be made with careful subcutaneous injections.
Higher G0HA fillers may be better to provide more
structural support as the nasal skin tends to be
tight and can deform low G0products.
Perhaps owing to popular cultural influences, lip
enhancement in younger patients and correction
of lip volume loss in older patients is frequently
requested. Low and moderate G0HA products
are used commonly (Fig. 4). Proper assessment
and aesthetic judgement are critical because over-
done lips are easy to produce. In older patients
with a thin lip and long vertical upper lip, a surgical
lip lift may be a better option. During and after HA
injection, swelling is common and it is wise to limit
injection volumes to 1 mL, then reevaluate and
retreat in 1 to 2 weeks.
Peri Oral, Lip Lines, and Downturned Lip
Vertical upper and lower lip lines should first be
managed with low-dose neuromodulator injec-
tions to control the underlying orbicularis oris mus-
cle contributions. Fine lines can be injected with
low G0prime intradermal injections
and the
downturned lip corners may need higher G0HAs
for improvement. If the depressor anguli oris mus-
cle is contributing to the downturned lip, a neuro-
modulator injection may be added.
Nasolabial Folds
Most early indications and studies were done on
HA injections to improve nasolabial folds. More su-
perficial lines respond well to intradermal injec-
tions of low to moderate G0products. Deeper
folds respond better to higher G0HAs in the subcu-
taneous tissue (Fig. 5).
Fig. 2. Before and after high G0hyaluronic acid injection for malar elevation (Restylane Lyft, 1.5 mL per side).
Fig. 1. Before and after low G0hyaluronic acid injection for tear trough improvement (Juvederm Ultra, 0.5 mL per
Hyaluronic Acid Fillers 493
Marionette Lines
Similar to nasolabial folds, marionette lines
respond well to HA injections (Fig. 6). In the lower
face, conservative amounts should be used
because too much volume may make the lower
face too full and unattractive.
Jaw Line, Prejowl Sulcus, and Chin
The appearance of mild jowls can be minimized by
filling in the sulcus between the jowl and chin with
a supraperiosteal high G0HA injection (Fig 7).
Overcorrection or attempts to improve a larger
jowl may make the jaw look to large and “heavy.”
Posterior to the jowl, and at the mandibular angle,
injections can refine the jawline or give a more
masculine jaw appearance. Likewise, modest
chin augmentation can be achieved with
Although generally considered safe when used by
appropriately trained injectors, there are associ-
ated risks and potentially serious complications.
Mild swelling and bruising can be expected; rarely,
persistent swelling may occur, especially in the
lower orbital area. Palpable lumps, nodules, and
granulomas are not common when proper injec-
tion technique is used. More serious complica-
tions usually involve an intravascular injection,
which can cause significant tissue necrosis and
blindness. A recent FDA warning calls attention
to these events.
All those who inject fillers should know the
specific anatomy of the area they are treating so
as to minimize the risk of intravascular injection.
Suggested techniques for safe injections include:
Avoiding injections in an area with large blood
Use of a blunt cannula instead of a sharp
needle (where appropriate);
Pulling back the syringe plunger before
injection; and
Slow injection with observation for tissue
In the event of an intraarterial injection, which
typically presents with immediate skin blanching
and occasionally pain, immediate treatment is
mandatory. Skin and soft tissue necrosis may
result even if preventative actions are taken.
Fig. 3. Before and after moderate G0hyaluronic acid cheek revolumization (Voluma, 1 mL per side).
Fig. 4. Before and after low G0hyaluronic acid lip enhancement (Juvederm Ultra Plus, 1 mL split between upper
and lower lip).
Fig. 5. Before and after high G0hyaluronic acid injection for nasolabial fold improvement (Restylane, 1 mL per
Fig. 6. Before and after moderate G0hyaluronic acid marionette line correction (Voluma, 0.5 mL per side).
Fig. 7. Before and after high G0hyaluronic acid injection in the prejowl sulcus (Restylane, 0.4 mL per side).
