Injection Facial Fillers

In the early 1970s, bovine collagen became the first injectable filler used to augment the face. A multitude of products have since been developed for soft tissue augmentation. ^[1]  According to The Aesthetic Society, 649,176 filler procedures were performed in the United States in 2022, making it the third most common nonsurgical aesthetic procedure that year. The figure was a 13% increase over the 2021 count but approximately 31% lower than the number from 2019 (945,164), prior to the coronavirus disease 2019 (COVID-19) pandemic. ^[2]  In 2022, among nonsurgical aesthetic procedures worldwide, hyaluronic acid filler procedures were the second most common, at 4.3 million, with botulinum toxin procedures being the most frequent. However, the hyaluronic acid figure was down from the almost 5.3 million procedures in 2021. ^[3]

Broadly, facial fillers can be divided into four categories: autologous fat, collagens, hyaluronic acid, and synthetic fillers. This article discusses the injection of soft tissue fillers into two distinct skin depths: subdermal (as performed with synthetic calcium hydroxylapatite) and intradermal (as performed with hyaluronic acid). Though incredibly useful and with some major advantages, autologous fat is not described further in this article. ^[4]

Elastic modulus (G’)

G’ is a descriptor used in signifying the firmness of a gel. It indicates the ability of a gel to resist deformation when acted on by a force; in simpler terms, it provides a quantitative measure for characterizing how hard or soft a gel is. The G’ depends on the gel's degree of molecular cross-linking and concentration; manufacturers can manipulate these variables to influence the firmness or softness of their fillers. ^[5] Products with higher G’ are generally better able to resist dynamic forces (such as those that occur with facial movement), offer more volume and support, and require deeper placement. Lower G’ products are more suitable for areas of the face where resistance to deformation is not critical (for instance, static or superficial wrinkles) and in locations where softness is important. The G’ of the human dermis is in the range of 3 MPa, which means that even hyaluronic acid fillers with the highest G’ are still softer than the dermis. ^{[6, 7, 8, 9, 10]}

Injectable soft tissue fillers are indicated for wrinkles, folds, and lines associated with aging. Areas commonly addressed in the face include the forehead, glabella, nasolabial folds, and lips. ^[11] Certain fillers are also used for contour deformities associated with acne scarring or HIV-associated lipoatrophy. Practitioners have developed many off-label uses for each product. ^[12] ​

A study by Occhiogrosso et al indicated that in patients with facial paralysis, dermal filler treatment improves not only facial symmetry, but also psychosocial well-being. As measured using the FACE-Q Appearance-related Distress Screening Scale, a particular increase was found in self-confidence and emotional expression, with improvements in symmetry (self-reported) and psychosocial state being achieved after a single treatment of, on average, 2.3 mL of dermal filler, as seen at 2-week follow-up. ^[13]

Some commonly used fillers and their properties are listed below. ^{[14, 15, 16, 17]}

Hyaluronic acid fillers

Hylaform (Genzyme)

See the list below:

• Material: Hyaluronic acid derived from dermis of rooster combs; concentration 5.5 mg/mL; 500-µm particles; 20% cross-linked

• How supplied: Disposable glass syringe, 30-gauge (ga) needle

• Skin testing required: No

• Duration: 3-6 months

• Depth of injection: Mid- to deep dermis

• US Food and Drug Administration (FDA) indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytides and volume augmentation at other body sites

• Contraindications: Hypersensitivity to avian proteins

Restylane (Galderma)

See the list below:

• Material: Hyaluronic acid derived from Streptococcus equi, chemically cross-linked with butanediol diglycidyl ether (BDDE), stabilized and suspended in phosphate-buffered saline at pH 7 and concentration 20 mg/mL; nonanimal stabilized hyaluronic acid (NASHA); 400 µm gel particles; 1% cross-linked; Restylane-L/Kysse/Lyft/Silk contain 0.3% lidocaine

• How supplied: Disposable glass syringe with Luer-Lok fitting, 30-ga needle

• Skin testing required: No

• Duration: 6 months (Defyne lasts up to 12 months)

• Depth of injection: Mid- to deep dermis

• FDA indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds in adults over age 21 years; Kysse and Silk are marketed for lip augmentation

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytides and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, bleeding disorders

Perlane/Perlane-L (Galderma)

