Injectable Fillers Treatment & Management

Updated: Oct 26, 2017
  • Author: Deborah Yu, MD; Chief Editor: Deepak Narayan, MD, FRCS  more...
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Treatment

Medical Therapy

Medical therapy for the specific types of injectable fillers is discussed in the sections below.

Numerous fillers are available. Each of these preparations has special properties, indications, and contraindications.

Biodegradable fillers include bovine collagen, autologous fibroblasts (LAVIV, AlloDerm), hyaluronic acid (Juvadérm, Restylane), calcium hydroxylapatite (Radiesse), and poly-L-lactic acid (Sculptra). [2, 3]

Nonbiodegradable fillers include silicone (off-label) and polymethylmethacrylate beads (Bellafill). [4]

Fillers are used to fill defects within the skin and subcutaneous tissue. The depth of the defect should determine the filler chosen for the appropriate procedure. For example, collagen and hyaluronic acid are used to fill relatively superficial defects, while deeper defects may require fat or synthetic products, including implants or permanent fillers. Multiple fillers or implants may be layered to achieve maximal correction.

Commonly-used fillers

Hyaluronic acid-based fillers are the most commonly used (Belotero, Hydrelle, Juvadérm, PREVELLE Silk, Restylane). [5]  Other noncollagen fillers include polyacrylamide, fat, autologous fibroblasts, calcium hydroxylapatite, poly-L-lactic acid, and silicone.

A study by Jeong et al reported that injectable dermal fillers made of hyaluronic acid/hydroxylapatite composite hydrogel demonstrated better volumetric maintenance than did pure hyaluronic acid filler. According to the study, this was due to the composites’ lower water content and greater degree of biointegration with surrounding tissues. The composite fillers were also associated with improved dermal recovery, having encouraged the development of collagen and elastic fiber. [6]

Belotero Balance  [7]

Belotero Balance is approved by the FDA and is manufactured by Merz Aesthetics, Raleigh, NC. [8]

Belotero Balance is a hyaluronic-based dermal filler that is derived from streptococcal cultures and cross-linked with the binding agent 1,4-butanediol diglycidyl ether. It is indicated for correction of moderate-to-severe facial wrinkles and folds via injection into the mid-to-deep dermis. Belotero Balance is obtained in a sterile 1-mL prefilled glass syringe. Clinical trials showed that 1.5 mL per nasolabial fold was the average volume needed to obtain optimal correction. Belotoro Balance can be injected using a 30-gauge needle, which is attached to the syringe. Needles are provided to assure proper needle attachment. Adverse reactions include injection site symptoms, such as swelling, induration, erythema, pain, discoloration, and rash. Nonlocal adverse events, reported in 2.5% of study subjects, include mild herpes simplex, mild headache, and moderate urticaria.

Fat

Fat injections have been available and performed for more than 100 years as live, free fat grafts. Liposuction has made the harvesting of fat a simpler procedure. For grafting, this is performed with a syringe in an atraumatic manner. The best donor sites include the thighs, buttocks, knees, and abdomen. The resultant fat is then centrifuged gently to separate the intact fat cells from supernatant serum-free lipid. Fat cells are then injected into a subcutaneous plane under larger scars with a 16- to 18-gauge needle or special cannula. Fat is used as a subcutaneous filling substance and is not indicated in dermal augmentation. Thus, it is reserved for large, atrophic defects that include skin and fat.

Juvadérm XC, Ultra XC, Voluma XC, Volbella XC

The Juvadérm family of products is approved by the FDA and are manufactured by Allergan (Dublin, Ireland). [9, 10, 11]  

Some formulations of Juvaderm contain lidocaine. Juvadérm is a gel containing cross-linked hyaluronic acid produced from Streptococcus equi bacteria. Juvadérm Voluma XC is indicated for malar augmentation to improve age-related, midface volume loss. [12]  Juvadérm XC fillers (Ultra XC and Ultra Plus XC) are indicated for correction of moderate to severe facial rhytids and depressions (nasolabial folds). [12]   Juvadérm Ultra XC is indicated for use in lip augmentation and for injection directly into the lips and perioral area. [12]   Juvadérm Volbella XC is indicated for correction of fine perioral rhytids. [9]

A multicenter, randomized, controlled study with 87 subjects demonstrated that at 24 weeks post injection with Juvéderm Ultra Plus, correction was  maintained in 96% of nasolabial folds injected and in 81% for one year or more. [13]  Subsequent treatment required a decrease in volume of Juvéderm.

The most common adverse events were swelling, redness, discoloration, and bruising as reported by postmarket safety surveillance of Juvéderm injectable gel in countries outside the United States. [14]

PREVELLE Silk  [15]

PREVELLE Silk is approved by the FDA and is manufactured by Genzyme Biosurgery in Ridgefield, NJ.

