Basics of Dermal Filler Flashcards
(19 cards)
What are dermal fillers and what can they do?
Dermal fillers
-helps to restore the volume of the face (~fill) which we lose when we age due to loss of subcutaneous fat
-help to diminish the appearance of fine lines, wrinkles or hollowed areas
Fillers can be used for a variety of purposes:
-fine lines, wrinkles (crow’s feet, marionette lines, nasolabial folds, worry lines or laugh lines)
-hollowed areas (cheek or eye troughs)
-restore volume of lips
-skin dimpling from acne scarring
-scars from burns
How can you classify dermal fillers by:
-longevity
-biodegradability: biodegradable vs non-biodegradable fillers
-mode of action: passive tissue fillers vs stimulatory fillers
Types of dermal fillers
-longevity: some dermal fillers last longer than others
-biodegradable fillers like hyaluronic acid, calcium hydroxyapatitie (radiesse), collagen and poly-l-lactic acid (sculptra), last for a shorter period of time vs non-biodegradable fillers which are semipermanent like PMMA (bellafill) and silicone
-mode of action: passive tissue fillers like hyaluronic acid vs stimulatory fillers like caclcium hydroxyapatitie (radiesse) and poly-l-lactic acid (sculptra) which induce inflammation and endogenous neocollagenesis by fibroblasts
What are the different types of biodegradable fillers?
- Bovine collagen
-bovine collagen: first soft tissue filler approved by FDA:Duration of action 6 months. stopped using it due to rare side effects like foreign body granulomas and anaphylaxis - human collagen
-human collagen was used in place of bovine collagen due to side effects. Collagen was harvested from skin in the form of intact collagen fibrils-> made injectable autologous human tissue matrix. Collagen was also harvested from donors that went through extensive screening and irradiation. Duration of action 7 months. - hyaluronic acid
-glycosaminoglycans (GAG) made of long chain of disaccharide molecules (glucoronic acid) and D-acetylglucosamine. 50% of HA is found in the skin. It is produced by endothelial cells, synovial cells that line synovial membranes, dermal fibroblasts, oocytes. It has both a passive tissue filler and stimulatory effect. When water is attracted to HA (hydrophilic), it is thought to swell to reduce compressive forces. It is also thought to stimulate fibroblasts to cause neocollagenesis.
(to be continued)
What are the different types of biodegradable fillers?
-poly-l-lactic acid (sculptra); how does this work; when was it improved by the FDA; what are some of the side effects
-calcium hydroxapatite (radiesse); how does this work; for what use was it approved by the FDA for; how long does the scaffold take to be broken down; what are the pros and cons
-polycalprolactone (ellanse); how does this work; what is the structure of ellanse and what makes this more durable; what is it used for
-cross linked carboxymethylcellulose (CMC); what is this used for? what are the pros of CMC? (G’)
-autologous fat injection: what are the different types? what are the cons?
- poly-l-lactic acid (sculptra)
-biocompatible, biodegradable, biostimulatory filler. It stimulates dermal fibroblasts to cause neocollagenesis. It causes an increase in dermal thickness due to increase in type 1 collagen over 8-30 months once injected. It was approved for FDA use in July 2009.
-it is known to cause side effects like granulomas (44%) which need to be surgical excised and treated with intralesional corticosteroids (triamcinolone) - calcium hydroxapatite (radiesse)
-biocompatible, biodegradable, biostimulatory filler. It acts as a scaffold for collagen production. CaHA is carried in tiny microspheres suspended in gel carrier. Once injected, it causes an immediate increase in volume and stimulates fibroblasts to produce collagen. Gel is absorbed by the body and CaHA is left behind-> metabolised by the body.. leaving behind new collagen. (same pathway as bone debris metabolism). It is approved by the FDA for use of moderate to severe wrinkles and facial lipoatrophy in HIV patients.
Once injected, full appearance from the implant. But as the gel and CaHA is absorbed and broken down, this diminishes within 9-12 months.
It is not used in lips due to high incidence of nodules. It is not reversible like HA hence it tends to not be used.
It is not known to cause foreign body reactions like granulomas.
- polycalprolactone (ellanse)
-biodegradable, biostimulatory filler. PCL is suspended in 70% CMC gel. It has polymers of different chain lengths, making it more durable and stronger. It is a one-off treatment and has 4 types of formulations that have different durability. It is thought to stimulate collagenesis for up to 13 months once injected.
