Soft-tissue fillers

4 Soft-tissue fillers



Trevor M. Born, Lisa E. Airan, Dimitrios Motakis




Synopsis




image The availability of multiple safe soft-tissue fillers today offers a unique tool in the correction of facial wrinkles and in the restoration of the volumetric loss that appears with aging.


image Reversibility is more often than not an advantageous property of fillers, allowing adjustments that may be needed due to technical errors or changes in the tissues that may occur with aging.


image Inexperienced injectors should always opt for rapidly resorbable fillers such as hyaluronic acid (HA). This allows for faster resolution of any technical errors that may occur. Hyaluronidase can be used to dissolve the filler.


image With respect to the treatment of deep folds and tear troughs, it is important to undercorrect these deformities. This results in a more natural appearance, and leaves room for further correction in the future if that is desirable. Overcorrection of these areas can result in visible abnormalities.


image “Off-label” use of synthetic materials is technically possible but does carry some risk. The plastic surgeon is vulnerable from a liability standpoint, and should use discretion when using products in an “off -label” manner. The patient must be informed of “off-label” use.


image In cases where slight correction is required, patients often forget their preoperative appearance. It is imperative to use photography and point any asymmetries prior to injection.


image Complications of dermal fillers can be avoided by the use of proper technique (small aliquots, appropriate level and quantity of injection, undercorrection, massaging with some fillers).



Introduction


There has been historical interest in the use of injected material to modify the contour of skin and underlying soft tissue. However, effective and safe tools to accomplish such a goal have become available only in recent decades. The plastic surgeon now has access to numerous fillers to soften the stigmata of aging or correct the contour deficits that occur with many disease processes. In order to use the soft tissue optimally, one has to understand the nature of each product and its mode of integration and adsorption.


The goal of this chapter is to present the different classes of fillers and the indications and techniques for their use. Particular attention is paid to the correction of common areas in the face. Furthermore, we will present possible contraindications and complications of fillers and how to avoid or treat them. Prior to mastering the use of soft-tissue fillers, it is important to understand how wrinkles form.



The pathophysiology of wrinkles


Aging is a complex process, which is the result of both intrinsic factors (soft-tissue maturation, skeletal change/atrophy, and muscular hyperactivity) and extrinsic factors (gravity and solar damage). As a consequence, the smooth confluent appearance of the face is slowly replaced by sharp angles, fine and deep wrinkles, and abrupt hollows and bulges. The anatomy of facial aging is thoroughly reviewed in Chapters 6 and 11.


With aging, skeletal changes occur with an overall decrease in facial height and a moderate widening and deepening of the facial structure. The decrease in maxillary height and the increase in orbital volume result in sunken eyes, and less space for attachment of the available soft tissue. The cheeks descend, the nasolabial folds become deeper, the upper lip complex appears bulkier and tear troughs as well as perioral rhytides appear. If teeth are lost, alveolar height decreases and the chin atrophies. Apart from the decrease in overall bone volume, the ligamentous attachments of the soft tissue and skin become lax and further contribute to the appearance of furrows and creases.


With chronological aging, all cells divide more slowly; this includes keratinocytes, fibroblasts, and melanocytes. The epidermis thins out and the epidermal–dermal junction becomes flatter, while the integrity of the stratum corneum decreases and the basal cells acquire more atypia. As a result of this decreased integrity, water loss through the skin is increased, leading to skin which is drier, more fragile, and more prone to shearing. The dermis becomes thinner and contains fewer but thickened elastic fibers and fewer loosely woven collagen fibers. Sebaceous glands become hypertrophic, but are less numerous and less active, thus contributing to skin dryness. All the above changes lead to a drier, less elastic, coarser, more fragile skin that is susceptible to gravitation forces and thus wrinkling.


