This article was commissioned by Allergan Aesthetics, though the content therein is based on Dr Marshall Murdoch’s professional experience and opinion. For more information on the product, please ask your doctor.
The second most performed aesthetic procedure on the planet (after botulinum toxin) remains shrouded in mystery and misinformation1. Dr Marshall Murdoch “fills” us in…
A (very) brief history of ‘filler’
After the invention of the hypodermic needle by Mitchell & Gillespie in 1896, medical doctors soon used it for soft tissue filler injections2,3. Gersuny reported the first medical injection of liquid paraffin in 1900, which, over the course of a decade, became commonly used for facial filling.
However, it soon became apparent that paraffin was poor filler material as, by 1912, many severe complications were being reported.
Fast-forward to post-World War II
During this period, Japanese medical doctors used US Army stocks of industrial liquid silicone for injectable breast augmentation.
Soon after, US medical doctors published laboratory and clinical trials on liquid silicone, all reporting very promising outcomes. Despite initial positive feedback, severe complications later ensued – which ultimately resulted in a statutory ban on silicone injections, starting in 19752,3.
It was evident that a more ‘natural substance’ was needed. This concept subsequently led to research being conducted into the use of injectable collagen from cows, which was first conducted in the 1970s. Collagen fillers were approved by the FDA in 1981 and, although they had much lower complication rates, they remained far from ideal.
And so the search continued3
Drs Balazs & Denlinger published the first use of hyaluronic acid for soft tissue filling in 1989.
However, the hyaluronic acid (HA) revolution was truly started by Swedish scientist Dr Bengt Ågerup. He created the first nonanimal stabilised hyaluronic acid – a material he patented as NASHA™.
It was clinically branded and launched in 19962,3. Since then, the continued improvement in gel technology and safety have only served to enhance the popularity of HA as a filler, with more than 130 brands being available worldwide2,3,4.
Properties of an ideal filler
The ideal filler should be safe, effective, convenient and affordable. Durability with reversibility is highly desirable from a medical doctor’s point of view – along with ease of injection. Patients desire a natural
look and feel, with minimal pain, swelling and bruising to prevent downtime. There is no current material that can completely satisfy all the above requirements, but the material that has come closest is hyaluronic acid5.
What is HA?
Hyaluronic acid (HA), also called hyaluronan, is part of a group of tissue compounds called glycosamino-glycans (GAGs for short, not fun!). These are combinations of amino acids and carbohydrates that are found in long molecular chains (polymers), and consist of hundreds to thousands of repeating basic units (much like carriages of a train)6,7.
The basic molecule of HA is a small two-piece compound of D-glucuronic acid and N-acetyl-D-glucosamine. When this is dissolved in water, it forms chains, causing the solution to become thicker and gel-like.
HA has an enormous affinity for water – so much so that it has been reported to be capable in ‘gelling’ 100 to 1 000 times its weight in water5,6.
Natural HA is made and secreted by cells in the skin (which accounts for half the HA in the human body), and is also found in other soft tissues. Intriguingly, HA is identical across all mammalian and avian species. This discovery led to the first development of HA gel obtained from the combs of roosters. Ultimately, for improved safety, as well as required volumes, all modern HA is laboratory made5,6.
While basic lab-made HA is 100% nature identical, it is important to note that natural tissue HA stays in the tissue for a very short time before it is turned over. It is secreted and degraded by the cells in less than one day.
This means that if nature-identical HA were to be injected, the clinical effects would also only last for a few days5,6. Obviously, patients would be less than impressed if this happened!
To improve the resistance of injected filler to degradation, it undergoes a series of reactions called cross-linking, where a small organic compound is used to bond the chains together. Crosslinking increases both the gel’s viscosity as well as its lifetime in the injected tissue.
So instead of staying for a day or two, injected HA can remain for up to 24 months. It also means that while clinically used HA is tissue compatible, it is no longer 100% nature-identical. This is one of the suspected reasons for rare but well-known reactions5,6.
Some of the first non-animal gels to be used clinically were made by passing a mixture of cross-linked HA though different sized meshes to obtain various (microscopic) sized ‘chunks’. These particles of HA were then suspended in a much thinner HA solution to allow for them to be injected.
The result was a biphasic mixture – a sort of biological chowder! Later, gels that had the same consistency throughout were manufactured, resulting in monophasic gel. These are the bio-equivalent of a smoothie2,3,4,5,6!
For the people in white coats…
The physical properties of an HA gel are explained in the complex field of rheology. The most important rheological properties are G’ (G Prime) and Cohesivity7,8.