Hyaluronic Acid Fillers 495
Likewise, any vision changes during or immedi-
ately after an injection need to be considered as
an intravascular injection and treated as an emer-
gency. Intravenous injections may present hours
or days later with blue or purple skin discoloration
and tissue slough.
As soon as an intravascular injection is
recognized, a preplanned protocol should be
1. Stop the injection.
2. Inject hyaluronidase under the dermis of the
affected area; 100 units or more may be
3. Administer 1 aspirin orally.
4. Massage the area to break up any residual
5. Apply warm compress.
6. Consider sildenafil (Viagra) for vasodilation.
7. Consider applying nitropaste to affected area.
8. Reassess every 1 hour and inject more
hyaluronidase if needed.
9. Consider hyperbaric oxygen referral if there is
a risk of tissue loss.
10. Antibiotics or steroids are not indicated.
If a vision change occurs, an ophthalmologist
should be notified immediately and a retrobulbar
hyaluronidase injection should be done with
1 hour.
HA fillers have expanded treatment option for
facial aging and are often combined with other
nonsurgical modalities such as neuromodulators
and skin treatments. They are accepted by the
public and should be offered by all plastic
surgeons who perform facial rejuvenation.
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... Early injection laryngoplasty (EIL) with temporary materials is effective for UVFP and may reduce the need for permanent laryngoplasty in specific patient groups [1][2][3]. Since the introduction of distal-chip laryngoscopy, office-based EIL has become favored by UVFP patients [1][2][3][4][5] because it immediately adjusts the vocal position to improve the patients' voice and swallowing functions [3,4,[6][7][8][9]. The feasibility of office-based injection laryngoplasty (IL) and its excellent short-to mid-term voice outcomes have been demonstrated, as a majority of patients are satisfied with the correction of their breathy voice, aspiration, and chronic cough. ...
... Over the years, various materials have been used for EILs, such as Gelfoam, carboxymethylcellulose, calcium hydroxyapatite, autologous fat, and HA. HA is superior to other injectable materials because it has a lower risk of hypersensitivity reactions and is prone to remodeling scars [7,10,11]. Most patients with glottic insufficiency are satisfied with the immediate treatment effect from HA injection. ...
... HA can form a transient polymer network system whenever shear force is applied. HA can be transformed and autonomously reassembled when the force is removed [7,17], a physical property that has made HA an ideal dermal filler for decades. A recent study ...
Background: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified. Methods: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed. Results: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8-27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) (p = 0.026) than in the HHA group (7.5%). Conclusions: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP.
... HA is a natural high molecular weight, belonging to the glycosaminoglycan family, which due to its physicochemical properties is capable to contain up to 1000-fold more water than its own weight [48,49]. HA fillers have been widely used in many aesthetic procedures with good results [46,49,50]. ...
... HA is a natural high molecular weight, belonging to the glycosaminoglycan family, which due to its physicochemical properties is capable to contain up to 1000-fold more water than its own weight [48,49]. HA fillers have been widely used in many aesthetic procedures with good results [46,49,50]. ...
... Different manufacturing related factors, such as HA concentration, polymer chain length, crosslinking degree, or cross-linking technology, impact significantly on different filler properties, such as requisite needle size; particle size; duration; extrusion force; and elastic Modulus (G'), which will critically influence product selection and indication [49][50][51][52][53][54]. ...