Chronic sun exposure is probably the most significant environmental factor impacting skin maturation, leading to dyschromia, lentigines, telangectasias, and the loss of the youthful pink hue. Skin texture becomes coarser. The epidermis is actually thicker in photoaged skin than in normal skin. Overall collagen amount decreases. However, in the superficial dermis there is an area of increased normal collagen production (grenz zone) representing a chronic inflammatory process known as heliodermatitis. Solar elastosis is pathognomonic of photoaged skin with abundant, degraded, thickened elastic fibers. Lastly, sun exposure contributes to a reduction in ground substance, contributing to deeper folds and wrinkles.


Microscopically all wrinkles appear like thinned breaks in the dermis. Even though the terms wrinkles, folds, creases, furrows, and rhytides are often used interchangeably, specific features can be used to distinguish between different types of rhytides. Fine wrinkles refer to changes in the texture of the skin that involve the superficial aspect of the dermis. Mimetic wrinkles can extend down to the middle level of the dermis (lines) or down to its full thickness (furrows). These are due to the repeated folding of the skin secondary to the contraction of the facial muscles. As a result they are perpendicular to the direction of these muscles and occur in locations such as the glabella, periorbita, forehead, and lips. These dynamic wrinkles eventually become static, remaining visible even when the underlying muscle is relaxed.


Folds refer to larger grooves with some level of skin overlap. These are the result of soft-tissue descent secondary to gravity, decreased support, and loss of skin elasticity. Examples include upper eyelid dermatochalasis, nasolabial folds, jowls/marionette lines, and horizontal neck lines. The tear trough is an infraorbital groove that results from soft-tissue tethering along the arcus marginalis between bulging orbital fat above and descending soft tissue below.


The importance of being able to classify wrinkles is central to being able to direct treatment.1 Superficial lines that course at the upper level of the dermis are amenable to dermabrasion, chemical peels, and lasers. On the other hand, mimetic wrinkles respond to muscle inactivation with Botox or myectomy/myotomy. Mimetic wrinkles can also be improved with the concomitant use of dermal fillers. Dermal fillers are also useful in the treatment of folds during their early stages, or as an adjuvant modality to surgery, during their more advanced stages. Several classification systems have appeared over the years. The Lemperle classification is based on wrinkle depth and is helpful in guiding treatment and assessing change/improvement (Table 4.1).


Table 4.1 Biological fillers approved by the Food and Drug Administration (FDA) in the United States




































FDA-approved biological filler Type
Cymetra Human dermis
AlloDerm Human dermal matrix
Dermalogen Human collagen matrix
Surgisis Porcine collagen matrix
Fascian Human tensor fasciae latae
Zyderm/Zyplast Collagen (bovine)
CosmoDerm/CosmoPlast Collagen (human-based)
Restylane/Perlane Hyaluronic acid (bacterial)
Elevess Hyaluronic acid (bacterial)
Juvederm Hyaluronic acid (bacterial)


Historical perspective


The earliest reports of tissue augmentation by subcutaneous implantation of small adipose grafts appeared over a century ago with German surgeon Neuber.2 Later, with the discovery of the syringe, Brunning first injected fat in 1911. However, significant resorption and fat necrosis put this technique on the backburner. It was not until liposuction and the concept of microfat grafting that the use of lipoaspirate for soft-tissue augmentation successfully resurfaced.


Concurrent with the initial efforts to graft fat came attempts to inject other synthetic materials in order to volumize soft tissue.2,3 In 1899 Robert Gersuny first injected Vaseline, while later, Eckstein used paraffin to correct fistulas and hernias and to attain aesthetic soft-tissue augmentation. Serious complications such as granulomatous inflammatory reactions (paraffinomas) and nodule formation, embolization, and migration were reported early on, yet paraffin kept being used for over two decades before it was abandoned.


