Special Feature: Filler Retrospective

By Allie Anderson / 01 Aug 2015

From the conception of the earliest collagen-filled syringes through to the modern-day portfolio of injectables, Allie Anderson traces the development of the dermal filler

One of the most popular treatments offered in aesthetics clinics is the dermal filler. According to statistics from WhatClinic.com, more enquiries were made about dermal fillers in the UK in 2014 than any other non-surgical aesthetic procedure, and the number of filler treatments carried out increased by 131% last year alone.1 These days, it seems consumers are more willing than ever before to have substances injected into their faces to smooth the appearance of lines and wrinkles in the pursuit of eternal youth. However, this kind of procedure is not a recent advancement. Records of patients having fat removed from their arm and grafted to their face date back as far as the 1890s, and injectable fat grafts have been performed since the 1920s.2 Paraffin was used as a skin filler in the early part of the 20th century, when a Viennese surgeon developed the technique of injecting a product that becomes semi-liquid when heated and solidifies when it cools. The procedure was adopted for treating cosmetic indications – such as filling cheeks, augmenting breasts, nasal defects and facial wrinkles – but soon resulted in complications that rendered it unfit for purpose.3

The collagen era

Since the first modern-era dermal fillers were approved by the Food and Drug Administration (FDA) for cosmetic use in the US in 1981,4 the idea of using injectable substances to fill out and smooth wrinkles in the face has gradually become so commonplace, it’s almost part of modern-day collective conscious. But it wasn’t always that way. “The whole idea of injecting something into your face to make you look better was very alien back then,” explains aesthetic business consultant and Aesthetics editor Amanda Cameron. “It came to the UK a few years later, but the market was tiny and it was only available in little pockets, like London’s Harley Street, and parts of central and northern England.”
This first-generation filler was in the form of bovine collagen and was brought to the international marketplace by US-based Collagen Corporation. It became popular as an aesthetic treatment and in its most primitive form – branded Zyderm I – was found to be highly effective in minimising fine lines and shallow scars, with results lasting around three months. However, as a filler for deeper wrinkles, nasolabial folds and marionette lines, results were both less convincing and shorter lasting.5 So while overall demand for this procedure in UK clinics through the 1980s and 90s was comparatively small, patients who wanted a sustained result would have to return to have the treatment several times a year.

Working as a UK trainer for Collagen Corporation, Cameron witnessed first-hand how the UK market developed in those early years. “We were selling around 5-6,000 syringes a year, which isn’t a lot in the grand scheme of things, especially when you consider that they didn’t last long, so patients would have to have more than one,” she recalls. “For several years, we had a monopoly in a small market, so the only way to make money was to put the price up. It was unique, and people were prepared to pay for it.” Patients also had to undergo a skin test four weeks before the treatment, so it didn’t provide the instant gratification that consumers crave nowadays. Aesthetic nurse Marie Duckett, of Fiona and Marie Aesthetics, was introduced to dermal fillers when she, too, worked at Collagen Corporation’s UK arm, and began injecting when fillers were in their infancy. She remembers bovine collagen as “a nice product to use” – albeit with its disadvantages. “Apart from the fact that it didn’t last very long, a high percentage of patients were allergic,” Duckett comments. “There was a 3% allergy rate with bovine collagen, even among patients whose skin tests showed no allergic reaction. In terms of the hundreds of thousands of patients who walk into clinics today, that would be unacceptable.”

In addition, the high viscosity of the fillers meant they had to be injected through large-gauge devices (although, the needles used were no bigger than those used today) causing pain, bruising and swelling – and with no comparable alternative, patients had to tolerate it. A breakthrough came a few years later with the introduction of Zyderm II and Zyplast: the former is a similar preparation to Zyderm I, but with 65mg/ml rather than 35mg/ml of bovine collagen (with 0.3 per cent lidocaine), injected into the superficial dermis; while the latter contains the same 35mg/ml of collagen cross-linked with glutaraldehyde to form a more viscous substance that is more resistant to degradation, and therefore lasted longer. Zyplast was injected into the mid-dermis, and was especially effective in treating deep wrinkles and skin folds, atrophic scars and to define the vermillion border of the lips.6