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Background Gummy smile (GS) is a nonpathological condition causing esthetic disharmony in which an excessive amount of gingival tissue is exposed when smiling. Nowadays, there is not unanimous agreement regarding both classification and management of GS. This study aimed to present an organized and comprehensive clinical classification of the GS, as well as to discuss a therapeutic approach, with hyaluronic acid dermal fillers.Methods This study is presenting the clinical experience of the authors regarding GS.ResultsThe Mercado-Rosso GS classification has into account aesthetic aspects, etiopathogenetic criteria, and functional aspects of the smile. According to Mercado-Rosso GS-classification-system, GS is divided into 3-types: Type 1, characterized by a lack of support and/or a lack of projection of the upper maxilla; Type 2, due to an imbalance between the strength (excess) and the resistance (defect) of the levator muscles; and Type 3, defined by an excessive strength of the zygomatic muscles, which causes a wide smile and an excessive visualization of the molar teeth.Conclusions The Mercado-Rosso GS classification system is a tool that facilitates the diagnostic and therapeutic approach to the gummy smile. RD Dynamic Restructuring® constitutes a comprehensive therapeutic approach that makes reference to both the effect of the HA filler on the muscle movement and the balance between the muscle strength and the resistance of the soft tissue to be folded in different facial structures). Level of evidence: Level V.
... [2][3][4] HA is a high molecular weight, natural, and linear glycosaminoglycan that is present in all mammals. 5,6 Due to its physicochemical properties, HA is one of the most hygroscopic molecules in nature and hydrated HA can contain up to 1000-fold more water than its own weight. 7 Some specific features of HA influence its properties as a filler, such as polymer chain length, HA concentration, degree of cross-linking, or the cross-linking technology used, which affect its duration, extrusion force, and elastic Modulus (G'). ...
... These phenomena define the distinct products and the indications for which they may be employed. 6,[8][9][10][11][12] One of the most recent generation of fillers was created using the patented Vycross® technology (Allergan, Inc.), which utilizes a proprietary mixture of high and lower molecular weight HA. 13 VYC-25L (Juvéderm Volux®; Allergan plc) represents the latest innovation in the Vycross® range, combining high G' (resistance to deformation) and high cohesivity HA, 14 properties that make it an ideal filler to create and restore facial volume. In clinical practice, VYC-25L has been successfully used to restore and create facial volume in patients with chin retrusion 15,16 and for other esthetic indications. ...
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Background The portfolio of hyaluronic acid (HA) fillers and the techniques of administration have evolved in recent years. The latest innovation in the Vycross® range was the introduction of VYC-25L (Juvéderm Volux®; Allergan plc), a first-in-class filler effective for chin and facial lower third remodeling. The aim here was to provide clinicians who are starting to use VYC-25L with key advice, and to standardize procedures so that optimal and predictable outcomes can be obtained. Methods A multidisciplinary group of experts in esthetic medicine from Spain and Portugal reviewed the properties, treatment paradigms, administration techniques, and potential complications of VYC-25L, on the basis of which they drafted consensus recommendations for its clinical use. Results The consensus panel provided specific recommendations focusing on the patient profile, dose, administration techniques, and the complications of VYC-25L and their management. The panel identified five different profiles of patients who may benefit from VYC-25L, and they drafted recommendations aimed to facilitate the treatment of these patients, namely, microgenia (women/men), masculinization (men), rejuvenation (women/men), facial laxity (women/men), and submental convexity (women/men). In terms of their safety, no specific recommendations were made beyond those established for other HA fillers. Conclusions The evolution of esthetic medicine makes it necessary to update the clinical recommendations that guide patient assessment and treatment with the new HA fillers developed. The current consensus document addresses relevant issues related to the use of VYC-25L on different types of patient, in an attempt to standardize procedures and help specialists obtain predictable results.
... 3,4 Facial volume deficit can be effectively treated using implantation or injection of absorbable or nonabsorbable filler materials of various types. 5,6 Owing to potential complications associated with reversing nonabsorbable fillers, absorbable fillers are preferred. Biodegradable substances in current use are autologous fatty tissue (i.e., subject's own body fat), polylactic acid, calcium hydroxyapatite, and HA. ...
... Before this study, only limited safety data supporting the use of CPM-HA26 in temples and cheeks were available. 5,9,[12][13][14][15][16] Results of the current study support and confirm the safety and effectiveness of CPM-HA26 for the treatment of volume deficiency in temples and cheeks. Treatment was well tolerated by study subjects, with only mild or moderate treatment-related TEAEs reported, and no serious adverse device effects reported during the study, especially no injection-related vascular embolization or delayed inflammatory reactions. ...
