A history of innovation, mistakes and some important lessons.
From liquid paraffin wax injections to modern hyaluronic acid fillers.
Dermal fillers are sometimes regarded as a recent development in aesthetic medicine. In reality, doctors have been experimenting with injectable substances to restore facial volume and improve appearance for well over a century.
Some of those early treatments were remarkably inventive. Unfortunately, others were remarkably dangerous.
The history of dermal fillers is a fascinating story of medical innovation, changing fashions and the gradual recognition that what appears safe and effective today may not necessarily remain so in the years ahead.
It is also a history that I have witnessed part of myself, having started practising aesthetic medicine in the last days of collagen fillers, as they gave way to a new generation of hyaluronic acid products.
In the beginning: liquid paraffin wax and the search for a permanent filler
The story begins as far back as the late nineteenth century.
In the 1890s, doctors began experimenting with injections of liquid paraffin wax to correct facial defects and restore lost volume. The Austrian surgeon Robert Gersuny is generally credited with pioneering its use.
The attraction was understandable. Paraffin was inexpensive, readily available and appeared to offer a permanent correction.
Unfortunately, permanence turned out to be one of its greatest disadvantages.
Over time, many patients developed complications. These included inflammation, hard lumps known as paraffinomas, migration of the injected material and, occasionally, severe tissue damage, with some complications appearing years after the original injections.
Silicone: another attempt at permanence
During the twentieth century, liquid silicone emerged as another potential solution.
It was particularly attractive because it could produce relatively predictable volume enhancement without being absorbed by the body.
However, as experience accumulated, reports emerged of chronic inflammation, granulomas, migration and tissue distortion. Some patients experienced serious complications many years after treatment.
Silicone injections also became associated with the use of inappropriate or industrial-grade materials, sometimes administered by inadequately trained practitioners.
In 2002 the actress Leslie Ash had liquid silicone injected into her lip. This resulted in significant and permanent swelling and much attention from the tabloid press.
Medical-grade silicone has continued to have very limited applications in some settings, but its history as a cosmetic injectable illustrates a recurring problem.
A filler that produces a satisfactory result today is not necessarily a filler that will remain trouble-free indefinitely. Both paraffin an silicone were lessons in the difference between achieving an immediate cosmetic improvement and establishing long-term safety.
Collagen: the beginning of modern dermal fillers
A major change occurred in the early 1980s with the introduction of injectable bovine collagen. Unlike paraffin and silicone, collagen was a naturally occurring protein, although the products were derived from cows rather than human tissue.
Zyderm became the first collagen filler approved by the US Food and Drug Administration for cosmetic use in 1981.
Collagen offered a more biologically compatible and temporary alternative to permanent injectable materials.
For the first time, doctors had access to a commercially manufactured, standardised injectable filler specifically developed for correcting facial lines and wrinkles.
But there were disadvantages. Because bovine collagen could provoke allergic reactions, patients required skin testing before treatment. Depending on the product and protocol, this could involve two small test injections several weeks before the actual treatment.
The results were also relatively short-lived, and repeated treatments were necessary.
My introduction to dermal fillers
When I began practising aesthetic medicine, collagen fillers were still in use.
I had colleagues who used them and spoke highly of the results. However, the requirement for preliminary allergy testing made treatment inconvenient for both doctor and patient.
By the time I began offering dermal fillers myself, a new product had arrived namely Restylane. It was the first dermal filler I used.
Within a few years of Restylane's introduction, bovine collagen had largely disappeared from routine aesthetic practice.
Looking back, I had entered aesthetic medicine at a particularly interesting turning point.
Restylane and the hyaluronic acid revolution
In 1996, the Swedish company Q-Med introduced Restylane, developed under the leadership of its founder, the scientist and entrepreneur Bengt Ågerup.
Restylane was the world's first non-animal stabilised hyaluronic acid (NASHA) dermal filler.
Hyaluronic acid is a naturally occurring substance found throughout the body, including the skin, where it plays an important role in hydration and tissue structure.
The challenge was that unmodified, natural hyaluronic acid is broken down relatively quickly in the body.
Ågerup's achievement was to develop a commercially successful stabilised hyaluronic acid gel using cross-linking technology. Cross-linking creates connections between HA molecules, making the gel more resistant to degradation and allowing it to provide a longer-lasting correction.
Hylaform: another early hyaluronic acid filler
Restylane was not the only hyaluronic acid filler to emerge during this period.
Hylaform, developed by the American company Biomatrix, was also introduced in Europe in 1996.
Unlike Restylane, which used hyaluronic acid produced by bacterial fermentation, Hylaform was derived from an animal source, specifically chicken (rooster) combs. It was subsequently approved in the United States in 2004.
Hylaform generally produced shorter-lasting results than some of the newer HA fillers and gradually lost favour as more sophisticated products became available.
The arrival of these early HA fillers marked a major advance over bovine collagen. Routine allergy testing was no longer required, results were more predictable, and the range of possible facial treatments expanded considerably.
Other manufacturers soon introduced their own products, with differences in HA concentration, cross-linking, gel structure and physical properties. The modern dermal filler industry had arrived.
The importance of reversibility
One of the most important advantages of hyaluronic acid fillers became increasingly apparent as clinical experience developed.
Hyaluronic acid can be broken down using an injectable enzyme called hyaluronidase, initially available under the brand name Hyalase.
This means that unwanted filler can be dissolved, although the process is not always completely predictable.
Hyaluronidase also has an important role in the management of certain complications, particularly vascular compromise.
This does not make hyaluronic acid fillers risk-free, but reversibility represents a significant advantage over permanent injectable materials.
