Soft-tissue Augmentation

Introduction

As people live longer and healthier lives, more seek physicians to help them maintain and restore a more youthful appearance. A large component of the skin's natural aging process is manifest by volume loss with contour changes and rhytides secondary to atrophy of soft tissues, including both muscle and subcutaneous fat and loss of skin resistance as dermal collagen, hyaluronic acid, and elastin are depleted. Smooth, symmetric facial contours may become disrupted by natural disease, such as acne; environmental causes, such as sun exposure; trauma; or the process of aging. Scars caused by acne or trauma leave depressions of various depths, which can be improved using soft-tissue fillers. Atrophy of an entire cosmetic subunit may be caused by diseases such as HIV lipodystrophy or morphea. Fine rhytides, particularly perioral and periocular lines, can be caused by excessive actinic damage. Normal lines of facial expression become accentuated with age.

Restoration of facial symmetry and volume, as well as a smooth contour and homogeneous skin tone, are the goals of the dermatologic surgeon. A multitude of minimally invasive procedures, of which soft-tissue augmentation plays a major role, produce significant rejuvenation without the risks, downtime, and expense of surgery, such as face lift or eyelid-lift procedures. The appropriate filler can restore symmetry and volume and recreate a smooth skin surface. Particularly in combination with other treatments, such as botulinum toxin and non-ablative resurfacing, fillers may provide satisfying and prolonged results.

Significant progress has been made toward the development of an ideal filler/implant, which is characterized by the following properties: safety, efficacy, reproducibility, high use potential, non-carcinogenicity, non-teratogenicity, non-migratory, cost-effective, physiologic, semipermanent, and approved for use by US government agencies. Injectable soft-tissue augmentation materials available for use in the USA have proliferated during the past 10 years. Physicians can now choose between numerous other options, including hyaluronic acid derivatives, poly-L-lactic acid (PLLA), injectable calcium hydroxylapatite, and polymethylmethacrylate (PMMA) microspheres. While these materials are generally safe and versatile, each has specific features that govern its best use, which is discussed in detail in this chapter.

Historical Aspects

The search for an ideal soft-tissue filler for the correction of facial lines and wrinkles has spanned a century. The first organic injectable filler was injectable paraffin, first used at the turn of the twentieth century. This material, which was characterized by the appearance of paraffinomas, was abandoned. Subsequently, in the 1960s, the Dow Corning Corporation (USA) introduced a form of liquid silicone (medical grade 360) for the correction of facial deformities, lines, and wrinkles. Between 1960 and 1990, various forms of liquid silicone were utilized in the treatment of tens of thousands of patients. Complications were minimal with the use of the “microdroplet” technique, whereby silicone was injected in small aliquots through a fine-bore needle. Unfortunately, the lack of uniformity in silicone preparations, with the use of impure and adulterated silicones, resulted in several severe complications. These complications, as well as the lack of approval for silicone by the Food and Drug Administration (FDA), significantly limited silicone use in the USA until 2002. After the FDA approved the use of 1000 centistoke liquid silicone for intraocular injections in 2002, the off-label use of this injectable silicone oil as a permanent soft-tissue filler for facial rejuvenation increased in the USA.

In the 1970s, research into collagen production led to a bovine formulation that could be placed into a syringe and injected. Injectable bovine collagen was introduced into the market in 1981 by the Collagen Corporation (Palo Alto, CA). Bovine collagen was marketed by Inamed Aesthetics (Santa Barbara, CA) as Zyderm and Zyplast and is characterized by easy administration, and safe and effective short-term tissue augmentation. Injectable bovine collagen equivalents were also available in Japan (Kokenatelocollagen implant, Koken Co, KTD, Tokyo) and Europe (Resoplast, Rofil Medical International BV, Bredia, the Netherlands), all of which have similar indications to Zyderm and Zyplast collagen. However, the incidence of allergic responses to bovine collagen products and limited longevity have fueled the continual search for a more ideal dermal filler product. Human collagens analogous to Zyderm and Zyplast, namely “Cosmoderm” and “Cosmoplast” (Inamed Aesthetics), obviated the need for skin testing and largely replaced treatment with bovine collagen. All of the collagen products have fallen out of favor due to the introduction of safer fillers and are no longer widely used.