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Background: Facial aging is characterized by volume loss and progressive hollowing of temples and cheeks. Biodegradable filler materials are preferred over nonabsorbable materials; of these, hyaluronic acid (HA) fillers are the most often used because of their favorable effectiveness and safety profile. Objective: To confirm the safety and effectiveness of Cohesive Polydensified Matrix (CPM)-HA26 gel in the treatment of volume deficiency. Methods: Subjects received up to 2 treatments in the temples and/or cheeks. A blinded investigator assessed improvement according to the Merz Temple Volume Scale (MTVS) and Merz Cheek Fullness Assessment Scale (MCFAS). Subjects were followed for 48 weeks after the last treatment. Results: In total, 87 healthy subjects were enrolled. The proportion of subjects achieving at least a 1-grade improvement on MTVS and/or MCFAS was above 70% for each (MTVS: Weeks 4, 24, and 48 = 95.4%, 94.2%, and 77.0%; MCFAS: Weeks 4, 24, and 48 = 92.3%, 83.1%, and 71.8%). Based on MTVS and MCFAS scores at Visit 5, improvement remained visible at up to 48 weeks. No treatment-related serious AEs occurred. Conclusion: CPM-HA26 demonstrated both a favorable safety and effectiveness profile, with improvement in facial volume evident for up to 48 weeks. It was well tolerated and had a positive, long-lasting effect.
... It is easily metabolized and supposedly does not have any influence on the filler's characteristics involved in performance and effectiveness (i.e., injectability, spreadability, lifting capacity, duration, etc.) [61]. The soluble fraction of the biopolymer may vary significantly among different fillers and the declared HA concentration in commercial fillers may not directly correlate to the final gel behavior [62]. Usually, physicians are not informed about how much soluble HA is included in the filler and, for this reason, the total concentration of commercially available HA fillers can only be a reference value rather than an absolute parameter for assessing filler performance [44]. ...
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Hyaluronic acid (HA) fillers have become the most popular material for facial volume augmentation and wrinkle correction. Several filler brands are currently on the market all around the world and their features are extremely variable; for this reason, most users are unaware of their differences. The study of filler rheology has become a wellspring of knowledge, differentiating HA fillers, although these properties are not described thoroughly by the manufacturers. The authors of this review describe the more useful rheological properties that can help clinicians understand filler characteristics and the likely correlation of these features with clinical outcomes.
... [22] The HA rheological properties should be considered when used in subcutaneous implantation, [23] because higher viscosity with a more expressive amount of crosslinking is needed to give effective volume to deep soft tissues, [24,25] mainly in the correction of Class II orthodontic patients. A larger amount of material is necessary for effective filling of the chin and mandible because HA deposits are made in the subperiosteal, subcutaneous and middle dermis regions of the chin and posterior jaw, [26] and some risk conditions may happen in these procedures. ...
Hyaluronic acid fillers can be used for the correction of facial soft tissue in orthodontics patients instead of orthognathic surgery. These clinical cases show the aesthetic results of Sattler MedBeauty Seven Protocol (SMSP) in five Class II female patients after having undergone orthodontic treatment. They had the lower third of the face filled with cross-linked hyaluronic acid (e.p.t.q. S500®), according to the SMSP. All patients were evaluated before and after treatments through an inquiry on adverse events, a Numerical Visual Scale (NVS), a self-assessment questionnaire (SQ) and the analysis of photographic records (PRs). The results showed oedema, pain and haematoma as the most cited adverse events, a score of 10 in the NVS for all patients, and a good aesthetic effect of chin and mandible in SQ and PR. The results suggest that SMSP is favourable in the aesthetic correction of chin and mandible in class II orthodontic patients using e.p.t.q. S500® for compensatory filling.