The first reports of the use of silicone date from the end of World War II in Japan when numerous women had their breasts injected with nonmedical-grade silicone.4 Shortly after, in 1947, Dr. James Barrett Brown first used silicone for the correction of soft-tissue deficits in the US. Concurrently, hard and rubber silicone found use in creating alloplastic implants. Early flawed animal experiments as well as toxicological studies deemed the use of injectable silicone safe and physicians relied heavily on this improper information. The popularity of the technique led to numerous complications such as lump formation, firmness, ulceration, extrusion, and migration. The illicit use of silicone continued in the US well into the 1990s when the US Food and Drug Administration (FDA) took a more active role in criminalizing its use. In 1992, because of the lack of adequate data to prove its safety, the injection of silicone for either research or clinical reasons was officially abandoned for a while in North America. At the time of writing, highly purified silicone (AdatoSil 5000, Silikone 1000) is approved for the treatment of retinal detachment. Even though these products can be used “off-label” for soft-tissue augmentation, the safety data to back up such practices are not available.5,6


In 1981, bovine collagen was the first filler approved by the FDA for soft-tissue augmentation; it soon became the gold standard against which all fillers were compared. Its rapid resorption and allerginogenic nature led to a series of efforts to develop a compound that would not cause allergic reactions and that would last longer. It was not until two decades later that HA became available for clinical use. HA found multiple medical uses before it was approved in the US as a soft-tissue filler. HA dermal fillers have replaced collagen as the gold standard in cosmetic soft-tissue augmentation.


The high demand and success of HA products led to an intense search for products that were similar to HA, did not cause hypersensitivity reactions, but lasted longer.7 This in turn led to a number of newer and longer-lasting products such as poly-l-lactic acid (PLLA: Sculptra, FDA approval in 2004), calcium hydroxyl apatite (Radiesse, FDA approval in 2006) and polymethylmethacrylate (PMMA)/polyacrylamide products such as ArteFill (FDA approval in 2006). Today, plastic surgeons have in their armamentarium numerous safe fillers that can produce unprecedented aesthetic results, provided that they are used in an educated manner.



Classification of fillers


Soft-tissue fillers are an ideal option for patients seeking facial rejuvenation with minimal downtime. For the young patient not requiring surgery, these materials offer a viable option, while for older patients, surgery can be combined with fillers and other surface treatments to create an optimal result.8,9


The number and variety of products available are impressive.10–12 Yet the ideal filler has not been found; neither have we agreed on the properties that would be appropriate for all fillers. For example, although permanence would clearly be a virtue, it could also be a negative if the filler used did not age appropriately as the patient’s soft tissues became ptotic and attenuated.13,14 Therefore reversibility is an important characteristic. Despite these reservations, there are certain basic qualities that are sought in the ideal filler material (Box 4.1).



Box 4.1


Ideal filler characteristics




• Nontoxic


• Biocompatible


• Long-lasting (if not permanent)


• Reversible


• Off the shelf


• Autologous


• Easy to use


• Safe


• Produces positive, natural, discernible change


• Minimal downtime


• Level of placement (could be placed through dermis at subcutaneous, intramuscular, or periosteal levels)


• Predictable (permanence, bulk, and behavior)


• Performs well as a person ages


• Not discernible by touch/appearance


Worldwide research for the ideal soft-tissue filler continues, although a balance is needed between embracing new products and ensuring the patient safety. In order to understand better the properties of each product that is either already available or in the pipeline, fillers can be classified under the following categories:



• autologous materials


• biologic materials


• synthetic materials.



Autologous fillers


Autologous materials are derived from the patient’s own tissue.15–18 They come closest to matching the description of the ideal soft-tissue filler in terms of safety, but they are not as convenient to use. They have to be harvested from another site on the body, which may produce a scar, and the process of harvesting and then inserting these materials elsewhere requires a two-step procedure. Toxicity, allergenicity, immunogenicity, carcinogenicity, and teratogenicity are not issues, but there can be problems with infection, migration, inflammatory reactions, loss of persistence, and reproducibility. Autologous fillers include:



• dermis, fascia, cartilage, superficial musculoaponeurotic system (SMAS), breast implant capsule


• fat grafts


• platelet-rich fibrin matrix (PRFM)


• cultured fibroblasts.