-it is used as a suture material; in orthopedic implants; by plastic surgeons to complement existing procedure and experienced aesthetic practioners
- cross linked carboxymethylcellulose (CMC) C for carrier
-used in the pharmaceutical industry as a carrier for antibiotics; oral NSAIDs like ibuprofen/ampicillin; injectable steroids like dexamethasone; drug delivery like nifedipine/ibuprofen; as well as soft tissue fillers like ellanse and radiesse
-pros of CMC is that it has low incidence of inflammatory reactions as CMC is derived from plant sources with no protein residues or bacterial endotoxins. It also has high G’-> lasting for a long period of time and able to withstand sheer forces like skin tension
- autologous fat injection
-PRP injections (platelet rich plasma) and cell-assisted transfer from adipose derived stem cells are revolutionizing techniques in the aesthetic surgical industry that are less invasive.
-however it has cons due to complications like vision loss/stroke after injecting glabella or nasolabial folds. It also has inconsistent resorption rate and longevity.
What are the different types of permanent soft tissue fillers?
What are some of the side effects of permanent soft tissue fillers?
Why is it not advisable to use biodegradable soft tissue fillers in patients with permanent filler?
-paraffin; why is this no longer used?
-polymethylmethacrylate (PMMA) what is this used for? describe the structure of PMMA. What are the side effects? What are the ocular side effects?
-aquamid (polyacrylamide hydrogel) what is this used for? What are some of the side effects?
-Silicone: what is this used for? why is it rarely used and only by experienced practioners? What are the side effects?
Permanent soft tissue fillers should only be used by experienced practitioners. They are not reversible and cause a range of side effects like granulomas, nodules, allergic reactions. It is not advisable biodegradable soft tissue fillers in patients with permanent filler due to the risk of introducing infection to the permanent filler.
types of permanent soft tissue fillers
-paraffin: no longer used due to risk of paraffinomas/granulomas
Polymethylmethacrylate (PMMA)
-polymethylmethacrylate (PMMA) a.k.a primefill is a rigid, clear, thermoplastic skin filler. It is known to be low cost and durable and can be used for treatment of moderate to deep wrinkles/folds. It is also used in permanent surgical implants.
-cons: it causes side effects especially in nasolabial folds, lips, periocular regions. It can cause nodules, inflammation, allergies and skin hypopigmentation. In the periocular region, it can cause fibrotic nodules, erythema and oedema and eyelid malposition. This may require surgery to correct.
Aquamid
-aquamid (polyacrylamide hydrogel). Once injected, it is surrounded by macrophages and fibroblasts-> preventing migration.
-aquamid is not approved by FDA and only some european countries for facial and body augmentation; and correct HIV lipodystrophy
-cons: some reports of granulomas, inflammation and allergic reaction for aquamid
Silicone
-injectable silicone should only be used by experienced practioners due to side effects and non-reversability. It is highly technique sensitive.
-uses: it is used in permanent surgical implants. injectable silicone oil is used in opthalmic surgery like retinal tears etc.
-silicone is known to cause adverse effects that that can last for many years like permanent scarring, fibrotic nodules. It can also embolize and migrate in the body-> making it difficult to be removed
To be continued->
Describe these permanent dermal fillers
-polyvinylpyrrolidone-silicone (PVP); describe the structure of this; what is this used for; what are the side effects
-polyalkylimide gel
-polyvinylhydroxide in polyacrylamide gel
-polyvinylpyrrolidone-silicone (PVP) is made of silicone polymer surrounded by PVP carrier. Once injected, collagen encapsulates it in a ratio higher than 1:1. Implant stays in site injected and avoids being phagocytosed by macrophages due to large silicone particles.
-PVP-silicone is used in lip augmentation and correction of facial rhytids. It causes side effects like granulomas, swelling.
-polyalkylimide gel is a translucent, hydrophilic, permanent filler that is similar to aquamid but more durable. It is used by plastic surgeons for the correction of facial lipodystrophy in HIV, gluteal atrophy, skin scarring, filling of pectus excavatum
polyvinylhydroxide in polyacrylamide gel is rarely used in lip augmentation. Not well researched.
What are the contraindications of dermal filler?
Contraindications of dermal filler:
-allergies to local anaesthetic agents like lidocaine; to hyaluronic acid; severe allergies/anaphylactic reaction
-skin cutaneous disorder or local infection/inflammation at site
-pregnant/breastfeeding/undergoing IVF treatment
-mental health problems like body dysmorphic disorder
What are some of the common side effects of filler?
What are the adverse effects to warn them about?
What aftercare advice would you give regarding filler?
-things to avoid
Common side effects of filler include:
-redness, swelling at the injection site (subside within a few days)
-temporary lumps/nodules
-assymetry
-overtreatment or undertreatment of area
Adverse reactions to filler:
“If you notice any changes in the colour of skin or pain around the area, it’s important to notify us as soon as possible as this could mean blood supply to the area has been affected.”