... O Ácido Hialurônico (AH), é um material bioidêntico (isto é, apresenta similaridade bioquímica ao naturalmente produzido pelo próprio organismo), diferentemente dos demais materiais preenchedores, como o ácido polilático e hidroxiapatita, e que podem causar reações imunológicas tardias (LEE; KIM, 2015). O AH é classificado como reabsorvível, e é uma molécula da família dos carboidratos que está presente nos tecidos conjuntivos, incluindo a matriz extracelular do tegumento (GUTOWSKI, 2016). ...
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Occlusion management in Implant Dentistry
... HA biomaterials have a long history of clinical use for ophthalmic and orthopedic applications. 26,27 While previous studies have demonstrated that HA biomaterials can reduce inflammation and scarring while promoting angiogenesis after SCI in rodents, these studies reported poor infiltration of cells and axons and integration with host tissue. 12,28 Here, we demonstrate that addition of a network of regularly structured, cell-scale macropores within HAbased scaffolds substantially increases infiltration of host cells and axons after SCI in a mouse model. ...
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Biomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is preferred to enable conformation to unique lesions and minimize tissue damage. While an interconnected network of cell-sized macropores is necessary for rapid host cell infiltration into—and thus integration of host tissue with—implanted scaffolds, injectable biomaterials have generally suffered from a lack of control over the macrostructure. As genetic vectors have short lifetimes in vivo, rapid host cell infiltration into scaffolds is a prerequisite for efficient biomaterial-mediated delivery of transgenes. We present scaffolds that can be injected and assembled in situ from hyaluronic acid (HA)-based, spherical microparticles to form scaffolds with a network of macropores (∼10 μm). The results demonstrate that addition of regularly sized macropores to traditional hydrogel scaffolds, which have nanopores (∼10 nm), significantly increases the expression of locally delivered transgene to the spinal cord after a thoracic injury. Maximal cell and axon infiltration into scaffolds was observed in scaffolds with more regularly sized macropores. The delivery of lentiviral vectors encoding the brain-derived neurotrophic factor (BDNF), but not neurotrophin-3, from these scaffolds further increased total numbers and myelination of infiltrating axons. Modest improvements to the hindlimb function were observed with BDNF delivery. The results demonstrate the utility of macroporous and injectable HA scaffolds as a platform for localized gene therapies after SCI.
Hyaluronic acid (HA) is a commonly used injectable material in temporary vocal fold injections (VFI) in patients with unilateral vocal fold paralysis (UVFP). Hyaluronic acid has generally been known for its three–six months of longevity following VFI. Owing to recent advances in cross-linking technologies, the longevity of HA-based materials, including deep-volumizing cross-linked HA used in VFI, has been improved. However, persisting injectable material in the subepithelial space poses undesirable complications following VFI. Herein, we report 2 cases of unexpected persistence of superficially injected cross-linked HA. In the first case, a 70-year-old man with iatrogenic UVFP received VFI with cross-linked HA three years ago and was referred for persistent dysphonia. Previously injected HA spilled out from the vocal fold (VF) when an epithelial incision was made in the subepithelial cystic lesion. In the second case, a 72-year-old woman with iatrogenic UVFP received VFI with cross-linked HA that migrated into the subepithelial space. Diffuse swelling of the injected VF caused dysphonia that lasted for a year. The previously injected HA spilled out when an epithelial incision was made in the swollen VF. Since superficially injected deep-volumizing cross-linked HA can persist for up to three years, laryngologists should be aware of possible sequelae upon suboptimal VFI with cross-linked HA.
The ideal material for a vocal fold injection augmentation for unilateral vocal fold immobility depends on the immobile vocal fold’s likelihood to recover function through natural nerve healing. In cases of permanent immobility from an issue related to arytenoid joint pathology or paralysis due to a neurologic injury or illness, durable or permanent materials are chosen. Shorter acting augmentation materials can be utilized in the setting of immobility when (1) the permanence of the condition is yet to be determined, or (2) due to coexisting other glottic pathology, the outcome of unilateral injection augmentation is unclear (Mallur and Rosen. Clin Exp Otorhinolaryngol. 3(4):177-82; 2010). This chapter will cover the materials available for vocal fold augmentation, focusing on non-autologous injectables that are available “off-the-shelf.”