Dermal, fascial, and cartilage grafts have a long history of use in plastic surgery, and with careful handling and placement in an appropriate recipient bed these grafts may have very good, long-lasting results. Less volume survives when lipodermal grafts are used because it is the dermal surface that must derive the blood supply from the host and serve as a vascularizing carrier for the fatty elements. Similarly, fascial grafts from the fascia lata of the thigh, the temporalis, and the SMAS can be used. In a good recipient bed, fascia is permanent and persists through a combination of creeping replacement by host fibroblasts and continued viability of fascial fibroblasts.


Fat grafts as free en bloc transfers of tissue have the disadvantage of losing at least one-half of their bulk after transplantation, and they develop cysts, calcifications, and necrotic lumps. However, this is not the case with injectable fat grafting: small intact packets of fatty tissue are harvested as atraumatically as possible and injected in tiny amounts along multiple tracts. The purpose is to keep the injected fat cells near a blood supply for survival and integration. The great advantage of injectable fat grafting is that it is permanent if the fat survives. The disadvantage is the unpredictability of the survival, the need for a donor site, and the time required to process and inject the tissue.15–17,19


Selphyl (Aesthetic Factors, Princeton, NJ) is a patented system that allows the extraction of PRFM from the patient’s own blood.20,21 This novel technology allows processing of blood in the office in a three-step process that takes approximately 20 minutes. The collected PRFM is then injected into the patient’s wrinkles. The collection of a 9-cc blood sample allows the collection of 4 cc of PRFM. The development of collagen and dermal matrix increases over a period of 3 weeks and there is early evidence to suggest long-lasting wrinkle correction (up to 20 months). Possible applications include correction of nasolabial folds, glabellar lines, and panfacial rejuvenation, as well as acne and other scar treatments. Selphyl has been cleared for use in the US (FDA) and Europe (CE mark). Although additional long-term data are still required to prove its efficacy, this product represents the first practical modality for autologous wrinkle collection.


More recently, LAVIV or Azficel-T (Fibrocell Science, Exton, PA: www.fibrocellscience.com; FDA approval June 2011) became approved for the correction of moderate to deep nasolabial folds. LAVIV is an autologous cellular product composed of fibroblasts harvested from postauricular skin (www.mylaviv.com/pdf/LAVIV-prescribing-info.pdf). The fibroblasts obtained from the skin biopsy are aseptically cultured and expanded until sufficient cells for three consecutive injections are obtained. The treatment sessions are spaced 3–6 weeks apart. Although the mechanism of action of LAVIV is unclear, a two-point improvement in the Lemperle classification scale was achieved in up to 57% of subjects treated. The longevity of this correction beyond 6 months remains to be shown.



Biologic fillers


Biologic materials derived from organic sources (humans, animals, or bacteria) offer the benefits of ready “off-the-shelf” availability and ease of use, but introduce issues of sensitization to foreign animal or human proteins, transmission of disease, and immunogenicity.22–26 Biologics provide only a temporary effect and typically do not correct the wrinkles or creases completely. The three major types of biologic tissue fillers are acellular soft-tissue matrix, collagen, and HA products (Table 4.1).


Fascian (Fascia Biosystems, Beverly Hills, CA) is a preserved particulate human fascial graft that is marketed in syringes and is prepared from prescreened human cadaver fascia lata. It is injected intradermally, subdermally, or in deep tissue, depending on the application and it is reported that Fascian particles tend to last two or three times longer than bovine collagen products.


