Dr.
Neelam Ayub
FCPS Dermatology
Hyaluronic Acid Fillers
In USA over 3.5 million procedures
More than 95% HA based procedures
Types of Fillers
➢ There are 160 Dermal Fillers
➢ 50 companies are making these products worldwide
➢ More are jumping into this billion dollar industry
BASICS OF DERMAL FILLERS
Dermal fillers can be
a. Autologous Implants
b. Collagens
c. Hyaluronic Acid(HA)
d. Biosynthetic materials
Types of commonly used fillers
Temporary fillers
Cross linked Hyaluronic acid fillers
Longer lasting fillers
Calcium hydroxilapatite filler
Biostimulators
Polycaprolactone
Permanent fillers
Polymethylmethaacrylate
HA FILLERS
Monophasic
Biphasic
Monophasic fillers
Homogeneous mixture of high and low molecular weight
HA
Monodensified
Polydensified
Biphasic fillers
Heterogenous , cross-linked HA of specific size suspended in a
mixture of non cross-linked HA vehicle
More rheological stability
Hyaluronic Acid
Naturally Occur in Connective Tissue, human dermis
and synovium.
More than 50 percent of body HA is in skin
Half life 1-2 days (degraded by enzymes and
Radicals)
Conti..
Modification of Hyaluronic Acid
Cross Linking
a. Butanediol Diglycidyl Ether(BDDE)
b. Divinyl Sulfone (DVS)
Concentration of non extractable and extractable HA
HA molecule size
Effects of Modificatications
a. Cohesiveness
b. Gel Hardness
c. Swelling Ratio
d. Resistance to degradation
e. Usage and site specification
What is rheology of dermal fillers
➢ Studyof how a material deforms and reacts under
mechanical stress.
Clinical implications of Rheology
Biocompatibility
Longevity
Ease of injection
Appropriateness for site
Complications
RHEOLOGY
Rheology..
RHEOLOGY
MAIN RHEOLOGICAL PROPERTIES
a. Viscoelasticity and Shear Deformation
b. Cohesivity
c. Viscosity and Extrusion Force
Viscoelasticity and Shear Deformation
➢Property of an HA filler, exhibiting both viscous
and elastic behavior when undergoing shear
deformation.
RHEOLOGY
Different Manufacturing technologies
➢ G* measures overall viscoelastic properties or “hardness”
➢ G’ measures elastic properties
➢ G” measures viscous properties
➢ and tan delta measures the ratio between viscous and elastic properties
G’ MODULUS
G Prime or Elastic Modulus
Measure of a gel’s resistance to deformation
Measures the Ability to rebound to its original
shape. High elasticity rubber band & low elasticity
syrup..
Cont…
HigherG’ fillers are used in deeper planes like
nasolabial and marrionette lines
Lower G’ fillers are used in superficial planes like
wrinkles around mouth and eyes.
Cont..
Gelswith higher G prime better resists dynamic
forces during muscle movements providing better
potential lift and longevity.
Gels with lower G are less cross-linked therefore
facilitate ease of injection and lower risks of lumps
and bumps
Viscosity and Extrusion Force
Viscosity is a measure of a filler’s resistance to flow
when shear stress is applied such as may be exerted
upon a filler both during and after injection.
Viscosity is not relevant to performance after the filler
has been implanted.
An Ideal HA filler is one with low extrusion force
allowing for ease and précised dosing during injection.
In a Rheology Paper for HA filler a peanut butter is cited as
high viscosity gel while butter is cited as low viscosity gel.
Cohesivity
Cohesivity characterizes how the filler behaves as a gel
deposit once it is implanted in the face.
Cohesivity is strength of cross-linking adhesion forces
that hold the individual HA units together.