Hyaluronic acid – a new dawn

Bovine collagen enjoyed a monopoly as a filler in the UK until the mid-1990s, when a new development was to revolutionise the market. A naturally occurring substance found in cell and tissue fluids, hyaluronic acid (HA) is a significant factor in keeping the skin moisturised.7 Since the skin’s high water content is partly responsible for the properties associated with young and youthful-looking skin – pliability, resilience and plumpness – the emergence of HA fillers was a significant advancement in the development of anti-ageing solutions, providing very effective results.8,9 First came Hylaform, a HA filler made from rooster combs that was gradually absorbed by the body. This was closely followed by Restylane, one of the first dermal fillers that wasn’t derived from animal sources. The new-style treatments could be used straight from the box and had a far lower reaction rate, thereby spelling the end for collagen fillers. “When Restylane suddenly appeared, it was a shock. It had a significant impact on the industry and took most of the collagen market overnight,” Cameron explains. “First, there wasn’t the same risk of allergies as with collagen fillers, and second, you didn’t have to have a skin test, so you could just walk in and, after a consultation, have the treatment there and then.”

HA fillers remain one of the primary treatments for the correction of wrinkles, folds and loss of volume that develop with age, and are a popular choice among practitioners and patients alike. However, scientific developments in the way HA fillers work together with how they are placed – have meant that for some, Restylane, which is now classed as one of the original HAs, isn’t always practitioners’ first choice of filler to use. “It had its place at the time, but it’s superseded by products with better advancements in biotechnology,” says Dr Raj Acquilla. He uses fillers containing Vycross technology, which combines 90% low- and 10% high-molecular-weight hyaluronic acid that enables better cross-linking. The result, says Dr Acquilla, is smoother and longer lasting with minimal swelling. Dr Kate Goldie explains that this cross-linking – whereby chains of molecules are bonded together – improves the functionality of the product. “The cross- linking process means the substance is able to integrate with the tissue unusually well. When the particles are cross-linked, they’re able to move into small spaces and the product blends. The other thing is that these gels are highly cohesive, so the molecules stay together. Low viscosity and high cohesivity equals a product that is constant in its result.”

 Other filler ingredients have been developed, each with varying degrees of permanence and with their own functionality. One example is Poly L lactic acid (PLLA), a semi-permanent filler belonging to the class of substances known as collagen stimulators. Rather than ‘fill’ wrinkles, folds and deflated areas directly, the injected material promotes the production and deposition of collagen where it is required in the face. Another biocompatible substance, calcium hydroxylapatite, contains small particles suspended in a water-based gel, which form a scaffold over which the collagen produced by the body can grow. Advancements of fillers since the early 2000s has resulted in products with varying degrees of thickness, which determines how deeply the substances can be injected, and hence, their indications. “This has changed placement of fillers tremendously,” comments Dr Ravi Jain. “Most of the fillers I perform are either on the bone, under the muscle or in the fat – anywhere but the dermis.” As such, it is now considered by many to be a misnomer to refer to these treatments as ‘dermal’ fillers, but rather ‘soft tissue’ fillers. Dr Goldie goes further, suggesting that the word ‘filler’ is “misleading” when describing modern-day products. “The way fillers are going now, they have the ability to do lots of things. It’s not just about occupying a space, it’s about becoming part of the tissue,” she says. “We want the product to occupy space, but we also want them to make the tissues lie in a smooth, even way, as well as to volumise. Practitioners used to use volumisers superperiosteally, but the modern gels can be used subdermally as well.”

Great knowledge, great responsibility

The evolution of dermal fillers has also had a significant impact on both the level of skill and the knowledge required to be able to inject them competently. Training in injectables has historically been somewhat hit and miss, with many practitioners having only been required to undertake the bare minimum before being let loose with a syringe. “In the early days, we were mainly training doctors and plastic surgeons, so they already had a strong core knowledge of anatomy and physiology, but they needed guidance in filler placement,” Cameron recalls. “Now, people are coming in to the industry from different backgrounds, so the entry level knowledge is very different.” The reclassification of fillers from prescription-only medications (POMs) to ‘medical devices’ under the Medical Devices Directive has opened up the market to practitioners from non-medical backgrounds, further increasing the need for more in-depth training.

Arguably, one of the biggest changes in fillers within the last 20 years has not been developments in products themselves, but in the level of anatomical knowledge required to be able to use them most effectively. “We knew absolutely nothing; we looked at the face in a 2D approach, so when we placed a needle into the skin exactly, we didn’t understand what depths certain structures were located,” says Dr Acquilla. “We were causing risk and unnecessary side effects to the patient. We were also not injecting at the right level for optimum effect and best results, which were pretty primitive.” With training gradually incorporating more advanced understanding of facial anatomy and physiology – and focusing on a three-dimensional approach to injecting – practitioners are employing more refined techniques and generating better results for the patient. “Anyone who’s injecting nowadays should have a knowledge of where the needle tip is to the nearest 1mm3 in the face, and what that structure represents,” Dr Acquilla adds. “Placement and technique are paramount; absolute accuracy and precision dictates the result and the safety of the treatment.”

