US Pharm. 2019;44(10):9-12.

Today, people live longer and are healthier as a result of improvements in modern healthcare, and they can now improve their appearances noninvasively and without surgery. This is in part because developments in medical science have spurred a series of new products, such as dermal fillers. The demand for dermal fillers and the variety of dermal fillers have increased dramatically during the past couple of decades. As a result, soft-tissue fillers are increasingly important as nonsurgical treatment options for facial rejuvenation.¹

Dermal fillers are used for cosmetic purposes and are meant to give volume and fullness to an individual’s skin. When used properly, these products diminish the most common signs of aging such as facial wrinkles and skin folds. Most women use these products to make themselves look younger.²

Dermal fillers are found in many forms. The benefits and risks vary from one product to the next, and the risks can be diminished by using professional injections and sterile instruments. After injection, skin should be protected with sunscreen bases to limit the risk of postinflammatory pigment changes. Cost is also an important factor: Less costly products tend to come with more risks than the highest cost alternatives.^1,2 In this article, we briefly review the FDA-approved products, their applications, and associated risks and benefits.

Skin Structure

The skin is the largest organ of the body, with a total area of about 20 square feet. It is formed of three layers: The uppermost layer is known as epidermis, followed by dermis, and then hypodermis (subcutaneous tissue). The epidermis controls the loss of water from cells and tissue. Without this protective barrier, the body would quickly dehydrate.

Just below the epidermis lies the second layer, the dermis. The dermis, although it contains blood vessels, nerves, and hair follicles, is primarily made up of a protein called collagen. Collagen forms a network of fibers that provides a matrix for the growth of cells and blood vessels. Because it is the primary component of the dermis, collagen acts as the support structure for the skin.

The hypodermis is a layer of fat and connective tissue that contains larger blood vessels and nerves as well as sweat glands, fat, and collagen cells. The hypodermis conserves the body’s heat and protects vital organs.

FDA-Approved Facial Fillers

Cosmetic surgeons employ a variety of FDA-approved fillers. These fillers are categorized as medical devices by the FDA and are safe when applied by a board-certified cosmetic surgeon.

Bovine Collagen

Bovine collagen was the first material approved by the FDA for injection into facial scars, furrows, and lines. Bovine collagen (95% type I and 5% type III collagen) was approved in 1981; buffered collagen was FDA approved and released shortly thereafter.^3,4

Skin tests are required before injecting bovine-collagen products. This is due to reports that flulike symptoms, paresthesias, and severe anaphylactic shock have been seen after injection of bovine collagen, limiting the popularity of bovine collagen’s usage as skin filler. As a result, human-derived bioengineered collagen implants were developed to lessen the chance of hypersensitivity reaction.⁴ No skin test for hypersensitive reactions is required with these products.

Hyaluronic Acid

Hyaluronic acid (HA) is a natural substance in the skin used to keep it hydrated. HA fillers are soft gels, and their effects last 6 to 12 months or longer before the body gradually absorbs them. Most HA fillers are infused with lidocaine to minimize pain during and after treatment.⁵

Sodium salt of HA (sodium hyaluronate) is a biological polysaccharide that is distributed widely in the extracellular matrix of connective tissues. It forms a viscoelastic solution in water, and its intradermal injection may decrease the depth of facial wrinkles.⁶

Formulations of this product differ in terms of recommended injection depth. A typical treatment regimen requires 1.6 to 1.7 mL/treatment site. For hand augmentation in adults older than age 21 years, small boluses up to 3 mL are injected in the subcutaneous dorsum of the hand per treatment session. For lip augmentation, approximately 2.2 mL are injected into the lips and perioral area. This will correct up to 100% of the desired volume effect. Repeat treatment is generally 1.5 mL.⁷

Calcium Hydroxylapatite

Calcium hydroxylapatite (CaHA) is a natural substance found primarily in our bones. The calcium particles are microspheres and are suspended in an aqueous carboxymethylcellulose gel carrier. This occurs soon after injection and is a result of accumulated particles and not a granulomatous reaction.⁸ Its consistency is thicker than that of HA, and it lasts longer, up to 12 months. This product is considered a long-lasting but nonpermanent filler and is highly biocompatible with human tissues. No osteogenesis has been reported with the use of CaHA in a variety of soft-tissue applications. CaHA reportedly stimulates natural collagen production and is used for deeper lines and wrinkles.⁹

Clinical trials that have followed patients for up to 3 years postinjection report no long-term or delayed-onset adverse events.