PREVELLE Silk is a hyaluronic acid dermal filler derived from bacteria that contains 0.3% lidocaine designed to decrease pain at the time of injection.

A prospective, randomized controlled trial comparing PREVELLE Silk with the same filler without lidocaine showed greater than 50% pain relief at every postinjection time point compared with the same filler without lidocaine. The largest difference in pain between the groups was seen at the time of injection.

Radiesse and Radiesse (+)

Radiesse (formerly known as Radiance) is approved by the FDA and is manufactured by Merz Aesthetics, Raleigh, NC.

Radiesse is an aqueous gel that contains microspheres of calcium hydroxylapatite. Hydroxylapatite has a much slower rate of resorption by the body and, so, has the potential to give a semipermanent result when used as a filler. Calcium hydroxylapatite does not elicit an inflammatory reaction, so no allergy testing is necessary. Only the (+) formulation of Radiesse contains lidocaine. Radiesse and Radiesse (+) are injected at the subdermal level to improve the appearance of severe facial rhytids and folds, such as the nasolabial folds. [16]  Radiesse is also used to correct lipodystrophy in patients with human immunodeficiency virus (HIV), as well as to correct volume loss in the dorsum of the hand. [17, 18, 19]

Restylane, Restylane-L, Restylane Lyft with Lidocaine (formerly known as Perlane-L), Restylane Silk 

These agents are approved by the FDA and are manufactured by Galderma, Lausanne, Switzerland. [20]

They are composed of hyaluronic acid derived from a bacterial rather than animal source. These products do not pose an allergy risk and are thought to be broken down at a slower rate than the collagen products. Results can last as long as 1 year. In 2012, the FDA approved a form of Restylane, called Restylane-L, that contains 0.3% lidocaine. Restylane and Restylane-L are used for lip augmentation and correction of volume deficits at the mid- to deep dermis. [21]  Restylane Lyft with Lidocaine is used for malar augmentation and correction of age-related, midface volume deficits. [21]  Restylane Silk is used for injection at the submucosal level for lip augmentation and at the dermal level for perioral rhytids. [21]

Sculptra

Sculptra is approved by the FDA and is manufactured by Dermik Aesthetics, a division of Sanofi-Aventis, Bridgewater, NJ.

Sculptra is a novel injectable filler that is composed of poly-L-lactic acid. [22]  This material has been used for years to make suture materials and is known to be highly biocompatible. It has been approved for treatment of HIV facial lipoatrophy. [23]  It is supplied as a freeze-dried material that can be reconstituted in sterile water at room temperature. Multiple treatments over several weeks are required for the best results; however, results can last up to 2 years.

Other, less commonly–used fillers (collagen)

Collagen fillers can be divided into those of bovine and human origin. Since the autologous forms are prepared from the patient's own tissues, they are not allergenic and do not run the risk of viral transmission.

  • Human collagen - Allogeneic (AlloDerm, Cymetra [micronized AlloDerm])

  • Bovine collagen – Bellafill

  • Porcine collagen - Permacol

Use of collagen fillers has declined with the increased use of products such as hyaluronic acids and poly-L-lactic acid. [24]

AlloDerm and Cymetra (human collagen)

AlloDerm and Cymetra are approved by the FDA and manufactured by LifeCell Corporation, Branchburg, NJ.

AlloDerm is an acellular human dermal graft processed from tissue bank–derived skin. It has been used since 1992 on more than several thousand patients; initially, it was used for burn victims and, later, in oral surgery and soft tissue augmentation. Because AlloDerm is available in sheets 1-2 mm thick, it is not injected but implanted surgically. Scar correction is theoretically the result of the ingrowth of tissue during the remodeling phase of wound healing.

Insertion requires the use of local anesthesia by nerve block, local infiltration, or both. After rehydrating the graft in normal saline, the dermal sheet is rolled and trimmed to the appropriate length of the defect. A tunnel is then created under the scar or contour deformity and an instrument is used to pass the tissue to the opposite side, where it may be sutured into place.

A clinical trial of 12 lip augmentation procedures showed no rejection or displacement at 12 months postoperatively. Suture site infection and reactivation of herpes labialis was reported. Results from AlloDerm last for approximately 6-12 months, but persistence of grafts can reach several years. AlloDerm appears to have greater longevity than collagen fillers, though no controlled studies have been performed.

Cymetra is a micronized form of AlloDerm that is injectable. This material is rehydrated with lidocaine in the physician’s office before injection. Because it is human-derived, no skin test is required by the manufacturer. Clinical trials of 200 patients to date show no evidence of allergic reactions; however, transient bruising, redness, and swelling occurred at a rate of 2.1%. Results last in the range of 3-6 months.