Augmentation with the patient's own dermis and fat began early in the twentieth century, with fat grafts to replace volume after trauma. However, excising and transplanting fat represented a major procedure, which in many cases did not have long-lasting effects. Neuber was the first to report use of autologous tissue for subcutaneous augmentation through the use of dermis and fat. Dermis and fat both have varying degrees of resorption after implantation, rendering unpredictable outcomes. The modern use of fat as a filling substance dates back to its reintroduction by Fournier with the “microlipoinjection” technique in the late 1970s. The longevity of contour correction after autologous fat injection is highly variable. Duration of correction is dependent on a variety of factors, including whether fat is fresh or frozen, viability of fat cells, technique utilized, amount of fat injected, location of recipient site, and type of defect treated. Recent data by Coleman suggest improved duration of correction with autologous fat transfer. Although early results with fat transfer are promising and there is an inherent intuitive benefit to using an autologous agent for soft-tissue augmentation, it is not clear that autologous fat is an ideal soft-tissue filling agent, particularly given its highly variable duration of correction. A complete discussion of fat transfer is presented in Chapter 29 .

In 1957, Spangler published his studies on the use of “fibrin foam” to treat depressed scars. Based upon this work and modifications by Gottlieb, a new product, “Fibrel”, was developed by Serono Laboratories in 1985. It was later marketed by Mentor Corporation (Goleta, CA). Fibrel is a mixture of ε-aminocaproic acid, gelatin powder, and plasma from the patient. The gelatin forms a scaffolding, upon which new collagen synthesis occurs. The enzyme inhibitor ε-aminocaproic acid blocks fibrinolysin, which decreases collagen degradation, thus increasing collagen production to fill the clot matrix. Blood plasma provides a supplemental source of fibrinogen and other clotting factors that enhance the collagen matrix. Although venipuncture and centrifugation of the patient's blood made Fibrel preparation tedious, results were generally favorable. Nonetheless, a decision was made by the Mentor Corporation to discontinue marketing of the product.

The search for an ideal, injectable, soft-tissue filler continues. A number of new products have appeared worldwide in the last two decades and new additions to the repertoire of dermal and subdermal fillers continue to grow each year. Many of the currently available injectable fillers include biologically compatible agents, such as hyaluronic acid gels (Restylane, Perlane, Juvéderm, Hylaform, Puragen), human fibroblasts (Isolagen), fascia lata (Fascian), acellular human collagen (Alloderm, Cymetra), elastin, and other human dermal products. Others have introduced substances such as Dextran (Reviderm Intra), polyethylene beads (Profill), silicone polymers (Dermagen), PMMA (Artecoll), calcium hydroxylapatite (Radiesse), or PLLA (New-Fill/Sculptra) to increase duration of correction.

Balazs and Denlinger established that insoluble, injectable, cross-linked hylan gels derived from hyaluronic acid exhibited a prolonged residence time in soft tissues and were as biocompatible as natural hyaluronan. Hylan B, first developed in the mid-1980s, is produced by introducing sulfonyl-bis-ethyl cross-links between hydroxyl groups of the polysaccharide chain of hyaluronan. Intra-articular injections of this material were found to be helpful for knee pain associated with osteoarthritis. Subsequently, it was evaluated and used for soft-tissue augmentation. Hylan B gel has a number of attributes that make it a favorable intradermal injectable implant material. It is water insoluble, resists degradation, and is unlikely to migrate. The high water content mimics the natural hydrating function of native hyaluronan in the skin. The elastic properties of the gel render it soft and natural feeling and provide elastic protection (shock absorption) to the cutaneous soft tissue. The physical properties of hyaluronic acid gels are controlled by the molecular weight and the concentration of the material and by the degree of cross-linking. The most commonly used source of hyaluronic acid are rooster combs (Hylaform), bacterial cultures (Restylane), human umbilical cord, vitreous humor, tendons, and skin.

