Modern society has more and more individuals looking to aestheticians and physicians to help them achieve a more youthful appearance. The skin’s natural aging process manifests itself as contour changes, wrinkles, the depletion of subcutaneous fat and the loss of dermal collagen, and traditionally, rejuvenation of these changes has been achieved with a face-lift by surgically tightening the skin. Nowadays, a multitude of minimally invasive procedures are aimed at rejuvenation without the risk, recovery time, and expense of major surgery, and it is the development and popularity of BOTOX® that has opened the door for equally non-invasive, adjunctive treatment of more superficial contour irregularities and wrinkles. In this article, we will attempt to provide a brief filler history and overview of what is commonly used.
Dermal filling is not a new treatment. As early as the 1890s, doctors had the technology to take fat from patients’ arms and inject it into their faces. In fact, fat is still a popular substance used by some practitioners today who can move fatty tissue from an area of the body where it is not required and inject it somewhere else.
In the mid 1900s, doctors were using paraffin as filler in the skin until a high incidence of foreign body granuloma formation was discovered. The resulting concerns regarding safety further prevented it from being used widely. In the 1940s, the use of highly refined injectable silicone emerged as a dermal implant, with excellent cosmetic results and high use potential. However, because of the high abuse potential and problematic adverse effects from contaminated composites, its use as a cosmetic agent has been subsequently banned. The last twenty-five years have seen an explosion in technologic advances contributing to a cascade of new dermal implant materials. Injectable bovine collagen was developed in the 1970s, and approved by the FDA in 1981. It remained the industry criterion standard for many years until the development of human derived collagen fillers.
In the 1980s, new techniques using reconstituted human serum product that worked by forming clots, which, in turn, stimulated collagen synthesis were developed. However, in the face of the AIDS epidemic and a concern for blood-borne diseases, they were consequently taken off the market. The same process survives in a slightly different form today, where the patients own skin provides the basis for the implant material.
With the emergence of liposuction in the late 1970s, fat once again became a convenient source for tissue augmentation, and in the late 1980s, autologous collagen processed from harvested fat was first used for dermal augmentation. The most recent advances in dermal filling technology are in the form of hyaluronic acid derivatives, harvested and cultured autologous dermal implants, allogeneic products, and synthetically derived products. Continuing research that promises further advances, such as recombinant human collagen are on the horizon. The use of modern, non animal based fillers grows in popularity
The popularity of dermal fillers worldwide is on an exponential growth curve that is led by the United States. There, statistics sourced from the American Society for Aesthetic Plastic Surgery (ASAPS) show that collagen injections were the sixth commonest aesthetic procedure in the U.S. with more than 785,000 treatments in 2004 alone, This represents a 26% increase compared to 2003 figures (620,000 treatments).
New age, hyaluronic acid based fillers were beating collagen injections to fifth place in the commonest aesthetic procedure in the U.S. with over 880,000 treatments in 2004.
As the use of dermal filler products has grown, so has the choice of different filler substances. There are many types from traditional bovine through to synthetic compounds, with various opinions and claims of effectiveness. Manufacturers of modern dermal fillers have been claiming that their products last longer than older fillers, and even that their effects can be permanent. Here is an overview of the most common types used over the past 25 years. Bovine collagen
Bovine collagen was the first legally approved product for soft tissue augmentation in the United States in the early 1980’s, and was considered the standard against which all other dermal implants were measured before the introduction of human collagen derived products.
Results can last 3-18 months, although many recipients report that repeat treatment is usually required at 3-5 months. The sterile, purified, fibrillar collagen used is derived from the hides of isolated herds of domestic cattle, thereby negating the possibility of contamination with the bovine spongiform encephalopathy virus or prion that causes mad cow disease.
Typical bovine collagen fillers consist of 95-98% type I collagen, and the remainder is type III collagen. Overall bovine dermal collagen by weight varies between 3.5-6.5%.
It is reported that as many as 5% of patients may experience hypersensitivity to injectable bovine collagen. Other variations include mixtures of solubilized elastin peptides with bovine collagen.
Bovine collagen is characterised by its braided fibre bundles
Human derived collagen
There are a number of fillers consisting of natural human collagen grown under controlled laboratory conditions.
Until the development of these human derived fillers, bovine collagen was the industry leader. Two common products are Cosmoderm and Cosmoplast.
Both products contain 35 mg/mL of human-derived collagen in phosphate-buffered physiological saline containing 0.3% lidocaine. Cosmoderm is not cross-linked and is used to treat superficial lines and wrinkles, whereas Cosmoplast is cross-linked with glutaraldehyde and can be used for deeper wrinkles.
There is reportedly virtually no risk of causing a hypersensitivity reaction with these human derived fillers.