AlloDerm (LifeCell, Branchburg, NJ) is an acellular, structurally intact sheet of human dermal graft that was first used clinically in the treatment of full-thickness burns. Processed from prescreened human cadaver skin, the cells responsible for immunogenicity are removed while the matrix structure and biochemical components are left intact. The grafted material then acts as a template for recipient cell repopulation resulting in soft-tissue regeneration. Some of its cosmetic-related applications include lip augmentation, nasolabial fold correction, glabellar wrinkle softening, rhinoplasty (dorsum and tip) as well as septal perforation, Frey syndrome, liposuction defect, and scar treatments. Complications include infection, persistent palpability or lumpiness, and variable “take” of the grafted material. Reports of volume diminution in mobile graft areas range from 30% to 40% at 1 year to 70% retention after 18 months.


Cymetra (LifeCell, Branchburg, NJ) is also a lyophilized acellular collagen matrix derived from human cadaver dermis, but in a particulate form. It is FDA-approved for subcutaneous injection and is used for lips, nasolabial folds, and deep wrinkles. Dermalogen, an injectable human cadaver-derived collagen matrix, is no longer available.


Surgisis (Cook, Bloomington, IN) is a lyophilized collagen matrix that is derived from a porcine source and marketed in sheets of various sizes and thicknesses. Even though it is used as a fascial replacement, there is less information about its use for aesthetic applications at this time.


Bovine collagen, marketed as Zyderm and Zyplast (Allergan, Irvine, CA), became available in 1981 and is a unique product. It was the first commercially marketed injectable approved by the FDA for soft-tissue augmentation; it has been used in millions of patients and it has been the standard against which all other injectables were compared before HA fillers appeared. CosmoDerm and CosmoPlast (Allergan, Irvine, CA) contain human collagen and do not require a pretreatment skin test. Isolated and purified from human dermal tissue and grown under controlled laboratory conditions, the fibroblasts are screened for pathogens and the collagen is subjected to viral inactivation.27–29


HA is a glycosaminoglycan common to most living organisms and is a component of connective tissue of the skin, cartilage, bone, and synovial fluid. In human skin, HA adds bulk and acts as a shock absorber and lubricant. HA binds water and after injection maintains a bulking effect as it is degraded, a process that has been called “isovolemic degradation.” Restylane (Q-Med, Uppsala, Sweden) is a HA soft-tissue filler that received FDA approval in December 2003 for use in the correction of facial wrinkles.7,30–39 It is marketed as three products differing in the size of the constituent particles: Restylane Touch (Fine Lines), Restylane, and Perlane. The Restylane products are manufactured by recombinant technology in bacteria, thus eliminating skin testing. The shelf-life of Restylane is 1.5 years while longevity is 6–12 months depending on the location treated and the injection technique. Elevess (Arnica Theurapeutics, Bedford, MA; FDA approval 2006) is a newer product that contains higher concentrations of HA as well as lidocaine and is intended for medium wrinkles and deeper folds. Prevelle Silk, produced by Mentor, was introduced in the US in 2008 and it is equivalent to Restylane. In 2006, Allergan’s Juvederm series of HA fillers received FDA clearance. Juvederm fillers come in various concentrations and viscocities. Even though in Europe they are labeled as Juvederm Ultra 2, 3, and 4 and Juvederm Voluma, in North America they are marketed as Juvederm Ultra and Juvederm Ultra Plus and may contain lidocaine (Juvederm XC). Alternatevely, lidocaine (usually 2%) can be mixed with most fillers to achieve numbing during injection. There are a large number of non-FDA-approved biological fillers, which are available in the rest of the world.40 These are mainly HA-based products with various sources, processing and cross-linking (Table 4.2).


Table 4.2 Biological fillers not approved by the Food and Drug Administration (FDA) in the United States































































Non-FDA-approved biological fillers Type Country (approval)
R-fine Hyaluronic acid Canada, Europe, Asia
Hyaluderm Hyaluronic acid Europe
Revanesse/ReDexis Hyaluronic acid (cross-linked) Canada
MacDermol S/MacDermol R Hyaluronic acid (avian, cross-linked) Europe
Varioderm NASHA Europe
Amalian NASHA Europe
Macrolane NASHA Europe
Teosyal NASHA Europe, Canada
Zetaderm/ Zetavisc NASHA Europe, Canada, Russia
HydraFill NASHA (cross-linked) Europe
Esthelis/Fortelis/Belotero NASHA (CMP technology cross-linked) Europe, Canada, Asia
Puragen NASHA (DXL technology cross-linked) Europe
Rolifan/Philoderm/Beautygel/ Esthirase/Coilingel NASHA (cross-linked) Europe, Canada, Brazil
HyalSkin NASHA (BDDE cross-linked) Europe

NASHA, nonanimal-stabilized hyaluronic acid.