Background: One of the earliest but often unaddressed signs of facial aging is volume loss in the temple. Treatment of the area can produce satisfying results for both patient and practitioner. Objective: Safe injection requires explicit knowledge of the anatomy to avoid complications related to the multitude of vessels that course throughout the region at various depths. The authors aim to detail the anatomy of the area and provide a safe and easy-to-follow method for injection. Materials and methods: The authors review the relevant anatomy of the temporal region and its application to cosmetic filler injections. Results: The authors describe an easy-to-follow approach for a safe and effective injection window based on numerous anatomical studies. Injection in this area is not without risk, including potential blindness. The authors review the potential complications and their treatments. Conclusion: Hollowing of the temple is an early sign of aging that, when corrected, can lead to significant patient and practitioner satisfaction. Proper anatomically knowledge is required to avoid potentially severe complications. In this study, the authors present a reliable technique to safely and effectively augment this often undertreated area of the aging face.
Objective: This trial compares the effectiveness and safety of HYC-24L (Juvéderm Ultra XC; Allergan plc, Dublin, Ireland) (24 mg/mL of hyaluronic acid, 0.3% lidocaine) and CPM-22.5 (Belotero Balance; Merz Aesthetics, Raleigh, NC) (22.5 mg/mL of hyaluronic acid) for the treatment of perioral lines. Materials and methods: Men and women aged 35 years or older with moderate-to-severe perioral lines were recruited for this randomized controlled, rater-blinded, 2-arm trial. The primary endpoint was a comparison of rater-assessed responder rates by the validated 4-point Perioral Lines Severity Scale at Month 6; responders were those who showed a ≥1 point improvement. A secondary endpoint was subject-assessed change in perioral lines measured by the Global Assessment of Change Scale. Results: A total of 136 subjects received treatment and 132 completed the trial (mean age: 58 ± 8 years). Total volume injected was 1.18 mL (HYC-24L) and 1.32 mL (CPM-22.5). At Month 6, a significantly greater proportion of HYC-24L subjects responded to treatment (87%) than CPM-22.5 subjects (72%) (p < .04). At all time points, HYC-24L subjects reported significantly greater improvement in their perioral lines than CPM-22.5 subjects, with the greatest difference at Month 6. No unexpected adverse events occurred. Conclusion: HYC-24L subjects showed a higher response rate and a greater improvement in their perioral lines than CPM-22.5 subjects for up to 6 months.
Background: Although the use of filling agents for soft-tissue augmentation has increased worldwide, most consensus statements do not distinguish between ethnic populations. There are, however, significant differences between Caucasian and Asian faces, reflecting not only cultural disparities, but also distinctive treatment goals. Unlike aesthetic patients in the West, who usually seek to improve the signs of aging, Asian patients are younger and request a broader range of indications. Methods: Members of the Asia-Pacific Consensus group-comprising specialists from the fields of dermatology, plastic surgery, anatomy, and clinical epidemiology-convened to develop consensus recommendations for Asians based on their own experience using cohesive polydensified matrix, hyaluronic acid, and calcium hydroxylapatite fillers. Results: The Asian face demonstrates differences in facial structure and cosmetic ideals. Improving the forward projection of the "T zone" (i.e., forehead, nose, cheeks, and chin) forms the basis of a safe and effective panfacial approach to the Asian face. Successful augmentation may be achieved with both (1) high- and low-viscosity cohesive polydensified matrix/hyaluronic acid and (2) calcium hydroxylapatite for most indications, although some constraints apply. Conclusion: The Asia-Pacific Consensus recommendations are the first developed specifically for the use of fillers in Asian populations. Clincial question/level of evidence: Therapeutic, V.