PMMA was first synthesized in 1902 by the German chemist Rohm and was patented as Plexiglas in 1928. It has had medical applications since 1945, and is commonly used in bone cement, intraocular lenses, dental prostheses, and repair material for craniofacial surgery. In addition to being biocompatible and immunologically inert, PMMA has never demonstrated degradation or carcinogenicity. Professor Gottfried Lemperle (St Markus Hospital, Frankfurt, Germany) developed the concept of using PMMA microspheres for tissue augmentation. The initial product tested, Arteplast, was heterogeneous, containing various PMMA monomers, spheres of various sizes, and even some impurities. It led to several cases of granuloma formation, with swelling and inflammation. Artecoll (formerly Artefill), which has been available in Europe for a decade, contains only smooth microspheres of 30–40 µm in size and 99% of the remaining monomers have been removed during processing. These changes in the product size and uniformity of particle composition have resulted in a significantly decreased incidence of granuloma formation.

In 1971, Robert and William Gore developed expanded polytetrafluoroethylene (e-PTFE) as an expanded fibrillated form of Teflon (PTFE). It was approved for use in facial and reconstructive surgery in 1993. SoftForm and its softer, more pliable second-generation counterpart, UltraSoft (Tissue Technologies Inc, San Francisco, CA) are sheets, strips, and tubes of e-PTFE used as facial implants to treat depressed scars, lip atrophy, and deep furrows such as nasolabial folds and marionette lines. Given the proliferation of safer fillers, these products have generally become less useful and are no longer available.

AlloDerm (LifeCell Corporation, Palo Alto, CA) is acellular human cadaveric dermis which has been freeze dried. AlloDerm is processed as sheets and has been widely used in the treatment of full-thickness burns, blistering conditions such as epidermolysis bullosa, and in reconstructive surgery for patients with urinary incontinence. It is also used as an implant in soft-tissue augmentation procedures such as rhinoplasty, lip augmentation, glabellar contouring, and scar revision. Cymetra (LifeCell Corporation, Palo Alto, CA) is the injectable form of AlloDerm. Both Cymetra and AlloDerm have been available since the mid-1990s.

Most recently, two novel filling substances, calcium hydroxylapatite (Radiesse) and poly-L-lactic acid (Sculptra), which are considered stimulatory fillers, have been introduced into the filler market. These two fillers are considered “stimulatory fillers” as they induce a fibroblastic response that results in the formation of new collagen and connective tissue. This allows the clinical effects to last for a prolonged duration, which has been reported to range from 12 to 36 months. Calcium hydroxylapatite (Radiesse) (Merz Aesthetics Inc, San Mateo, CA) is composed of calcium hydroxylapatite microspheres suspended in polysaccharide gel. It has been utilized as a soft-tissue filler for augmentation of the nasolabial folds, zygomatic region, under-eye region, and as a non-surgical rhinoplasty treatment to improve nasal contouring. PLLA was initially approved by the FDA in 2004 for the correction of facial lipoatrophy in patients with HIV infection; PLLA was subsequently approved in 2009 as a soft-tissue filler. It has been utilized for the correction of fine lines, wrinkles, folds, and creases as well as for augmentation, repositioning, and contouring of the cheeks and chin. The PLLA microparticles are absorbed slowly over a period of several weeks after injection, but the newly generated collagen and clinical effects have been reported to last for at least 18–24 months. A recent review of filler materials highlighted the usefulness of calcium hydroxylapatite and PLLA in addition to hyaluronic acid.

Although an abundance of injectable soft-tissue fillers exist worldwide, those deemed by the authors to be of most immediate importance to the reader are discussed below and presented in Table 24.1 .

Indications

Fillers either replete defects or augment existing facial structures. Beginning with the upper third of the face, fillers can be used to fill in depressions in the forehead caused by acne scars. Temporal depression that is associated with age may also be augmented, and lines of expression such as glabellar frown lines can be diminished. Filling the upper-third of the face is potentially more challenging because of the concurrence of dynamic creases in this region. In the periorbital region, fillers may be used for “etched-in” crow's feet, with some practitioners advocating using fillers under the lateral eyebrow as a substitute for surgical brow-lift. In the lower eyelid, restoring this subunit's volume rather than removing fat has become a guiding principle in restoration of the upper face. The appropriate use of a filler can remove the “double bubble” between the lower eyelid and the upper cheek as well as camouflage the nasojugal groove.