Bellafill (formerly, ArteFill) (bovine collagen)

Bellafill, under its former name, ArteFill, received FDA approval in 2006. The product's name was changed to Bellafill in 2014; in 2015, the FDA approved it for use in the treatment of acne scars. [25]

Bellafill is composed of polymethylmethacrylate beads suspended in bovine collagen. The beads remain intact as the collagen degrades. Polymethylmethacrylate acts as a foreign body, causing a local inflammatory response, and becomes trapped in the resultant fibrous connective tissue. [26]

Prior to injection of Bellafill, a special skin must be given. [27] Patients should not undergo injection with Bellafill if they have a positive skin test or 2 equivocal skin tests. [27] Patients with a higher-than-normal antibovine collagen serum immunoglobulin G level at baseline are advised not to undergo treatment with Bellafill. [27]

Permacol (porcine collagen)

Permacol (Medtronic, Minneapolis, MN), a porcine-derived product, is manufactured in either an injectable or graft form. The matrix graft is used for human dermal tissue defects, while the injectable form is used as a bulking agent for patients with fecal incontinence. [28]

Other, less commonly–used fillers (noncollagen)

Aquamid  [29]

Aquamid is manufactured by Contura Internationa A/S. It is not currently approved by the FDA. [8]  It is approved in Europe and 40 other countries. [30]

Aquamid is a nonabsorbable filler that contains approximately 2.5% cross-linked polyacrylamide and 97.5% nonpyrogenic water. A more viscous version is marketed as Aquamid Reconstruction. The filler is packaged as a sterile, prefilled 1-mL syringe. Advese events were localized to reactions at the injection site. It is recommended that Aquamid be injected subcutaneously in a retrograde, fan-shaped manner. A minimum of 14 days should elapse before additional injections.

Hydrelle (formerly Elevess)  [31]

Hydrelle (formerly Elevess) is approved by the FDA and is manufactured by Anika Therapeutics, Bedford, MA. [32]

Hydrelle (previously known as Elevess) is a cross-linked hyaluronic acid and lidocaine injectable gel. The hyaluronic acid in this product is produced from Streptococcus equi. It is contraindicated in patients with a history of allergies to lidocaine, sodium metabisulfite, or gram-positive bacterial proteins. Adverse events include injection site ecchymosis and edema, as well as nodule formation, edema, contusion, and facial swelling. Hydrelle is FDA approved for injection at the mid- to deep dermal level to improve the appearance of moderate to severe facial rhytids and folds, including the nasolabial folds. [33]

Azficel-T (formerly Isolagen)

Azficel-T (LAVIV) was approved by the FDA in June 2011 and is manufactured by Fibrocell Science, Inc.

Azficel-T is prepared by harvesting autologous skin, purifying the host fibroblasts, and packaging it in a suspension for intradermal injection. A piece of skin derived from a punch biopsy from behind the ear is sent to the company. From this, the fibroblast population of cells is isolated and grown. These cells are the ones responsible for collagen synthesis in vivo. After 6 weeks, a vial of cells (~18 million fibroblasts/1.2 mL) is sent back to the physician for injection. Implantation of the material must take place before the vial expires, otherwise it is unusable. Therapy consists of a series of 3 intradermal injection sessions administered 3-6 weeks apart. The dose is 0.1 mL ID per linear centimeter into the nasolabial fold wrinkles. Only physicians who complete a Fibrocell-approved training program will be able to administer it.

This is a biological that works over time to provide gradual and natural results.

The FDA approval was based largely on 2 identical phase 3 multicenter, randomized, double-blind, placebo-controlled studies involving 421 patients who underwent 3 treatment sessions approximately 5 weeks apart. [34]

On the basis of investigators' and patients' assessments, a significantly greater proportion of patients demonstrated a positive response to treatment with azficel-T than with placebo. The treatment improved the appearance of nasolabial fold wrinkles for the 6 months of patient follow-up after the last treatment. The company said studies are ongoing, looking at how long beyond 6 months after the last treatment the effect may last.

Because the product is autologous, little risk exists of allergic response. In clinical trials, the most common adverse events were mild-to-moderate injection-site reactions that usually resolved within 1 week. Once harvested and processed, a long-term supply of fibroblasts is then available for the patient. The cells can be cryogenically stored for use years later. A theoretical benefit may also exist in using cells that were isolated from the patient at a much younger age.

Silikon 1000 and ADATO Sil-OI-Silicone Oil

Silikon 1000 is approved by the FDA for certain ophthalmologic applications but not cosmetic surgery; it is manufactured by Dow Corning, Midland, Mich. ADATO Sil-OI-Silicone Oil is approved by the FDA as an intraocular fluid; it is manufactured by Bausch & Lomb, Tampa, Fla. [8]

Medical grade silicone was originally used in the 1960s for correction of wrinkles and soft tissue defects. Its popularity led untrained practitioners to use industrial grade silicone, which resulted in many severe, well-publicized complications. In the hands of a trained practitioner, its use can yield cosmetically superior results. At present, it is not approved for cosmetic filler applications but is used for off-label indications.