Background: Globalization marks an important change in the world's perception of elective procedures: patients are becoming consumers and cosmetic procedures are being viewed as commodities. The quest to achieve and preserve a youthful appearance has no geographic boundaries or ethnic limitations. Cosmetic injectables have become an increasingly popular treatment option designed to improve and preserve facial appearance. Hispanic (Latino) patients are one of the rapidly increasing ethnic groups worldwide, seeking injectable treatments. Methods: The author evaluated the trends in the use of injectables in his practice, mainly in Hispanic (Latino) patients, during one of the year's busiest seasons, specifically December 2014. Results: The results reflect Latino patients' behavior toward injectables and how a high-volume injector addresses the needs of patients, taking into consideration ethnic characteristics and socioeconomic factors in balance with the provider plan for cosmetic improvement or facial restoration. Conclusions: The author's Latino-Hispanic patients have embraced the concept of "less invasive" facial rejuvenation, and in his experience, he has found that their goal is to achieve precise results in a natural manner. Ethnicity does not play a role in patients' behavior toward cosmetic procedures. This "behavior" tends to be related more to the socioeconomic status and/or the level of education, rather than ethnicity, which move the patient toward specific procedures.
The contemporary male look includes sharp contours of the face with strong nose, significant malar-midface structure, and a powerful chin with well-defined jawline. Neurotoxins in the upper facial lines should preserve a lower position of the brows and flatter arch in men. Excessive lifting of the eyebrows and full correction of forehead and periorbital lines are not desirable. The use of dermal fillers is fully accepted into the nasolabial. Male patients with sagginess and hollowness related or not related to acquired lipodystrophies are candidates for cheek correction with volumizers. Female attractiveness lies in the cheekbones, and for men, it lies in the chin. The use of volumizers in the chin is very much appreciated by male patients, especially when it is recessed. A strong and masculine appearance is obtained by creating a square chin. Men present slight thinner lips, especially the upper one. Lip reshape in male patients is very much rejected. It requires expertise both in communication and in technical skills to convince male patients to undergo lip treatments with fillers. The use of injectables in male patients is growing. Neurotoxins in the upper facial lines and the use of dermal fillers in the nasolabial folds are widely accepted. The use of volumizers in the chin is highly appreciated. There is clear need of volumizers in the cheek to correct sagginess and hollowness in men. However, proper communication and technique are required. The same applies for the lips. Cheek and lip reshape is still considered a taboo for most patients and injectors.
Background: Fine lines and crepey skin are dermal manifestations of multilevel, age-related volume loss. It is, therefore, logical to combine intradermal volumetry for fine lines with subcutaneous volumetry for contours. This publication provides evidence- and experience-based rationales for application of cohesive polydensified matrix hyaluronic acid filler (Belotero Balance). Methods: Evidence level II data demonstrate efficacy of this product and longevity for up to a year or more with intradermal, superficial blanch injection. Its softness, flow tendencies, and homogeneous tissue integration are informed by low elasticity (G') and viscosity, high cohesivity, and high tan delta. Ultrastructural analysis confirms variable-density cross-linking, intended to confer resilience, and absence of detectable particles, minimizing Tyndall effect. Results: Scientific properties of Belotero Balance predict its 3-dimensional tissue expansion with prominent horizontal vectoring. We define this as superficial flow volumetry. High cohesivity and resilience can maintain structural integrity in typically mobile facial areas with strong muscular forces, uneven pressure, and significant hyaluronidase activity. This facilitates a natural appearance, both in repose and animation. Conclusions: Based on available evidence and experience, cohesive polydensified matrix hyaluronic acid is a notably efficacious fine line filler. The ideal fine line filler would restore dermis structurally and dynamicaly-moving as one with it, efficaciously expanding it, withstanding mechanical stress, swelling minimally, and potentially stimulating collagenesis. The relative contributions of space-filling, water binding, and collagenesis have implications for efficacy. A focus of current research is to determine the impact of filler cohesivity and tissue integration on these ideal qualities.