See the list below:

• Material: Hyaluronic acid derived from S equi, chemically cross-linked with BDDE, stabilized and suspended in phosphate-buffered saline at pH 7 and concentration 20 mg/mL; NASHA; 940-1090 µm gel particles. Perlane-L contains 0.3% lidocaine

• How supplied: Disposable glass syringe with Luer-Lok fitting, 27-ga needle

• Skin testing required: No

• Duration: 6-12 months

• Depth of injection: Deep dermis to superficial subcutis

• FDA indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, bleeding disorders

Juvéderm (Allergan)

See the list below:

• Material: Hyaluronic acid derived from S equi cross-linked with BDDE in homogenized gel; concentration ranges from 24-30 mg/mL; all XC products contain lidocaine; Volbella/Vollure manufactured using Vycross^® technology

• How supplied: Suspended in physiologic buffer; two 1.0-mL syringes (except Volbella, which comes with 0.55 mL syringes) with 27- or 30-ga needles

• Skin testing required: No

• Duration: Ultra Plus/Ultra/Volbella - up to 1 year; Voluma - up to 24 months; Vollure - up to 18 months

• Depth of injection: Mid- to deep dermis; Voluma can be subcutaneous and/or subperiosteal

• FDA indications: Vollure/Ultra/Ultra Plus indicated, in adults over age 21 years, as a filler for moderate to severe facial wrinkles and folds (such as nasolabial folds); Voluma is indicated for deep injection in the cheek area to correct age-related volume loss in adults older than 21 years; Volbella is indicated for lip augmentation and as a means of filling in perioral lines, in adults over age 21 years

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins or to lidocaine

Prevelle Silk (Mentor)

See the list below:

• Material: Hyaluronic acid derived from S equi; homogenized gel

• How supplied: Hyaluronic acid gel cross-linked with 0.3% lidocaine; syringe contains 0.9 mL with Luer-Lok adaptor, two 30-ga needles

• Skin testing required: No

• Duration: 2-3 months

• Depth of injection: Mid- to deep dermis

• FDA indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytides and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, lidocaine hypersensitivity

Belotero Balance (Merz)

See the list below:

• Material: Hyaluronic acid derived from S equi; homogenized gel

• How supplied: A monophasic hyaluronic acid gel that contains variability of cross-linkage; thought to decrease risk of Tyndall effect; syringe contains 0.9 mL with Luer-Lok adaptor, two 30-ga needles

• Skin testing required: No

• Duration: 6 months

• Depth of injection: Superficial to mid dermis

• FDA indications: Moderate to severe facial wrinkles and folds

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, lidocaine hypersensitivity

Elevess (Anika)

See the list below:

• Material: Hyaluronic acid gel cross-linked with p-phenylene bisethyl carbodiimide (BCDI); concentration 28 mg/mL; contains 0.3% lidocaine

• How supplied: Pre-filled, glass 1-mL syringe; two 30-ga, half-inch needles

• Skin testing required: No

• Duration: 6 months

• Depth of injection: Mid- to deep dermis

• FDA indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, lidocaine hypersensitivity

Teosyal (Teoxane)

See the list below:

• Material: Monophasic, non-animal hyaluronic acid, cross-linked with BDDE; concentration 15-25 mg/mL

• How supplied: Two 1-mL syringes with 27- or 30-ga needles

• Skin testing required: No

• Duration: 6-24 months

• Depth of injection: Mid- to deep dermis

• FDA indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds, in adults aged 22 years or older

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, lidocaine hypersensitivity

Revanesse Versa (Prollenium)

See the list below:

• Material: Hyaluronic acid derived from streptococci; concentration 22-28 mg/mL

• How supplied: Two 1-mL glass syringes, two sterile needles

• Skin testing required: No

• Duration: 12 months

• Depth of injection: Mid- to deep dermis

• FDA indications: Moderate to severe facial wrinkles and folds, such as nasolabial folds, in adults aged 22 years or older

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, lidocaine hypersensitivity

Esthélis (Anteis)

See the list below:

• Material: A monophasic hyaluronic acid gel created with cohesive polydensified matrix (CPM) technology, which produces two different density levels in a single product; concentrations are 20 mg/mL for Esthélis Soft and 22.5 mg/mL for Esthélis Basic