Complementary treatments

Just as fillers and their ingredients have evolved over time, so have other, related treatments – as well as consumers’ attitude towards aesthetic procedures in general – which have impacted both the use of fillers and the results that are achievable. “With the advent of technology, we now have more advanced lasers and skin tightening and lifting treatments,” explains Dr Tracey Mountford. “The effect is that we have a more extensive portfolio of products to call upon, which yields much better results. I don’t believe these other treatments have affected our use of fillers in terms of numbers, but they have certainly made dermal fillers look better, as we are delivering a total package.” Dr Linda Eve likens the practitioner’s choice of different, complementary treatments to artistry. “We’re much more into combination therapy now. We’re artists; we have many colours on our palette of paint and we have many products in our toolbox,” she says. “We can safely mix and match products from different companies these days. For example, we may use PLLA to give a contoured scaffold lift to the face, then use the HA filler to address the nasolabial lines or marionette lines. You can use more products, with confidence, to get lift and shaping that you want to achieve.”

With training gradually incorporating more advanced understanding of facial anatomy and physiology – and focusing on a three-dimensional approach to injecting – practitioners are employing more refined techniques and generating better results for the patient

As Duckett points out, equipment has also undergone development since the advent of the first collagen filler, which has in turn had an effect on the injector’s technique. “New technology has come about with needles. You can pick up a standard 30-gauge needle where the outer diameter of the needle is 30-gauge, but another 30-gauge needle will have the same outer diameter, but the inner bore is larger,” she comments. “So as you push the plunger, there is less resistance. Wide bore needles have come about in the last four or five years, and that has been a big breakthrough; it’s more comfortable for the patient as well.” She adds that ergonomics also come into play, when it comes to syringes, “The distance from the flanges to the end of the plunger can be longer in one 1cc syringe than another, making it more difficult to inject.” With needles becoming ever-thinner and syringes more ergonomically pleasing, the filler experience is much improved both for the patient and for the practitioner.

Botulinum toxin – a game changer

Back in the late 1980s when collagen fillers were a dominant force in an as-yet largely unchartered industry, a discovery was about to be unearthed that would later be described as “one of the most successful symbioses in late-20th century cosmetic medicine”.10 Having been successfully used to treat blepharospasm (eye twitching) and strabismus (squinting), a dilution of botulinum toxin injected into muscles around the eyes was found to have the unusual side effect of smoothing fine lines and wrinkles. Several years of studies and trials followed before the cosmetic and aesthetic worlds began to realise the benefits of what soon became widely known by its brand name Botox, and consumers became drawn to this new treatment. 

Although Botox was only granted approval for the treatment of glabellar lines in 200211 – and for crows’ feet as recently as 201312 – practitioners across the world had been performing the procedure ‘off-label’ for years. As well as having a strong media presence, which hadn’t been seen before in the aesthetics industry, many users reported that with botulinum toxin they were able to produce more desirable treatment outcomes. As such, it had a significant impact on the industry as a whole, as well as the filler market. Cameron suggests that in the year-long period botulinum toxin began appearing in UK clinics, the aesthetics industry more or less doubled in size. “Things changed dramatically. The PR botulinum toxin had was phenomenal, and at around the same time it became fashionable to have cosmetic treatments,” she recalls.

Dr Jain concurs that as it became more available and accepted, it had the knock-on effect of opening up aesthetic medicine to wider audiences. “Today, I would say that botulinum toxin is probably the first thing people come into my clinic for, with fillers second.” Unlike dermal fillers, the formulation of botulinum toxin has changed little over the years, and its effects have similarly remained constant. However, some practitioners report that demand for the treatment fluctuates depending on trends. “Sometimes, it’s really on everyone’s lips and then interest fades away again,” comments Duckett. “Every now and then there seems to be a flurry of patients who are tired of the ‘Botox look’ and want to look less frozen, so they go back to the fillers again.” Notwithstanding, the global botulinum toxin market is expected to be worth almost $3bn in just three years’ time.13

Driving change in fillers

The evolution of filler treatments can be attributed to a number of influences, a significant factor being the way we understand the ageing process and its effects on the appearance of the skin. “Going back 18 years, you didn’t inject the body of the lip, you only did the lip border. You mainly treated lipstick lines, nasolabial lines, marionette lines, perioral lines, periorbital lines and frown lines,” says Duckett. “Now, we still treat lines and wrinkles but we also look at volume. That has been one of the biggest changes – the recognition that lines and wrinkles occur because the face becomes like a slowly deflating balloon over time; that volume is lacking and you need to restore the volume in order to restore the proportions and take the pressure off lines and wrinkles.” 

