2 Fillers
evolution, regression, and the future
Summary and Key Features
• The first pre-modern era filler was fat
• The first commercial modern era US Food and Drug Administration (FDA)-approved filler was bovine collagen
• The first non-commercial modern era non-FDA approved filler was silicone
• Collagen was offered in 0.5 mL and 1 mL syringes for correction of ‘two-dimensional’ problems, i.e. wrinkles, scars
• Collagen had two major problems: delayed hypersensitivity and brief duration
• The introduction of botulinum toxin eliminated dynamic movement as a cause of wrinkles and lines, and allowed true volume deficits to be appreciated
• The introduction of hyaluronic acid (HA) gel fillers from Europe was a game changer, initially because of duration of effect; other benefits were seen later
• With HAs, attention shifted from ‘two-dimensional’ to ‘three-dimensional’ problems, i.e. from lines and wrinkles to subcutaneous atrophy and fat loss
• Fillers that followed, e.g. polylactic acid, calcium hydroxylapatite, polymethylmethacrylate, focused more on host response and endogenous collagen production than true volume replacement, mimicking the phenomenon seen with micro-droplet silicone
• Almost all fillers in the foreseeable future are entering the USA from Europe
• Newer fillers seek ability to control length of duration, enhanced stimulation of dermal collagen, reversibility, and greater lift
Collagen (Zyderm®, Zyplast®, Cosmoderm®, Cosmoplast®, Evolence®)
Collagen is the most abundant protein in skin. Collagen implant material was first developed by four Stanford doctors in the early 1970s: Rodney Perkins, John Daniels, Edward Lock, and Terrence Knap. In 1977, they reported the successful injection of human-, rabbit-, and rat-derived collagen into subcutaneous tissue of rats. This successful experiment led them to try injecting the scars and depressions of volunteers with both human- and bovine-derived collagen. These volunteers had a 50–85% improvement that was sustained over 3–18 months. Following extensive clinical trials in the late 1970s, Zyderm®1 implant (35 mg/mL of solubilized collagen) was approved by the US Food and Drug administration in 1981 (Fig. 2.1A), and Zyderm®2 (65 mg/mL of solubilized collagen) was approved in 1983. Both products were a relatively non-viscous suspension that allowed for injection through a 30-gauge needle. Because 2–3% of treated patients developed localized allergic reactions associated with these injections, pre-treatment skin testing with 0.1 mL subcutaneous challenges was recommended prior to using the Zyderm® 1 and 2 implants.