Facial soft-tissue augmentation has become increasingly popular as an option for those patients in whom age-related changes manifest as contour defects or who desire volume enhancement for various areas of the face. A variety of agents and techniques are currently available that, when used appropriately, can improve or correct facial rhytids and regional volume depletion. Failures of some agents are due to reduced biocompatibility, inadequate administration technique, or failure to match the actual underlying defeat with the most appropriate solution. Dermal soft-tissue augmentation with human tissue collagen matrix (Autologen and Dermalogen) is physiologic, appears to be ultimately safe and effective, and has many qualities consistent with an ideal dermal filler. Several autologous, allogeneic (cadaver-derived), heterologous, and alloplastic agents will be discussed in this article with regard to rationale, patient selection, optimum administration technique, and persistence.
Coincident with the malpositional changes of the face that occur with age is the soft-tissue volume depletion that manifests as reduced subcutaneous fat and loss of dermal collagen1 (Fig. 1). A variety of filling agents have been tried, with varying success, in attempts to address volume depletion and soft-tissue contour defects.2
The ideal agent for facial soft-tissue augmentation should be safe and effective; easy to obtain and administer; have a minimal risk for infection, extrusion, or migration; produce a minimal inflammatory reaction; and last for an acceptable degree of time. It should also be cost-effective, show consistency and reproducibility, and ultimately yield highly acceptable, positive aesthetic results.
Over the past two decades, aesthetic surgeons have accumulated experience with various injectable agents for soft-tissue augmentation, most notably, bovine collagen and autologous fat. A considerable degree of confusion exists, however, regarding which agent works best in any particular situation and the causes of failure of many of the agents used in the past. To resolve this dilemma requires a greater understanding of the actual changes occurring in any facial region that cause the visible contour defect; a sound treatment rationale, with physiologic solutions to varied, individualized circumstances; and selecting the agent or technique that most effectively remedies each problem.
The most physiologic solutions tend to give the most natural and longest lasting results. For example, deep contour defects, such as those seen in hemifacial atrophy, overresection of regional facial fat after an aesthetic procedure, or age-related changes with deeper plane volume depletion, are best addressed by the replacement of the depleted soft tissue, namely, subcutaneous fat. This can usually be done by lipotransfer, as has been discussed previously.3 Fat injections are most often administered at the time of fat harvesting. Results have been highly variable and are strongly technique-dependent. More superficial contour defects that are primarily adynamic or static, such as facial rhytids, scars, or other dermal depressions, are most effectively and physiologically treated with "like material," such as dermal collagen (dynamic facial rhytids are often most appropriately treated with chemodenervation4). Bovine collagen has, until recently, been the collagen type most readily available.5
The concept of heterologous trans-species dermis replacement and augmentation originated in an attempt to have an economical, "off the shelf" product to replace lost human dermal collagen; the human collagen was replaced by a bovine substitute rendered nonimmunogenic.6 The assumption was that by cleaving the telopeptide (end-protein fragments) from the central (helical) portion of the bovine collagen molecule (Fig. 2), the molecule would be nonimmunogenic. It was thought that the primary interspecies variability of the heterologous animal protein resided in this region. However, this process likely further destabilized the collagen structure, causing unraveling of the helix that yielded incomplete (molecular) collagen fragments and possibly enhanced immunogenicity by exposing other, previously concealed aspects of the molecule. The result was a relatively amorphous gel consisting of incomplete bovine collagen molecule fragments. Results from bovine collagen have been disappointing and seem to persist for approximately 3 months. Tachyphylaxis is common, and most recipients experience a diminished longevity of effect with repeated treatments (Fig. 3).
The reported allergy to bovine collagen is anywhere from 3 to 10 percent.7,8 This represents the population that has had skin testing and revealed a positive reaction, thereby eliminating their candidacy for injectable bovine collagen (Zyderm I and II and Zyplast, Collagen Esthetics, Palo Alto, Calif.). There is a considerably smaller but significant subgroup of allergic patients who develop an allergy to bovine collagen after one (and often, two) negative skin tests (Fig. 4). These reactions can be devastating and difficult, if not impossible, to treat (Fig. 5).
Additionally, I believe that the positive aesthetic effects of bovine collagen with regard to the reduction of rhytids and dermal soft-tissue augmentation are due more to the inflammatory edema caused by the injected foreign protein, yielding smoother dermal contours and augmentation, and less from actual soft-tissue augmentation by the injected material (Fig. 6). This may also explain why even novice injectors could obtain reasonable results, because the diffuse inflammatory tissue edema occurred whether a homogeneous layer of collagen was injected or if deposition was irregular. Is this, however, a chronic allergy? What other immune effects are at play here? And finally, is the tachyphylaxis (reduced effect or longevity of the injected agent with subsequent treatments) often seen with bovine collagen due to sensitization? If so, it seems that mechanistically, individuals develop either an acute or a chronic reaction to the foreign protein.
The positive short-term soft-tissue effects with bovine collagen, however, can be highly aesthetic, which has led to the search for other, better tolerated, more physiologic agents that would reduce or eliminate untoward effects and improve persistence. The resurgence of interest in autologous fat, in fact, occurred at about the same time as the growing disenchantment with bovine collagen. However, confusion regarding the interchangeability of the two treatments arose. Simultaneously, an interest evolved in an autologous agent for dermal augmentation and other medical applications that would be tolerated, safe, and effective.9-13
A multitude of alloplastic agents have been tried and abandoned or have become recently popularized; these include microdroplet, injectable liquid silicone,14 expanded polytetrafluoroethylene15 (ePTFE-Soft Form, Collagen Esthetics), and bovine collagen-wrapped polymethylmethacrylate microspheres (Artecol, Rofil Medical International, The Netherlands).16 Silicone had been widely available, and results are, at times, excellent. The emergence of other alloplastic agents seemed to be a response to the reduced availability of injectable silicone and unsatisfactory persistence of other biomaterials; however, they also had risks of infection, extrusion, and migration. Persistence was also a problem with these materials with poor placement and migration.
Other biomaterials have emerged; they also seem to be a response to a variety of concerns with bovine collagen. Injectable hyaluronic acid (Hylan B/Hylaform Gel, Biomatrix Inc., Ridgefield, N.J.),17 a native but nonstructural component of the dermis, has recently emerged. This agent delivers transient soft-tissue augmentation at best, with a lack of any long-term persistence. Isolagen18 (Isolagen Technologies, Paramus, N.J.) also spawned interest; it was an attempt to stimulate in vivo neocollagen formation through an injection of what is presumed to be an ultradilute suspension of autologous fibroblasts into the target area, with the expectation of delayed-onset tissue augmentation that would occur over the months after injection. Results with this agent, however, have also been generally disappointing.