Synthetic fillers


Synthetic materials can offer permanence. Many injectable and surgically implantable synthetic products have been used over the years, and many have been condemned for complications, including granulomas, acute and delayed infections, migration or displacement, and deformities that can result from complications or removal of the material. It is with these products that the difference between the regulatory process in the US and that in the rest of the world is highlighted. The FDA controls access to the US market and enforces strict “labeling” practices, which means that the manufacturer must spell out the exact applications for which the material has been approved. Synthetic fillers approved by the FDA appear in Table 4.3.


Table 4.3 Synthetic fillers approved by the Food and Drug Administration in the United States





















FDA-approved synthetic fillers Type
AdatoSil 5000 Silicone
Silikon 1000 Silicone
ArteFill (Artecoll) Polymethylmethacrylate (PMMA)
Radiesse Calcium hydroxyapatite
Sculptra (New-Fill) Poly-l-lactic acid (PLLA)

AdatoSil 5000 and Silikone 1000 are silicone gels with improved viscosity that have been approved by the FDA for use in treating detached retina. They are not approved for cosmetic use in the US, and caution is advised with these products. Historically, injectable silicone products have tended to harden, migrate, and cause inflammation and skin necrosis.4,41 Bioplastique is composed of solid silicone microparticles (100–400 µm), which have been vulcanized, texturized, and placed in a polyvinyl pyrrolidone carrier. Injected dermally, the carrier is resorbed, and the silicone microparticles are encapsulated in host collagen, which prevents migration and effects permanent correction. It is used in many parts of the world but is not approved by the FDA for use in the US because of concerns about granulomatous reactions and permanent lumps that can only be removed with surgery.


ArteFill is a permanent injectable implant consisting of polished PMMA microspheres suspended in bovine collagen in a 20–80% ratio.42–44 After injection, the collagen is resorbed and the round, smooth microspheres are encapsulated by host collagen where they are stabilized and become permanent. Used in Europe for the past decade as Artecoll, ArteFill was approved by the FDA in October of 2006.


image Video 1


Radiesse is a mixture of calcium hydroxyapatite (30%) and polysaccharide gel (70%).44–50 The polysaccharide gel is very white, which makes Radiesse inappropriate for use in the dermis. Radiesse is FDA-approved (since December 2006) for nasolabial and labiomental crease correction. Potential concerns about its use as a soft-tissue filler include clumping, lumping, granulomas, and migration of the microspheres. It is reported to last anywhere between 1 and 2 years.


Sculptra is composed of PLLA (poly-l-lactic acid).29,51–53 Because it is not made from human or animal sources, it does not require a skin test. PLLA is a biocompatible, biodegradable material that has been used in surgical products for more than 20 years as a component of dissolvable sutures. Sculptra has been safely used outside the US since 1999 in over 30 countries under the trade name of New-Fill for a variety of facial volume and contour deformities. It was approved by the FDA in August of 2004 as the only product for the correction of human immunodeficiency virus (HIV)-associated facial lipoatrophy and is now approved for cosmetic use in the US. It is injected subcutaneously in the area of fat loss/volume loss and provides a gradual and significant increase in volume. It is reported to last up to 2 years after three consecutive treatment sessions, approximately 1 month apart.


A large number of other synthetic fillers are available in various parts of the world and a few are listed in this chapter40,

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Feb 21, 2016 | Posted by in General Surgery | Comments Off on Soft-tissue fillers

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