These properties interact with the tissues to create the clinical properties known as lift capacity and longevity7,8. Different fillers are made with varying concentrations of HA, as well as to manufacturers’ proprietary recipes. The process of manufacture significantly changes the properties of the gel – just as bakers may use the same basic ingredients yet have wildly varying cakes!
G’ (G Prime)
G’ is the scientific abbreviation for modulus of rigidity. It describes an object’s tendency to bend when acted upon by opposing shearing forces.
Imagine a branch of hardwood and a branch of green wood of the same size and thickness. When you apply the same force to each one, the green branch may bend a lot, while the hardwood branch bends very little.
This means that hardwood has a high G’, while green branches have a lower G’. High G’ fillers are stiffer in the tissues (and may be more easily felt by the patient), but they tend to have higher lift capacity too7,8.
Cohesivity
Cohesivity describes the gel’s resistance to breaking apart when compressed. Highly cohesive fillers stick together as a single ‘blob’, whereas less cohesive fillers break apart into smaller pieces. This is important during facial animation and plays a role in lift capacity as well. The monophasic fillers tend to have better cohesivity7,8.
Longevity
In human tissues, HA is broken down by two pathways: enzymes and free radicals. There are six different kinds of enzymes that dissolve HA in human tissues – all of which are key in helping the body break down and turn over HA. Genetic variations in these enzymes may be partly responsible for the variable effect of filler in some patients. As injected HA has been chemically modified, it is far more resistant to enzyme degradation than natural HA. Free radicals are also responsible for breaking down both natural and injected HA.
The amount of tissue antioxidants controls the free radical levels. This may explain why a patient’s lifestyle factors (smoking, exercise and diet) may influence the longevity of their results7,8.
Conclusion
HA is close to the ideal filler, and continued improvements have enhanced both safety and popularity. While unexpected reactions continue to occur (as they do for all other fillers), the underlying biological reasons remain an area of active research. Perhaps the most reassuring factor is the temporary nature of HA. As Professor Koen De Boulle has so eloquently stated, “If you use a permanent filler, and you encounter a problem, you can be certain that the problem, too, will be permanent.”
*Please note that fillers are considered scheduled medical devices; we are therefore unable to publish product/brand names in adherence to medical rules and regulations. Should you wish to know more about various filler products available, kindly contact your doctor.
This article was sponsored by Allergan Aesthetics, though the content therein is based on Dr Murdoch’s’ professional experience and opinion.
References:
- Global Aesthetics Consensus: Botulinum Toxin Type A- Evidence-Based Review, Emerging Concepts, and Consensus Recommendations for Aesthetic Use, Including Updates on Complications. Sundaram H, Signorini M, Liew S, et al. Plast Reconstr Surg. 2016;137(3):518e-529e. doi:10.1097/01.prs.0000475758.63709.23
- The history of injectable facial fillers. Kontis, TC and Rivkin, A. Facial Plast Surg. 2009 May;25(2):67-72
- Hyaluronic acid fillers: history and overview. Kim, J and Sykes JM. Facial Plast Surg. 2011 Dec;27(6):523-8
- History of Dermal and Subdermal Injectable Fillers Before Collagen: The Early Years. Memar, O. J Skin Stem Cell. 2020 March; 7(1):e104559.
- Hyaluronic acid: A key molecule in skin aging. Papakonstantinou, E. et al. Dermatoendocrinol. 2012 Jul 1; 4(3): 253–258.
- Hyaluronan (Hyaluronic Acid): a natural moisturizer for skin care September 2015. ŠMejkalová, D and Angeles, GH. In book: Harry’s 9th Edition (pp.605-622) Edition: 9th, Vol 2. Part 4.1.3 Chapter: Hyaluronan: A Natural Moisturizer for Skin Care Publisher: Chemical Publishing Company. Ed: Chia Wen Chen
- Clinical uses of hyaluronan. Balazs EA and Denlinger JL. Ciba Found Symp. 1989;143:265-75; discussion 275-80, 281-5.
- Use of hyaluronic acid fillers for the treatment of the aging face. Gold, MH. Clin Interv Aging. 2007 Sep; 2(3): 369–376
Disclaimer: This article is published for information purposes only and should not be regarded as a replacement for sound medical advice.
I am a Plastic and Reconstructive Surgeon in Private Practice. My practice is located at the Knysna Advanced Healthcare Medical Centre, a modern day-hospital in the beautiful Southern Cape town of Knysna. In addition, I am one of the Local Country Mentors for Facial Aesthetics.