Factors Determinig Cohesivity
a. Concentration Of HA filler
b. Degree of Cross-linking
Clinical Significances Of Cohesivity
Maintains vertical projection
Cohesivity
Filler G’ (Pa) G” (Pa) Tan d Compression (gmf)
Juve´ derm Ultra XC 207 80 0.39 96
Juve´ derm Ultra Plus 263 79 0.30 112
XC
Juve´ derm Voluma 398 41 0.10 40
XC
Juve´ derm Volift with 340 46 0.14 30
lidocaine†
Juve´ derm Volbella 271 39 0.14 19
with lidocaine†
Restylane-L 864 185 0.21 29
Perlane-L 977 198 0.20 32
Belotero Balance 128 82 0.64 69
Swelling ratio
Close to saturation
Unsaturated filler
How much water a filler will absorb after
It is implanted
Limitations of Rheology
Donot permitthe analysis of Poly-L-Lactic Acid Filler
(PLLA) and Polymethylmethacrylate (PMMA)Fillers.
Clinical effects of
these products are dependent on
neocollagenesis and not there physiochemical properties.
Mid Face
AIM DESIRABLE PROPERTIES
MID FACE
DEEPDERMAL OR SUB WITHSTAND SHEAR
DERMAL INJECTION DEFORMATION
RESTORING VOLUME WITHSTAND COMPRESSION
ACHIEVING PROJECTION MINIMAL DISPLACEMENT
MAINTAIN SHAPE
Mid Face
RHEOLOGICAL PROPERTIES
LOW VISCOSITY ( FOR EASE
OF INJECTION)
HIGH ELASTICITY
MEDIUM-HIGH COHESIVITY
Eg JUVEDEM VOLUME,
RETYLANE LYFT
Fine Lines and Lips
AIM
FINE LINES AND DESIRABLE
LIPS PROPERTIES
RESTORING VOLUME IN NON BULKING
ITRADERMAL AND SUB-
DERMAL PLANES
EASY MOULDING AND
SPREAD OF PRODUCT
Find Lines and Lips
RHEOLOGICAL PROPERTIES
FINE LINES
AND LIPS
LOW VISCOSITY
LOW-MEDIUM ELASTICITY
LOW COHESIVITY
Eg JUVEDERM VOLBELL,
RESTYLANE REFYNE
Lower Face
AIM DESIRABLE PROPERTIES
LOWER FACE
RESTORING VOLUME IN EASILY MOULDABLE
DEEP DERMAL AND SUB-
DERMAL PLANES MINIMAL PROJECTION
NON PALPABLE
Lower Face
RHEOLOGICAL PROPERTIES
LOW VISCOSITY
MODERATE ELASTICITY
LOW COHESIVITY
Eg JUVEDERM VOLIFT
Nose and Chin
AIM
NOSE AND CHIN DESIRABLE PROPERTIES
NASAL AND CHIN MINIMAL LATERAL SPREAD
PROJECTION
MAXIMAL VERTICAL
PROJECTION
Nose and Chin
RHEOLOGICAL PROPERTIES
NOSE AND
CHIN
LOW VISCOSITY
HIGH ELASTICITY
HIGH COHESIVITY
Eg JUVEDERM VOLUMA,
RESTYLANE LYFT
Significance of Rheological Tailoring
Rheological tailoring of dermal fillers allows the
pallete to be refined and individualized for each
patient and for each facial area thus optimizing
aesthetic outcomes, safety and patient satisfaction.
Complication of Fillers
➢ My aim of this small presentation is not to scare
you but to make you more smart in skills.
➢ Because the smarter you are, more things can
scare you and you become more careful.