Other synthetic fillers

There are several other fillers that are not approved by the FDA but are approved in other countries. [30]  Bioplastique is a silicone filler approved in Europe. [30] Several polyacrylamide fillers are approved in Europe, Asia, South America, or Canada and include Beautical, Bio-Alcamid, Outline, Evolution, Formacryl, Argiform, Bioformacryl, Amazing Gel, DermaLive/DermaDeep, Metacril, and ArteSense. [30] Other fillers available internationally include Laresse Dermal Filler (carboxymethylcellulose/polyethylene), Atléan BTCP (tricalcium phosphate), Bioinblue (polyvinyl alcohol), and Matridex (DEAE Sephadex). [30]

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Surgical Therapy

Other procedures include surgical methods of replacing or implanting material into the dermis for scar elevation.

Dermal grafting

Dermal grafting is an old technique for the treatment of larger depressed scars. The dermis is harvested, defatted, placed in saline, and then divided into sections to fit the size of the defect. A simple access incision is made to create a pocket within and under the scar in which the dermal implants are placed. Because this represents a graft, little absorption occurs and the results may be long-lasting.

Synthetic grafts

Similarly, synthetic grafts such as Gore-Tex and SoftForm can also be used to fill scars. These are synthetic products that are surgically placed within and under the dermis for augmentation. Gore-Tex is a polytetrafluoroethylene product that has been used extensively in cardiovascular, urologic, and reconstructive surgery. For skin augmentation, it must be placed in the superficial subcutaneous tissue. It is a technique-sensitive operation with adverse reactions including infection, foreign body extrusion, and movement of the implant from the placement site. The product is best for atrophic scars, full-thickness skin defects, and deep melolabial furrows. The implant is permanent and movement or extrusion requires replacement and surgical revision.

The use of either injectable or surgically placed implants for the correction of acne scars depends on the surgeon's and patient's desires. Many patients are satisfied with the simple but repeatable procedure of Zyderm collagen, while others insist upon a single procedure. Both of these choices are available with the advent of new injectable and implantable skin-filling substances.

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Preoperative Details

To reduce potential bruising, patients should discontinue any medications that inhibit platelet aggregation approximately 2 weeks prior to collagen or any filler augmentation. [35]

To provide adequate pain management, topical anesthetics may be applied and allowed to stand for 30 minutes. Nerve blocks to anesthetize the proposed treatment area can also be applied to alleviate the pain associated with filler injection. Injectable collagens are prepackaged with lidocaine within the syringe, obviating the need for local anesthesia. [35] Some dermal fillers are also manufactured with lidocaine.

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Intraoperative Details

The technique of filler injection is operator-dependent; however, 2 methods commonly used by physicians include serial puncture and linear threading.

Serial puncture involves injecting small amounts of collagen several times in a row to fill a fold. This method provides greater precision but at the expense of multiple entry sites.

In linear threading, an injection is used only once and fills the fold with collagen in a linear fashion. Although this technique allows for a better outline of the wrinkle, the inability to see while injecting the collagen carries a greater risk of vascular accidents. [8]

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Postoperative Details

Cooling the area after the procedure reduces inflammation around the injection site. The patient may resume daily activities soon thereafter.

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Complications

Complications include bruising, purpura, lumpiness, delayed mediated hypersensitivity reaction with granuloma formation, vascular infarction with tissue necrosis, and cystic ulceration.

A study by Goodman et al indicated that even those with experience in dermal filler injections can mistakenly administer intravascular injections, finding that 62% of the study’s 52 survey respondents (from 16 countries) reported at least one intravascular injection; 71% of the 52 respondents had at least 11 years’ experience administering injections. Immediately following diagnosis of intravascular injection, hyaluronidase was used to treat the problem in 86% of cases. Most patients experienced uneventful healing. [36]

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Outcome and Prognosis

Collagen is an excellent temporary skin filler that yields a natural cosmetic result. After 1 or 2 treatments, the patient's defect should be stable and the correction should last 6-9 months.

See the photos below.

Photograph before collagen injection. Photograph before collagen injection.
Photograph after collagen injection. Photograph after collagen injection.
Photograph before collagen injection. Photograph before collagen injection.
Photograph after collagen injection. Photograph after collagen injection.
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Future and Controversies

Some questions remain concerning prion activity among the bovine herds and possible "mad cow disease" infection from collagen injections. However, this is hypothetical and care has been taken to isolate the Zyderm bovine herd from other cattle to prevent such an occurrence.

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