From the early days of ‘chasing lines’ with collagen fillers, and as understanding of the anatomical structures underlying injection sites developed, so did the substances used and the devices through which they were delivered. “Consumers and patients know what aesthetic result they want – usually that means a procedure that gives a natural-looking and un-spottable look,” says Dr Eve. “Now, practitioners are innovating more in how to use dermal fillers, and they go to the companies and say ‘I need something that can do this and has these specific properties’, and that feeds back into the system. We’re also getting really good research and development in the companies who understand and can achieve products that are much more compatible with the results the patients want.” 

As such, developments thus far, and those that are yet to occur, are brought about by close working between progressive injectors and state-of- the-art manufacturing. “That’s how you get really clever products,” Dr Eve adds. The popularity of injectable treatments shows no signs of ebbing in the coming years, as long as it remains a comparatively affordable option. Raw material prices have seemingly plateaued, having changed only marginally in the 30-or-so years since collagen fillers emerged – a consequence of the ever-expanding and competitive market. But the price to the consumer has, in many clinics, risen to reflect the advanced skills and knowledge of the practitioner and the improved results that fillers can now achieve. “The results that I could give 15 years ago deserved the low prices fillers were being charged at,” comments Dr Acquilla. “But the results we can now generate, because of our understanding of anatomy and the technical application, as well as the sophisticated science of the products we inject, are so superior that the value of that to the patient is disproportionately higher than it used to be.” Cost implications aside, Cameron believes we’ve reached a point where we can offer optimum product choice for optimum effects, for lifting, volumising and filling. “The next big milestone will be if someone manages to do all this without using a needle,” she concludes, “but I think that’s a long way off.” 

References

  1. WhatClinic.com, Thread lifts’ revealed as top cosmetic trend of 2014, while ‘fat filler’ destined to be big in 2015, (Ireland: WhatClinic.com, 2014) http://www.whatclinic.com/about/press/
  2. Hendy Amgad, ‘Facial Re-Contouring Using Autologous Fat Transfer’, J Plast Reconstr Surg, 34(1) (2010), pp. 65-69
  3. J Glicenstein, ‘The first ‘fillers’, Vaseline and paraffin. From miracle to disaster’, Ann Chir Plast Esthet, 52(2) (2007), pp. 157-61.
  4. K Cockerham and VJ Hsu, ‘Collagen-based dermal fillers: past, present, future’, Facial Plast Surg, 25(2) (2009) pp. 106-13
  5. Dr Robert S Bader, Dermal Fillers: Overview, (US: Medscape, 2015), http://emedicine.medscape.com/article/1125066-overview
  6. Dr Robert S Bader, Dermal Fillers: Collagen, (US: Medscape, 2015), http://emedicine.medscape.com/article/1125066-overview#a2
  7. E Papakonstantinou et al, ‘Hyaluronic acid: A key molecule in skin aging’, Dermatoendocrinol, 4(3) (2012) pp. 253–258
  8. MP Lupo, ‘Hyaluronic acid fillers in facial rejuvenation’, Semin Cutan Med Surg, 25(3) (2006), pp. 122-6
  9. H Sundaram et al, ‘Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications’, Plast Reconstr Surg 132 (2013)
  10. Katherine Ashenburg, The birth of Botox, (Canada: Reader’s Digest, 2011), http://www.readersdigest.ca/health/beauty/birth-botox/#R6Byf58CjaMh1S8B.97
  11. Allergan, Botox history and development, (UK: Allergan Inc., 2010), http://www.allergan.jp/Assets/pdf/botox_history_and_development.pdf
  12. Marie-Louise Olson, Doctors have been doing it ‘off the books’ for years but now they finally have the go-ahead to inject BOTOX into those unwanted ‘crow’s feet’ wrinkles, (UK: Daily Mail, 2013) http://www.dailymail.co.uk/news/article-2418738/Botox-legally-approved-lines-wrinkles- crows-feet-despite-Drs-doing-years.html
  13. Eva Wiseman, Is Botox starting to show its age?(UK:TheGuardian,2014), http://www.theguardian.com/lifeandstyle/2014/mar/23/botox-starting-to-show-age-eva-wiseman

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