-infection (e.g abscess in injection site, aseptic technique v important)
-vascular occlusion causing:
a. skin necrosis-mottling of skin/skin discolouration like pale or greyish/pins and needles/pain
b. blindness
c. allergic reactions, anaphylaxis
Aftercare advice:
-avoid touching the face including massages or applying makeup to the area for at least 12 hours
-avoid strenuous exercise for 48 hours
-avoid alcohol, aspirin and ibuprofen for 48 hours
-avoid areas of extreme temperatures like saunas and minimise sun exposure for 1 week. It is important to protect skin with SPF
-avoid treatments like chemical peels, microdermabrasion, sun beds for 14 days
-you may drive after treatment but avoid flying as cabin pressure changes may cause swelling in face
-if there is bruising, you can apply topical arnica cream
What is the history of soft tissue fillers?
-1893
-1937
-1950s
-1970-1980s
-2003
-2007
What is the history of soft tissue fillers?
-1893: first fat transplant by Neuber, a german surgeon. Was used for soft tissue augmentation from arms to face
-1937: hyaluronic acid was extracted from bovine vitreous fluid. This was used in medical and cosmetic field for eye surgery, joint surgery for arthritic joints, volume restoration.
-1950s: liquid silicone injections
-1970-1980s: animal-based collagen implants
-2003: FDA approved restylane (HA from bacterial fermentation). Public demand for high quality aesthetic treatments and minimal downtime. Research into dermal fibroblast cultures and collagen to make stimulatory fillers
-2007: american academy of aesthetic plastic surgeons reported that they’ve treated 1.75 million patients with fillers
Hyaluronic acid:
What is the structure of HA?
How long does it take for endogenous HA ito be metabolised?
What are the functions of HA?
Hyaluronic acid is a glycosaminoglycans made of disaccharide molecules (glucoronic acid and D-acetylglucosamine). Held by 1,4-BDDE bonds
Endogenous HA is metabolised within 24-48h.
Functions of HA:
1. hydration of tissue
-hydrophilic and absorbs/retains water to create a water-rich extracellular matrix to support cell activities
2. cell to cell signaling and cellular movement
3. wound repair
-signals to immune cells to migrate to damaged wound; causes immune cell proliferation
3. ECM supports collagen and elastin
4. stimulates fibroblasts for neocollagenesis
Hyaluronic acid:
What are the 3 stages in the lifecycle of HA?
What are the factors that affect degradation of HA?
Hyaluronic acid:
What kind of HA would you inject in a deeper placement? (in terms of G prime, cross links, HA concentration)
What kind of HA would you inject in a superficial placement?
(in terms of G prime, cross links, HA concentration)
What is your reasoning behind this?
Manufacture of exogenous hyaluronic acid:
What are the 4 stages in the manufacture of exogenous HA? ( think about steps in process)
What is the difference between biphasic and monophasic filler?
What is a polydensified monophasic gel?
Manufacture of exogenous hyaluronic acid:
1. HA fillers are made via a microbial fermentation (bacteria and yeast) with HA substrates.
- HA concentration is determined. Higher HA concentration will have greater longevity and are more suitable for filler products in deeper placement
- cross linkages, (1,4 BDDE), between chains are made. More cross linkages-> more resistant to enzymatic degradation and free radicals
- particulate size of the filler product-> needs to be small enough for fine bore needle to withstand extrusion forces
Particle size is specific to filler use. May be made into either a) monophasic gel with one type of size-> suitable for natural, delicate areas b) biphasic with 2 different types of sizes for deeper areas
Polydensified monophasic gel:
-e.g Belotero filler; after particulate sizing, 2nd stage of cross-linking
Hyaluronic acid:
What is immunogenicity?
What contributes to immunogenicity of HA?
Immunogenicity- ability of HA to cause an immune response
This depends on a few factors:
1. cross-linking agents used and bacterial endotoxins in microbial fermentation
2. shape of the product (depending on the cross-links)-> contribute to immunogenicity
Manufacture of hyaluronic acid:
Rheological definitions:
What is G’?
What is cohesivity?
In terms of G’ and cohesivity,
what kind of fillers would you use in the:
-periocular area
-cheek area where you need volume and lift and there are high extrusion forces
-periorbital area
Rheological definitions:
G’
-also known as elasticity module, refers to the firmness of the filler gel and ability to withstand mechanical forces. Mechanical forces include:
-extrusion force during injecting
-compressive forces during facial muscle movement
High G’ products are more firm and able to withstand mechanical forces. They are better in deeper placements like lateral zygoma and cheekbone
Cohesivity
-ability of product to stay together despite mechanical stress
-cohesivity of HA product depends on no. of cross links and HA concentration. The greater the no. of cross links and ther higher the conc-> more cohesive
More cohesive HA-> better for deeper placements as they are able to withstand compression during facial muscle expression and retain shape-> e.g lateral zygoma
Manufacture of hyaluronic acid:
What is viscoelasticity?
How do you measure viscoelasticity of a HA product?