In the mid-face, fillers can be used to correct traumatic or acne scars. The types of acne scars most amenable to treatment are either atrophic or rolling scars. Sinking and effacement of the malar eminence and hollowing of the cheeks can also be corrected with fillers. While the malar region can be augmented directly, often merely adding volume diffusely to the cheeks will increase the malar prominence. Cheek hollowing is commonly treated with fillers in patients with HIV lipoatrophy. While the thinness of nasal skin may lead to a higher rate of complications or unsatisfactory results with the use of fillers, experienced practitioners can effectively fill scars and alter the profile of the nasal dorsum.

The most popular anatomic areas for injectable soft-tissue augmentation, and the ones with the most prolonged results, are the nasolabial folds and the marionette lines, also known as “smile” lines. Deepening of the nasolabial folds, which are in the transition zone between the mid-face and lower face, creates an abnormal demarcation between these two major facial regions. The desire of even young patients to fill these lines reflects the aesthetic aspiration for a smooth facial contour. A secondary effect of filling these lines is to increase the prominence of the medial cheeks in profile view.

The lower face is dominated by the lips. Fine vertical rhytides of the upper lip can be diminished with judicious use of fillers. Age-related effacement of both the upper and the lower lip margins, as well as thinning of the lips, can also be corrected. Hyaluronic acid fillers can be used in the lips to achieve a natural fullness and can be used to redefine the effaced vermilion border. Marionette or “drool” lines are a combination of expression, aging, and genetics. While a variety of fillers can be used to reduce them, in older individuals or those with advanced actinic damage and sagging, filling them may create ripples lateral to the injection area.

A sign of aging in the lower face is unevenness of the jawline. This is caused not only by loss of skin elasticity and gravity but also because of resorption of the mandible. Selective injection of the appropriate filler can create a smooth and robust mandibular line. Although permanent implants are commonly used for increasing chin projection, fillers can temporarily create an attractive prominence at this point. Use of fillers for this indication may allow the patient to determine if he or she desires a permanent implant.

Preoperative Preparation

Minimal preoperative preparation is required for soft-tissue augmentation. With the diversity of products available, the physician should advise the patient of the strengths and potential pitfalls of various products. Patient and physician should come to a mutual agreement regarding which product would best suit the patient's needs, downtime, and risk tolerance. Physicians should set realistic patient expectations for adverse reactions, post injection side effects, and duration of correction, prior to deciding on the substance to be utilized for soft-tissue augmentation ( Box 24.1 ).

The cosmetic consultation should prioritize the patient's concerns and devise an overall treatment plan. During this discussion, a distinction should be made between lines of expression, static wrinkles, and sagging, and the appropriate therapies for each should be explained. When it is determined that fillers are the best therapy for a given cosmetic concern, several alternative approaches and materials should be considered. It should be explained to the patient why the practitioner believes that that particular filler and injection technique is the best choice. Reviewing common postoperative sequelae such as bruising is important; rare but serious potential adverse effects should also be discussed, if appropriate. If the filler is being used off-label, this fact should be disclosed to the patient.

A complete medical history, including medication list, should be elicited. When medically appropriate, patients should discontinue non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, high-dose vitamin E, and most herbal medications prior to injection to decrease risk of ecchymosis. This is particularly important prior to injection of the thin skin of the eyelids and lips. As with any invasive procedure, the patient may be asked not to take aspirin for at least 8 days, or NSAIDs for at least 5 days, unless discontinuation of these poses a significant risk to the patient. If the patient is on warfarin therapy, the prothrombin time (PT) may be checked; generally if the PT is under 2.0, then the risk of hematoma or excessive bruising from injection is low. Herbal medications (e.g., ginkgo biloba, St John's wort, vitamin E, garlic, ginseng, fish oil) that predispose to bleeding should be held, if possible.

Preoperative ingestion of some homeopathic medications (e.g., arnica) may reduce bruising, although further investigations are needed to substantiate this effect. Some physicians find that preoperative photos from the frontal, oblique, and profile angles are useful for documenting the results of an injection procedure. There are very few absolute contraindications to prepackaged injectable fillers. A patient with a known allergy to a specific filler would not be a candidate for the procedure.

Technical Aspects and Overview of Commonly Used Products

The most commonly used FDA-approved injectable filler materials currently available in the USA are listed in Table 24.2 . ( Video 24.1 .)