Injectable Fillers Treatment & Management

Updated: Jul 14, 2022
  • Author: Deborah Yu, MD; Chief Editor: James Neal Long, MD, FACS  more...
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Treatment

Medical Therapy

Numerous fillers are available. Each of these preparations has special properties, indications, and contraindications. Biodegradable fillers include collagen, autologous fibroblasts, hyaluronic acid, calcium hydroxylapatite, and poly-L-lactic acid. [2, 4]  Nonbiodegradable fillers include silicone (off-label) and polymethylmethacrylate beads. [4]

Fillers are used to fill defects within the skin and subcutaneous tissue, and he depth of the defect should determine the filler chosen. 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. [6]  Other noncollagen fillers include fat, calcium hydroxylapatite, and poly-L-lactic acid.

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. [7]

Hyaluronic acid

Examples of hyaluronic acid fillers include the following.

Belotero Balance is a hyaluronic-based dermal filler that is derived from streptococcal cultures and is 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-dermis to deep dermis. [8, 9]

Juvéderm is a gel containing cross-linked hyaluronic acid produced from Streptococcus equi bacteria. [10, 11, 12, 13] Different Juvéderm products have different applications, including for correction of moderate to severe facial rhytids and depressions (nasolabial folds), [13]  lip augmentation, [13] and the correction of fine perioral rhytids. [10]

To help reduce discomfort during and after treatment, the majority of hyaluronic acid fillers contain an infusion of lidocaine. [14]

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 injected nasolabial folds, with correction existing in 81% of them for 1 year or more. [15]  Subsequent treatment required a decrease in the volume of Juvéderm.

Postmarket safety surveillance of Juvéderm injectable gel in countries outside the United States found swelling, redness, discoloration, and bruising to be the most common adverse events. [16]

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.

Other common fillers

Radiesse is an aqueous gel that contains microspheres of calcium hydroxylapatite. Hydroxylapatite has a much slower rate of resorption by the body and therefore 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. Radiesse and Radiesse (+) are injected at the subdermal level to improve the appearance of severe facial rhytids and folds, such as the nasolabial folds. [17]  Radiesse is also used to correct lipodystrophy in patients with human immunodeficiency virus (HIV) as well as to address volume loss in the dorsum of the hand. [18, 19, 20]

Sculptra is an injectable filler that is composed of poly-L-lactic acid. [21]  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. [22]  Sculptra Aesthetic, which also consists of poly-L-lactic acid, is used in facial wrinkles and nasolabial folds. [23]

Collagen fillers

Collagen fillers can be divided into those of bovine, porcine, 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. Employment of collagen fillers has declined with the increased use of products such as hyaluronic acids and poly-L-lactic acid. [24]

The examples below illustrate the different types of collagen used.

AlloDerm and Cymetra (human collagen)

AlloDerm is an acellular human dermal graft processed from tissue bank–derived skin. 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.

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.

Cymetra is a micronized form of AlloDerm that is injectable. Results last in the range of 3-6 months.

LAVIV (fibroblasts/human collagen)

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. Because the product is autologous, little risk exists for an allergic response.

Bellafill (bovine collagen)

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. [25] In 2015, the FDA approved Bellafill’s use in the treatment of acne scars. It is also indicated for nasolabial fold correction. [26, 23]

Evolence Collagen Filler (porcine collagen)

Evolence Collagen Filler, derived from porcine collagen, is injected to manage moderate to deep facial wrinkles and folds. [23]

Silicone

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, silicone can yield cosmetically superior results. At present, it is not approved for cosmetic filler applications but is used for off-label indications.

Unapproved synthetic fillers

There are several fillers that have not received FDA approval but have been approved in other countries. [27]  As stated above, injectable silicone dermal filler is not approved for aesthetic use in the United States, but it is approved for it in Europe. [27, 28] Several polyacrylamide fillers are approved in Europe, Asia, the Middle East, Latin America, and Canada. [27] Other fillers available internationally include Laresse Dermal Filler (carboxymethylcellulose/polyethylene), Atléan BTCP (tricalcium phosphate), Bioinblue (polyvinyl alcohol), and Matridex (hyaluronic acid/dextranomer particles). [27]

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Surgical Therapy

Other procedures include surgical methods for 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

Synthetic grafts such as Gore-Tex and SoftForm can also be used to fill scars. These 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. The required surgery is technique sensitive, and adverse reactions, including infection, foreign body extrusion, and movement of the implant from the placement site, can occur. 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. Both of these options 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 augmentation with collagen or any other filler. [29]

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. [29] Some dermal fillers are also manufactured with lidocaine.

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Intraoperative Details

The technique of filler injection is operator dependent; however, two methods commonly used by physicians are 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 for vascular accidents. [9]

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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. [30, 31]

A study by Goodman et al indicated that even individuals 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. [32]

A literature review by Kokoska et al indicated that with regard to injections of hyaluronic acid dermal fillers, the incidence of delayed-onset reactions (>30 days post injection) depends on the type of filler used. Out of 15 hyaluronic acid fillers, the investigators found the highest risk for such reactions (mean incidence 3.83%) to be associated with VYC-15L, with the next highest associated with VYC-20L (0.92%) and VYC-17.5L (0.88%). The mean incidence of delayed-onset reactions for hyaluronic acid fillers overall was 1.13%. [33]

A retrospective study by Kern et al indicated that patients who undergo injectable filler treatments performed by qualified clinicians only rarely suffer serious adverse events. Out of 7659 individuals in the study who underwent filler injections, as administered by board-certified dermatologists, the investigators identified only four such events, including three instances of delayed-onset skin nodule formation and one instance of vascular compromise followed by cutaneous necrosis. A total of 18,013 mL of filler was administered to the patient group, with hyaluronic acid derivatives making up 74.1% of this volume, and poly-L-lactic acid and calcium hydroxylapatite making up 19.19% and 6.71%, respectively. [34]

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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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