Rheometer measurements of viscoelasticity:
Elasticity modulus: What is a normal G’ measurement of HA? (in Pascals)
Viscosity: What is yield stress? What is viscosity? What is yield stress of HA (in pascals or N*)
Explain this in simple terms
Viscoelasticity
-viscosity refers to the state of produce being a thick fluid; resistance of products ability to flow once its moving
-yield stress refers to minimum stress needed to cause product to become liquid enough to start moving
-elasticity refers to the ability of the product to return back to its original shape after compressive forces/stress
Viscoelasticity is measured via a rheometer
-equipment consisting of 2 plates that can oscillate at different frequents and apply different mechanical forces
Rheometer measurements of viscoelasticity:
Elasticity modulus: What is a normal G’ measurement of HA? (in Pascals)= 150-320 Pa. Ability of the product to withstand compressive forces. This numerical measurement in Pa is the pressure needed to compress and deform HA
Viscocity: What is yield stress of HA (in pascals or N)=42-55 Pa or 0.35-0.54 N. Yield stress refers to the stress needed to cause product to thiner and more liquidy so it starts to flow. Measure this w the frequency of oscillations of the rheomater
Manufacture of hyaluronic acid:
Rheological terms
What does it mean by particle size? What is the normal particle size of HA? What does monophasic vs biphasic mean?
What does it mean by molecular weight?
What does it mean by structural strength/G’? What is the range in pascals?
What determines mechanical stability of a gel? What is the normal mechanical stability of HA? (%) What does it mean by monophasic monodensified gels? (give example)? What does it mean by biphasic polydensified gels?
What is cohesivity? How do you calculate this using G’? How do you determine cohesivity of a product? What is yield stress? What is C’ min?
Manufacture of hyaluronic acid:
Rheological terms
particle size-size of product in um (micrometer). normal particle size of HA- 203-480 um. monophasic (one size) vs biphasic (2 sizes)
molecular weight-sum of all the atomic masses
structural strength/G’-firmness of the gel and its ability to withstand compressive forces? measured by oscillations in rheometer. G’ of HA-105-700Pa
mechanical stability of a gel-determined by no. of cross links normal mechanical stability of HA? (1-10%) monophasic monodensified gels like juvederm (monophasic meaning one size and monodensity meaning single uniform density) biphasic polydensified gels like belotero (biphasic meaning 2 sizes and polydensity meaning different density) different particulate sizes of different densities due to addition of extra HA and second cross-linking stages
cohesivity- ability of a product to return back to its solid state after its viscous state; measured by 100X G’‘/G’? (%) yield stress-minimum stress needed to turn produce into viscous liquid state from solid state
C’ min-ability of fully hydrated HA to withstand breakage of cross-links when dissolved in solvent
Hyaluronidase:
What is the diff between large vs small volume protocol?
What is the indication to use large vs small volume
Large volume (dilute in 10ml) but low concentration. 1500U in 10ml of saline
Small volume (dilute in 1/2ml) but high concentration. 1500U in 1 or 2 ml of saline
Indication for large or small volume protocol:
Small volume but high conc protocol
-for emergency scenarios like vascular occlusion or retinal occlusion
Large volume but low conc protocol
- for non-emergency scenarios like correction due to product misplacement (tyndall’s effect)
-filler migration
-haematoma
- hypersensitivity or allergic reaction to filler, overcorrection/assymetry
Hyaluronidase
MOA-how does hyaluronidase work
What is the half life and duration of action of drug? How is it inactivated?
What are the absolute contraindications to hyaluronidase?
What are the possible drug reactions?
What is the brand name of drug in UK?
Storage of drug:
What temp do you need to store hyaluronidase at
Pharmacology of drug-
Hyaluronidase is enzyme that breaks BDDE linkages
Half life of drug: 2-10 min; duration of action 24-48h
Absolute contraindications:
-pregnancy/breastfeeding
-allergic reaction to hyaluronidase or allergy to insect bites/stings (saliva of biting or stinging insects have hyaluronidase)
-malignancy/infection at potential injection site
Drug reactions:
-antihistamines or ibuprofen can cause resistance to hyaluronidase
Brand name of drug in UK: Hyalase (wockhardt)
Storage of drug
Drug needs to be stored at cold temps 2-8 degrees. If stored at 25 degrees or more, it wont last for a long period of time (stability only for 12 months)
What is an intradermal patch test and what is this used for?
How do you perform intradermal patch testing?
What is a positive test?
Intradermal patch testing to check for allergies to hyalase before using a large volume protocol for filler dissolution-tyndall effect, non-inflammatory nodules, product migration etc.
Intradermal match testing:
Control-0.2ml of normal saline
Hyalase-0.2ml (30U) of hyalase (large volume protocol). Dilute 1500 U of hyalase in 10ml of bacteriostatic saline saline.
Positive test
>8mm
-wheal
->50% increase in size