CLASSIFICATION OF HA FILLERS
COMPLICATIONS
Injection site adverse effects
Mild usually last less than one week:
Pain
Erythema
Itching
Edema &Ecchymosis
○ Minimized by stopping the intake of aspirin, NSAID, supplements
containing ginkgo biloba, vitamin E, omeg-3, fish oil, ginseng
○ Before and after procedure use of arnica, topical vitamin K or
bromelin may decrease the post-injection ecchymosi
Injection site adverse effects
The Tyndall effect
placing the HA fillers too superficially and it manifests as
bluish discoloration
Which can be treated by injecting 15–50 IU of hyaluronidase
followed by massage
Hypersensitivity reactions
Acute or delayed localized hypersensitivity, which was
defined as ‘‘swelling, erythema, edema or angioedema
May be due to
NASHA gel
Protein contaminants
Abscess/cellulitis
Mycobacterial infection
Post filler bacterial infection with Mycobacterium abscessus
was reported in New York City in 2002 after a non-FDA
approved HA filler
Infections
Herpes simplex virus infection
History of recurrent herpes simplex outbreaks
prophylactic antiviral therapy in the form of valacyclovir 500
mg bid 2 days before the procedure and 3 days after.
Abscess/cellulitis
Mycobacterial infection
Post filler bacterial infection with Mycobacterium abscessus
was reported in New York City in 2002 after a non-FDA
approved HA filler
Vascular occlusion
Vascular occlusion is the most concerning complication
It can be a localized occlusion resulting in:
skin necrosis:
○ Results from either direct intravascular injection or the
compression of the vessels by the injected filler material
○ high risk facial zones for skin necrosis and embolization are the
glabella, nasal ala and dorsum of the nose
Vascular occlusion
Arterial occlusion due to intra-arterial injection
an immediate or early skin blanching and varying degrees of
pain;
if not treated swiftly, the affected skin will develop reticulated
erythema, purpura and ulceration and consequently, scarring
Delayed onset arterial occlusion secondary to external
compression by the injected filler
Glabellar necrosis
Blindness
Most feared complication of fillers injection.
Accidental high injection pressure of the supratrochlear,
supraorbital, and dorsal nasal arteries branches of
ophthalmic artery angular artery terminal branch of
facial artery (external carotid system)
Blindness
Result in a retrograde flow of the filler emboli into the
ophthalmic artery
Once the physician stops the pressure on the plunger,
the arterial pressure will push the filler emboli into the
retinal circulation resulting in the loss of vision
Minimize the risk of vascular complications
Several measures can be taken including:
Understanding of the facial anatomy
Aspiration before each injection
Low pressure injections of minimal volumes (<0.1
ml/injection)
Dilution of the filler with lidocaine and/or epinephrine,
Minimize the risk of vascular complications
keeping the needle moving (bolus injections should be given
only in the periosteum plane)
Avoid injections in areas of previous scarring
use of blunt cannulas, which may reduce the risk of
intravascular placement of the filler material
Mangment
If features of tissue necrosis appear.
The injection should be stopped.
An immediate injection of hyaluronidase enzyme is crucial
in order to minimize the amount of tissue necrosis (Beer et
al., 2012 ).
This enzyme acts by hydrolyzing HA by splitting the
glucosaminidic bond between C1 of the glucosamine
moiety and C4 of the glucuronic acid
Biofilms
A biofilm is a collection of bacteria surrounded by a
protective and adhesive matrix, which was first
discovered on dental plaques.
Biofilms use filler as a surface to attach and excrete
their own matrix and develop and resist antibiotic
treatment up to a thousand times more effectively.
Biofilms
Diagnosis can be confirmed using PCR of bacterial
protein
Macrolide and quinolone,with clarithromycin 500 mg
bid and ciprofloxacin 500 mg bid for 4–6 weeks
Hyaluronidase can help cleave and fragment the
enclosing matrix, helping the antibiotics work
Foreign body granuloma
Chronic inflammatory reaction that entraps a foreign
body, preventing its migration.
Cause:
Inability of the immune system to enzymatically degrade or
phagocytose the foreign body
The pathogenesis remains unknown
Foreign body granulom
Delayed onset after filler injections, appearing as red
papules, plaques or nodules with a firm consistency &
fibrosis in late stages.
Confirmed histologically
Intralesional hyaluronidase is an effective therapy for
granulomatous lesions secondary to HA filler
Product visibility and angioedema
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