• How supplied: Comes in either 0.6-mL or 1-mL volumes. The Soft product comes with two 30-ga, half-inch needles; the Basic product comes with one 30-ga and one 27-ga, half-inch needle

• Skin testing required: No

• Duration: 6-18 months

• Depth of injection: Superficial to mid-dermis

• FDA indications: Not yet FDA approved in the United States

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytids and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, allergies to gram-positive bacteria proteins, lidocaine hypersensitivity

Non–hyaluronic acid fillers

Radiesse (Merz)

• Material: Calcium hydroxylapatite microspheres (25-45 µm) suspended in a gel carrier of sterile water, glycerin, and sodium carboxymethylcellulose

• How supplied: 1-mL syringe

• Skin testing required: No

• Duration: 1-2 years

• Depth of injection: Subdermal

• FDA indications: HIV-associated lipoatrophy, moderate to severe facial wrinkles and folds (eg, nasolabial folds)

• Off-label uses: Marionette lines, glabella folds, prejowl sulcus, cheek volume loss, dorsal nasal deformities, lip augmentation

• Contraindications: Severe allergies manifested by history of anaphylaxis or history or presence of multiple severe allergies; hypersensitivity to any of the components

Sculptra (Galderma)

See the list below:

• Material: Poly-L-lactic acid mixed with mannitol and sodium carboxymethylcellulose

• How supplied: Reconstituted with 5 mL sterile water and lidocaine solution to form hydrocolloid suspension; supplied as freeze-dried preparation for injection in a clear glass vial

• Skin testing required: No

• Duration: 2 years

• Depth of injection: Subdermal

• FDA indications: HIV-associated lipoatrophy

• Off-label uses: Cosmetic use

• Contraindications: Hypersensitivity to any of the components

Bellafill (formerly, ArteFill) (Suneva Medical)

See the list below:

• Material: Polymethylmethacrylate microspheres (30-50 µm)

• How supplied: Suspended in water-based carrier gel composed of 3.5% bovine collagen, 92.6% buffer isotonic water for injection, 0.3% lidocaine, 2.7% phosphate buffer, and 0.9% sodium chloride

• Skin testing required: Yes

• Duration: Some degree of permanence

• Depth of injection: Subdermal

• FDA indications: Correction of nasolabial folds and treatment of acne scars ^[18]

• Off-label uses: Deep wrinkles at other sites on the face, soft tissue contour deficiencies or deformities

• Contraindications: Positive response to required Bellafill skin test, severe allergies manifested by history of anaphylaxis or history or presence of multiple severe allergies, lidocaine hypersensitivity, allergy to any bovine collagen products, undergoing or planning to undergo desensitization injection to meat products, use in lip augmentation and injection into the vermillion or the wet mucosa of the lip, known susceptibility to keloid formation or hypertrophic scarring

Zyderm I (DISCONTINUED, added here for historical perspective only)

• Material: Highly purified bovine dermal collagen (95% type I collagen, 5% type III collagen); concentration 35 mg/mL

• How supplied: Dispersed in a phosphate-buffered physiological saline containing 0.3% lidocaine

• Skin testing required: No

• Duration: 2-4 months

• Depth of injection: Superficial dermis

• FDA indications: Correction of contour deformities of the dermis in non–weight bearing areas

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytides and volume augmentation at other body sites

• Contraindications: Hypersensitivity to bovine collagen, lidocaine hypersensitivity, autoimmune disease, anaphylactoid reactions, immunosuppressive therapy, chronic inflammatory disease, active inflammation or infection at injection site

Cosmoderm I (DISCONTINUED, added here for historical perspective only)

• Material: Highly purified human-based collagen; concentration 35 mg/mL

• How supplied: Dispersed in phosphate-buffered physiologic saline containing 0.3% lidocaine

• Skin testing required: No

• Duration: 3-4 months

• Depth of injection: Superficial dermis

• FDA indications: Soft tissue contour deficiencies such as wrinkles and acne scars

• Off-label uses: Correction of age-, surgery-, and disease-related facial depressions and rhytides and volume augmentation at other body sites

• Contraindications: Severe allergies manifested by history of anaphylaxis, lidocaine hypersensitivity

General contraindications include a history of severe allergy or anaphylaxis, bleeding disorders, and hypersensitivity to one of the components in the product preparation. For example, the use of Hylaform is contraindicated in patients with allergic reaction to avian products or eggs, and anyone with a sensitivity to gram-positive bacteria proteins should not undergo injection with those hyaluronic acid products derived from bacterial fermentation. A skin test must be performed prior to injection of fillers derived from bovine sources (bovine collagen and Bellafill).