Autologous collagen
Autologous collagen is a little different that traditional “injected” fillers, and works by promoting an inflammatory response that, in turn, results in the deposition of new collagen at the recipient site. Harvested autologous fat from surgical procedures such as liposuction, is processed by mixing it with sterile distilled water and then by allowing it to freeze, thereby leading to the rupture of adipocytes.
The liquefied fraction of intracellular triglycerides is then suitable for intradermal injection. This technique is often used in conjunction with subcutaneous fat transplantation. The benefit of this technique is its autologous nature, negating the need for hypersensitivity testing. However, it requires harvesting the tissue from a donor site as well as involved preparation and expedient administration after harvesting the tissue. Studies vary on the duration of autologous collagen; the range is months to years, depending on the methods used in fat harvesting, processing, and transplanting.
Use your own!
The ultimate in compatibility must be the Autologen method. This filler is a sterile suspension of collagen fibres prepared from the patient’s own tissue. Three square inches of harvested skin are sent to the manufacturer and yield 1 ml of approximately 3.5% collagen. It is then injected into the superficial mid dermis to treat fine lines, wrinkles, scars, and lip atrophy.
The benefits of this method are that it does not require skin testing and that it lasts longer than bovine collagen. The main drawbacks are that it involves dermal harvesting from a donor site and that it requires careful timing of the procedure since it must be used within several hours of delivery. The favourable results report as much as 75% persistence at 12 months. Different viscosity fluids may require local aesthesia
Recycled skin?
There are products that are spin-offs from burns rehabilitation that have found their way in to aesthetic medicine. Cymetra is a micronized, injectable filler used in soft tissue augmentation procedures such as rhinoplasty, lip augmentation, and scar revision. It is injected into the dermis just over the dermal-subcutaneous junction. Cymetra is derived from AlloDerm, a cellular human cadaveric dermis that has been freeze-dried. AlloDerm is processed as sheets and was widely used in the treatment of full-thickness burns and blistering conditions, such as epidermolysis bullosa. It is a thick, viscous material, and a 23- or 26-gauge needle is often required for injection, which necessitates local or regional aesthesia. Reported results typically last 3-6 months.
Hyaluronic acids
Hyaluronic acid is a polysaccharide found in the dermis of all mammals. When injected in gel form, it can perform very well as a dermal filler. One form known as Hylaform gel, is a form of cross-linked hyaluronic acid (5.5 mg/mL) derived from the rooster combs of domestic fowl.
It is reported to be less immunogenic and longer lasting than bovine collagen. One study showed 86% histologic persistence of Hylaform gel compared with 25% of bovine collagen in guinea pigs at 26 weeks. Although Hylaform gel is widely used throughout the world for dermal filling of scars and wrinkles and in lip augmentation, it has only been recently approved in the United States.
Another form of Hyaluronic acid is Restylane, an FDA-approved non–animal-stabilized hyaluronic acid derivative used for soft tissue augmentation. Unlike Hylaform gel, it is derived from streptococcal bacterial fermentation and does not require an animal source. At 20 mg/mL, Restylane has a higher concentration of hyaluronic acid than Hylaform gel. It is used to treat wrinkles and scars and in lip augmentation. The use of synthetic microspheres is growing in popularity.
Synthetic fillers
As the name suggests, these fillers contain no biological compounds to provide their substantive or filling effects.
One product, Radiesse is composed of microspheres of calcium hydroxyl appetite suspended in an aqueous gel carrier. These biodegradable microspheres serve as a lattice upon which the body forms a scaffold for tissue infiltration.
The spheres degrade slowly over years for a longer-lasting, semi-permanent effect.
It’s use as a soft tissue filler is commonly for the nasolabial folds and marionette lines, although it is better known for more complex procedures such as bladder neck augmentation for urinary incontinence, vocal cord augmentation for paresis, and periodontal defects.
Another artificial filler, Reviderm intra, consists of 40- to 60-mm dextran beads suspended in hylan gel of nonanimal origin. The proposed mechanism of action is an initial macrophage response followed by fibroblast proliferation and new collagen formation. Intradermal injection is used to treat wrinkles and cutaneous defects (eg, atrophic scars), and, in the Netherlands, it is used in lip augmentation.
Sculptra (or New-Fill) is a non–animal-derived polylactic acid touted to be biocompatible, biodegradable, and immunologically inert. It serves as a volume enhancer and is injected either into the superficial dermis for the treatment of wrinkles and acne scars. Results are not immediate; treatment is performed as a series of 3-5 treatments.
Hybrid technologies
These products consist of artificial fillers such as polymethylmethacrylate microspheres suspended in bovine collagen. The role of the collagen in these products is to only serve as a vehicle for injection as it will eventually degrade, leaving behind a permanent implantation of the beads. The mixture is usually injected at the dermal-subdermal junction to treat deeper wrinkles and scars.
A quick reference guide to popular dermal fillers can be found here. Some of the types shown may not be available in all countries, and we provide it for a reference only.