Poly-L-Lactic Acid

Poly-L-lactic acid (PLLA) is a biocompatible, biodegradable synthetic polymer. It has been used for many years in medicine in stitches. All of its products are classified as collagen stimulants. The gel itself dissipates a few days after treatment, and it is used to treat deeper facial wrinkles, the results lasting for up to 2 years. These polymers provide long-term to permanent correction of facial deficits. All are injected into the skin and mechanically “bulk” the skin out. PLLA is widely used as filler in facial-volume restoration.¹⁰

Polymethylmethacrylate

Polymethylmethacrylate (PMMA) is considered a semipermanent filler, and it is most often used to treat medium-to-deep wrinkles, folds, and furrows, in particular nasolabial folds (smile lines). It is a synthetic, biocompatible, rigid, transparent, and thermoplastic material. It is used in contact lenses. As a dermal filler, PMMA takes the form of a microsphere or tiny balls and remains under the skin indefinitely to provide continued support to the face.¹¹

PMMA fillers also contain collagen, which provides structure and firmness. Given the bovine collagen component, a skin test must be performed at least 2 to 4 weeks before any injection with PMMA products. As mentioned above, this test is done in order to detect an allergy to the bovine collagen component. This product was recently approved by FDA to improve the appearance of facial acne scars on the cheeks. This makes it the only FDA-approved injectable filler for acne scars. The effect of PMMA can last up to 5 years.¹²

PMMA injections to the periocular region may be associated with giant-cell inflammation, yellowing of the skin, and eyelid malposition. Corticosteroid injection may have limited efficacy and may be beneficial.¹²

Facial Fillers‘ Adverse Reactions

According to the American Academy of Dermatology, redness, swelling, pain, bruising, itching, and rash can occur around injection sites, but these usually clear within 7 to 14 days. In addition, there are rare side effects such as infection, leakage of the filler through the injection site, nodules around the injection site, granulomas, movement of the filler under the skin, and blood vessel injury. All or some of these side effects will be minimized if the procedure is performed by an experienced cosmetic professional.^13,14

Facial Fat Grafting

Personal fat injections (autologous) are the only injectable filler treatments that require surgery, but the outcome can last for many years. The person’s fat is harvested from another area using liposuction. This fat is then purified and injected into the face to support cheeks, lower eyelids, temples, and other areas. This treatment requires special skills and must be performed by an experienced board-certified cosmetic surgeon. This procedure follows a different treatment protocol and is normally done as an outpatient procedure, using general or local anesthesia with sedation. The recovery may take up to 2 weeks.¹⁵

Facial Treatment

A facial treatment with dermal fillers takes a few hours in the office. It begins with a consultation about the patient’s concern and goals. The surgeon evaluates the area of concern and reviews the patient’s medical history. While risks associated with a procedure are minimal, certain allergies, skin neurological conditions, or medications can affect results. As an example, if a patient is taking nonsteroidal anti-inflammatory drugs or blood thinners, bruising is possible.

Normally, before the procedure, the area will be cleaned and numbed. A precise amount of the filler will then be injected beneath the skin. Depending on the area treated and the product, patients will see the results immediately. Any kind of bruising and swelling will go away over several days. People can usually begin their normal activities right after treatment.

REFERENCES

1. Carruthers J, Carruthers A, Humphrey S. Introduction to fillers. Plast Reconstr Surg. 2015;136(Suppl 5):S120-131.
2. Homicz MR, Watson D. Review of injectable materials for soft tissue augmentation. Facial Plast Surg. 2004;20(1):21-29.
3. Cockerham K, Hsu VJ. Collagen-based dermal fillers: past, present, future. Facial Plast Surg. 2009;25(2):106-113.
4. Douglas RS, Donsoff I, Cook T, et al. Collagen fillers in facial aesthetic surgery. Facial Plast Surg. 2004;20:117-123.
5. Weinkle S. Injection techniques for revolumization of the perioral region with hyaluronic acid. J Drugs Dermatol. 2010;9(4):367-371.
6. Mansouri Y, Goldenberg G. Update on hyaluronic acid fillers for facial rejuvenation. Cutis. 2015;96:85-88.
7. Raspaldo H, De Boulle K, Levy PM. Longevity of effects of hyaluronic acid plus lidocaine facial filler. J Cosmet Dermatol. 2010;9(1):11-15.
8. Pavicic T. Calcium hydroxylapatite filler: an overview of safety and tolerability. J Drugs Dermatol. 2013;12(9):996-1002.
9. Ahn MS. Calcium hydroxylapatite: radiesse. Facial Plast Surg Clin North Am. 2007;15:85-90.
10. Ralston JP, Blume JE, Zeitouni NC. Treatment of postoperative soft tissue loss with injectable poly-L-lactic acid (PLLA). J Drugs Dermatol. 2006;5(10):1000-1001.
11. Limongi RM, Tao J, Borba A, et al. Complications and management of polymethylmethacrylate (PMMA) injections to the midface. Aesthet Surg J. 2016;36:132-135.
12. Von Buelow S, Von Heimburg D, Pallua N. Efficacy and safety of polyacrylamide hydrogel for facial soft-tissue augmentation. Plast Reconstr Surg. 2005;116:1137-1146.
13. Hirsch RJ, Stier M. Complications of soft tissue augmentation. J Drugs Dermatol. 2008;7(9):841-852.   
14. Requena L, Requena C, Christensen L, et al. Adverse reactions to injectable soft tissue fillers. J Am Acad Dermatol. 2011;64:1-34.
15. Kanchwala SK, Bucky LP. Facial fat grafting: the search for predictable results. Facial Plast Surg. 2003;19:137-146.

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