Other relative contraindications include recent use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or herbal supplements known to affect coagulation and hemostasis (see drug list in Indications section above for more details).

A number of options are available for providing anesthesia when injecting soft tissue fillers. Many practitioners use a combination of different agents, including ice, topical numbing cream, local anesthetic injection, and local anesthetic for regional nerve blocks.

Perhaps the greatest anesthetic effect is achieved by putting the patient's mind at ease. A softly lit room with soothing background music and a comfortable chair helps to provide a tranquil and relaxed experience. In fact, music has been shown to increase the level of sedation in patients undergoing surgical procedures. ^{[19, 20]} Distraction techniques such as talking or vibration devices are also very helpful. Vibrational distraction has been demonstrated to enhance comfort during dermatologic procedures. ^[21]

Anesthesia for procedure

Apply a topical numbing cream to the areas to be injected and occlude with Tegaderm. Wait at least 30 minutes for this to infiltrate the skin.

Next, lightly spray the gingivolabial sulcus of the upper lip with Cetacaine to dull the sensation of the lip in preparation for the infraorbital block. An infraorbital block is preferred to direct soft tissue infiltration, as the latter distorts the tissues to be augmented.

For the infraorbital block, a 1:1 mixture of lidocaine 1% with 1:100,000 epinephrine and bupivacaine 0.5% with 1:200,000 epinephrine provides long-term anesthesia with a rapid onset. Insert the needle through the upper gingivolabial sulcus and advance the tip up the face of the maxilla and into the infraorbital foramen. The infraorbital foramen is found within 1 cm inferior to the infraorbital rim in the midpupillary line. ^[22] Inject approximately 1 mL of the local mixture.

For more details on this anesthetic procedure, see the Medscape Drugs & Diseases article Infraorbital Nerve Block.

Equipment for filler procedures includes the following:

• Nonsterile preparatory stand

• Ice cubes in a cup

• Isopropyl alcohol pads

• Topical anesthetic cream (eutectic mixture of local anesthetics [EMLA], LMX-4, liposomal lidocaine)

• Tegaderm

• Cetacaine spray (14% benzocaine, 2% butamben, 2% tetracaine)

• Lidocaine 1% with 1:100,000 epinephrine

• Bupivacaine 0.5% with 1:200,000 epinephrine

• 3-ring control syringe, 10 mL

• 27- and 30-ga needles (often included in injectable filler kit)

• Marking pen

• Vibrational distracting device

• Soft tissue filler of choice

The patient should be in a relaxed and generally supine position. Most importantly, the patient should be comfortable. It can be advantageous to elevate the head as much as possible in order to evaluate the injection from an upright position.

After having a frank conversation about the treatment areas, expected results and the potential risks, provide anesthesia as described above in the Anesthesia section.

After the topical anesthetic has had time to work, the clinic nurse should remove the topical cream and cleanse the skin thoroughly with isopropyl alcohol pads.

If any question remains about the areas that are of most concern for the patient, mark them with a surgical marking pen as the patient looks in a mirror.

Prepare the filler. The choice of needle is determined by the viscosity of the filler; the smallest needle that can deliver the filler is the best choice. ^[23] For injection of hydroxylapatite into the nasolabial folds, the author prefers a 27-ga, 1.25-inch needle.

Filler can be injected by one of the following 4 techniques: serial puncture, threading, fanning, and crosshatching. ^{[24, 25]} Each technique has advantages for certain situations, and the ultimate determining factor is often surgeon preference.

• Serial puncture involves injecting a series of small boluses of the filler along the length of the defect.

• Threading involves tunneling the needle beneath the defect at the appropriate depth and injecting the product as the needle is withdrawn (linear threading). When combined with serial puncture, the technique is called serial threading. The threading technique is commonly used for lip and nasolabial fold augmentation.

• Fanning is similar to threading, but multiple threads are injected radially by changing direction without withdrawing the needle. The author finds that this technique works quite well for augmentation of the nasolabial folds.