Polyacrylamide: a recurrent problem returns
Despite the growing popularity of temporary hyaluronic acid fillers, the search for a permanent injectable material continued.
During the 1990s and 2000s, synthetic polymer hydrogels became available under brand names including Aquamid and Bio-Alcamid.
Both were intended to provide long-lasting soft-tissue augmentation without the need for repeated treatments.
Initially, these products appeared promising. They were soft, injectable and capable of producing substantial volume enhancement.
Unfortunately, significant complications subsequently emerged.
These included delayed inflammatory reactions, infections, migration and the formation of nodules or larger inflammatory masses. Some complications developed many years after the original treatment.
Removing these materials proved to be very difficult, even with surgical intervention.
Their use extended across several international markets, and surgeons continue to encounter patients presenting with complications from injections performed many years earlier.
Once again, the history of dermal fillers demonstrated that a permanent result could become a permanent problem.
Novabel: when natural didn't mean safe
Another particularly instructive episode occurred in 2010 with the introduction of the dermal filler Novabel.
Novabel was made from alginate, a naturally occurring polysaccharide extracted from brown seaweed. Its natural origins were an attractive selling point.
At the time, the manufacturer’s promotion stated “Sourced from nature, perfected by science. Sourced from natural marine algae extract, Novabel has been further perfected in the laboratory using a patented technology that gives you a pure and natural treatment that lasts.”
I remember the enthusiasm surrounding its introduction, although I was sceptical of the emphasis placed on it being 'natural'. As I remarked at the time, horse dung is natural too; but that doesn't mean I would want it injected into my face!
Unfortunately, Novabel's commercial life was remarkably short.
Within a few months of its introduction, reports emerged of inflammatory nodules and foreign-body granulomas, particularly following treatment around the eyes. I was relieved that I never tried Novabel.
In July 2010, practitioners were advised to stop using the product. The UK Medicines and Healthcare products Regulatory Agency subsequently issued a safety alert, and Novabel was withdrawn.
And it demonstrated an important principle: the natural, biological origin of a substance tells us very little, on its own, about its safety when injected into human tissue.
Beyond Filling: the arrival of Biostimulation
The development of dermal fillers did not stop with hyaluronic acid.
In 1999, poly-L-lactic acid was introduced in Europe under the name New-Fill, later becoming better known as Sculptra.
Rather than simply replacing lost volume with an injected gel, Sculptra works by stimulating the body's own collagen production. Its effects develop gradually over several months.
Early experience was not without complications, particularly the development of papules and nodules. However, refinements in preparation, injection technique and patient selection have improved significantly its safety profile.
Other products followed, including calcium hydroxylapatite, marketed as Radiesse.
Today, Biostimulation is one of the most frequently discussed developments in aesthetic medicine. Yet the concept is far from new. Sculptra has been in clinical use for more than 25 years; a useful reminder that some supposedly modern approaches have a much longer history than we might imagine.
Have Dermal Fillers Become Safer?
In very many respects, yes.
Modern manufacturing standards, improved filler formulations and a better understanding of facial anatomy have all contributed to safer and more predictable treatments.
However, in an increasingly crowded dermal filler market we need increasing vigilance when sorting the good from bad. Particularly when government oversight is not as thorough as we might hope. Read Why Are There Over 140 Different Dermal Filler Products Licensed In The UK & EU but only 25 in the USA?
The development of hyaluronic acid fillers, with the possibility of dissolving unwanted material, was particularly important. However, no injectable filler is entirely without risk. Serious complications, including vascular occlusion, remain possible.
We discuss these in more detail in our article Are Dermal Fillers Safe?
The important point is that advances in product technology do not remove the need for clinical expertise, careful patient selection and appropriate injection technique.
Summary: what have we learnt from 125 years of experience
Looking back over the history of dermal fillers, several lessons stand out.
The first is that permanence is not necessarily an advantage. Some of the earliest injectable treatments were designed to produce permanent results. Their complications demonstrated why a substance that remains in the tissues indefinitely may create problems that are exceptionally difficult to correct.
The second is that long-term clinical experience matters. New products are generally introduced with encouraging clinical studies. But uncommon complications, delayed reactions and limitations in real-world use may only become apparent after many thousands of treatments and several years of follow-up.
The third is that innovation does not always mean improvement. Some genuinely important advances have transformed aesthetic medicine. The introduction of stabilised hyaluronic acid was one of them. Other innovations have offered more modest benefits, despite considerable initial enthusiasm.
And finally, the choice of practitioner remains as important as the choice of product.
Even an otherwise excellent dermal filler used inappropriately can produce a poor result. An experienced doctor using a well-established product, with a clear understanding of its limitations, will achieve a considerably better outcome.
History suggests that we should welcome innovation but not confuse novelty with progress. Afte 25 years in aesthetic medicine, I have seen products arrive with great enthusiasm, others quietly disappear, and a smaller number establish themselves through consistent clinical performance.
Perhaps the most important lesson from 125 years of dermal fillers is that good aesthetic medicine is not simply about what we can inject.
It is about knowing what to inject, where, how much and whether we should inject anything at all.
For a related discussion of how new aesthetic treatments are introduced and promoted, see Why Does Every New Treatment Start as a Miracle?
References
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Cockerham K, Hsu VJ. Collagen-based dermal fillers: past, present, future.
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Monheit GD. Hylaform: a new hyaluronic acid filler.
Facial Plastic Surgery. 2004;20(2):153–155.
Polyacrylamide Hydrogel Differences: Getting Rid of the Confusion.
Journal of Drugs in Dermatology. 2011;10(12):1370–1375.
André P, Moulonguet I. Alginate (Novabel): A New Class of Injectable Filler
Facial Plastic Surgery. 2014;30(6):644–646.