Background: Soft-tissue augmentation with hyaluronic acid (HA) fillers has become one of the most popular cosmetic procedures performed. HA fillers represent safe and commonly used fillers. Several different HA fillers are available. The differences lie in the manufacturing process, allowing for tailored uses. A small-particle HA with lidocaine (SP-HAL; Restylane Silk; Galderma, Uppsala, Sweden) was approved by the US Food and Drug Administration in June 2014 but has been available for many years in Canada as Restylane Fine Lines and in Europe as Restylane Vital. Methods: Relevant articles were reviewed relating to the composition, effectiveness, and safety of SP-HAL. We also discuss the author's extensive clinical experience in the use of this product in Canada. Results: SP-HAL has demonstrated proven benefits for lip fullness, augmentation, and treatment of perioral rhytides. Although off-label in the United States, SP-HAL is also well suited for the treatment of superficial fine lines, including periorbital, forehead, marionette, and smile lines. In addition, it has also been used in the tear trough region. A novel application for SP-HAL includes use as a skinbooster with intradermal micropuncture. In this technique, small aliquots of product are injected so as to gradually rejuvenate the skin in areas such as the face and hands. Side effects of SP-HAL were generally transient and mild. The most common side effects were swelling, tenderness, bruising, pain, and redness. Conclusion: SP-HAL is an effective and safe HA filler with varied clinical uses.
The United States is becoming increasingly more diverse as the nonwhite population continues to rise faster than ever. By 2044, the US Census Bureau projects that greater than 50% of the US population will be of nonwhite descent. Ethnic patients are the quickest growing portion of the cosmetic procedures market, with African-Americans comprising 7.1% of the 22% of ethnic minorities who received cosmetic procedures in the United States in 2014. The cosmetic concerns and natural features of this ethnic population are unique and guided by differing structural and aging processes than their white counterparts. As people of color increasingly seek nonsurgical cosmetic procedures, dermatologists and cosmetic surgeons must become aware that the Westernized look does not necessarily constitute beauty in these diverse people. The use of specialized aesthetic approaches and understanding of cultural and ethnic-specific features are warranted in the treatment of these patients. This article will review the key principles to consider when treating African-American patients, including the average facial structure of African-Americans, the impact of their ethnicity on aging and structure of face, and soft-tissue augmentation strategies specific to African-American skin.
Background: Hyaluronic acids (HAs) are very popular temporary fillers with a very good safety record. Improvements and adaptations in clinical use are continuing. Methods: We have assessed the available literature to investigate the relatively new Vycross technology that uses a mixture of high- and low-molecular-weight HAs with a relatively low but varying HA concentration with enhanced cross-linking to produce a number of products that have differing clinical indications. Results: Voluma has the highest HA concentration at 20 mg/mL, a high G prime translating into lift capacity and cohesivity keeping the product capable to lift vertically adding structure, form, and volume, whereas Volbella has much lower concentration at 15 mg/mL, a lower G prime and cohesivity allowing it to be used in more a horizontal spreading fashion enabling a superficial approach to lips, lines, and more subtle depressions. Volift at 17.5 mg/mL HA is half way between the 2 other products, allowing more subtle lift capacity but retaining an element of spread making it a useful agent for the perioral region in general and in the treatment of fine lines. Conclusion: A range of products has been released that allows different components of facial structure, volume, and lines to be adequately addressed.
Hyaluronic acid injectable fillers are the most widely used dermal fillers to treat facial volume deficits, providing long-term facial aesthetic enhancement outcomes for the signs of aging and/or facial contouring. The purpose of this article was to explain how rheology, the study of the flow of matter, can be used to help physicians differentiate between dermal fillers targeted to certain areas of the face. This article describes how rheological properties affect performance when filler is used in various parts of the face and exposed to mechanical stress (shear deformation and compression/stretching forces) associated with daily facial animation and other commonly occurring external forces. Improving facial volume deficits with filler is linked mainly to gel viscoelasticity and cohesivity. These 2 properties set the level of resistance to lateral and vertical deformations of the filler and influence filler tissue integration through control of gel spreading. Selection of dermal filler with the right rheological properties is a key factor in achieving a natural-looking long-lasting desired aesthetic outcome.