• Crosshatching involves injection of a series of threads perpendicular to one another in a grid. Both fanning and crosshatching techniques are used to fill larger defects and for facial shaping. Prior to inserting the needle, treat the site with an ice cube for 30 seconds.

The angle of injection is determined by the depth of the defect. Fine to moderate rhytides and other superficial defects require injection into the mid-dermis with an angle of approach of 30-45 degrees. Deeper rhytides may require an entry angle of greater than 45 degrees. ^[23] For injection of calcium hydroxylapatite, the target depth for augmentation is the dermal-subdermal junction.

The orientation of the needle bevel does not significantly affect results. ^[26] However, the author prefers to position the bevel away from the epidermis to prevent too superficial injection into the dermis, which is more problematic than too deep injection.

When injecting in the subdermis, slightly overcorrecting the defect by perhaps 5% is wise. This takes into account the immediate swelling that occurs by advancing the needle through the tissues.

When the defect has been adequately augmented, the product is then firmly massaged into place. This most important step evenly distributes the filler and helps to smooth and customize the product to the contour of the augmented tissues.

The video below demonstrates the procedure, including preprocedure anesthesia, the fanning and crosshatching injection techniques, and massaging the product into place.

 

A study by Libby et al suggested that prior to injection, 35% of dermatologists mix hyaluronic acid or calcium hydroxylapatite fillers with another substance, such as plain lidocaine (44%), lidocaine with epinephrine (36%), normal saline (30%), or sterile water (7%). The study, in which 475 members of the American Society for Dermatologic Surgery were surveyed, found that 40% of the respondents engaged in the practice to decrease the filler’s viscosity. Mixing was also performed to increase anesthesia (30%), decrease swelling (17%), or increase volume (13%). ^[27]

As with every procedure, complications do occur. ^[28] Certain complications, such as pain, needle marks, bruising, and swelling, are expected in the immediate postprocedure period. Even some asymmetry associated with over or undercorrection is expected within the first 2 weeks but usually resolves without intervention. ^[26] Should overcorrection from hyaluronic acid persist, several authors have reported successfully using hyaluronidase to treat this problem. ^{[26, 29, 30]} The table below compares expected adverse effects and true complications of facial fillers.

Infections occur infrequently and are due to improper technique. They may have an immediate or delayed onset.

Immediate hypersensitivity reactions can occur with any filler but are predominantly an issue with bovine-derived fillers, with up to 3% of patients developing a sensitivity reaction even with a normal skin test. ^[31] The continued refinement of product formulations has virtually eliminated delayed hypersensitivity reactions to Restylane. ^[32]

A complication specific to hyaluronic acid is the Tyndall effect, which manifests as a blue bump under the skin due to an injection that was too superficial. This can be prevented by pointing the needle bevel away from the epithelium.

All fillers are expected to create some form of histological reaction that evolves over time. Nodules and granulomas can form as part of an inflammatory granulomatous process and may require excision if they do not respond to steroid injections. ^[33]

Serious complications from injectable fillers have been reported and include anaphylaxis, skin necrosis, blindness, and death. ^{[25, 34, 35]} Fortunately, these complications are very rare. The glabella is believed to be at risk for skin necrosis because of small-caliber vessels that branch from the supratrochlear arteries to supply this area, ^[36] though this is controversial.

Accidental intravascular injection of facial fillers can result in skin necrosis and blindness. 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. ^[37]

Table. Adverse Effects vs Complications (Open Table in a new window)

Instruct the patient to avoid strenuous physical activity for 24 hours and then return to normal activities. As always, the patient should avoid excessive sun exposure and should use a moisturizer with a sun protection factor (SPF) of 30 or greater.

Instruct the patient to use acetaminophen as directed on the bottle for pain relief; prescription pain medication is unnecessary. All patient medications can be resumed the night of the procedure. Encourage cold compresses to control pain, swelling, and bruising.

Tell patients to avoid massaging or manipulating the treated areas for at least 24 hours as this can disturb the position of the filler.

For the first 48 hours, use cold treatments only. However, after 48 hours, if bruising should occur, advise the patient to use warm, moist compresses, such as a moist washcloth that has been placed in a microwave for 5-10 seconds. Some patients have used black tea bags to hasten bruise healing, to take advantage, theoretically, of an antioxidant effect.