Understanding the history and science behind Hyaluronic Acid fillers can help you to decide which ones to use in your practice.

Hyaluronic Acid Fillers (HA) have been with us for over 20 years now and in that time a lot has changed but many other things have remained the same. This short article aims to give you a snapshot of their history, present and possible future.

The perfect gel is one that provides good flow, enough lift to produce an aesthetic effect and reduced hydrophilic nature



Before HA we had Collagen!

Yep, Collagen either from Cow, Pig or human. Collagen was first used in medical aesthetics in the 1980s, it was sourced from animal sources initially but eventually, we had a human source with products like Zyplast. It required a patch test before it was used in a patient to gauge any allergic reaction and when it was injected it only lasted a few months as it created a foreign body reaction. Collagen was mostly injected into the lips as it was a soft product with good flow

While collagen was growing in popularity a Swedish scientist started working with a new substance called Hyaluronic Acid and in 1995 he launched a HA filler with NASHA technology. This new product promised to provide longer duration and no patch test as it was an endogenous substance. Not long after this product was released, we saw an avalanche of products arrived, currently in Europe there are over 100 HA fillers available.

The arrival of HA fillers allowed patients to experience the lifting and filling effect for longer with limited adverse events – this helped the market to grow quickly and the number of injectors seeing a great opportunity grow too.

With the explosion in HA fillers it’s more important than ever to understand the differences between them and the impact they have on your product selection.



Rheology is defined as ‘the branch of physics that deals with the deformation and flow of matter, especially the non-Newtonian flow of liquids and the plastic flow of solids.’ In lay terms, rheology involves the study of liquids and how they ‘flow’ as well as how solids are ‘deformed’. It describes the “viscoelastic” properties of a material and explains how it can be measured.Rheological studies have become popular when analysing HA dermal fillers as they have to deal with many stresses in the skin.

Rheological studies often refer to key measurements which can be used by the practitioner to compare and contrast, below we describe the main measurements;

  • Elastic Modulus (G’) often referred to as G Prime this measurement describes the ability to recover the original shape after shear force is applied. A highly elastic HA gel will have low lifting capacity but be easy to extrude through a thin needle and provide long residence in highly mobile areas of the face.
  • Viscous Modulus (G”) describes the ability of a material to withstand shear force. A highly viscous HA gel will have high lifting capacity as it can withstand the weight of tissues around it but will be harder to extrude through a needle. Highly viscous gels usually have low elasticity and are better placed in deeper, less mobile tissues
  • Complex modulus (G*) The total ability of a material to withstand deformation. It is defined as the sum of the elastic modulus (G’) and viscous modulus (G”).
  • Cohesivity is defined as the ability for material not to disassociate due to high affinity between molecules. Highly cohesive gels maintain their position and integrity but will not integrate into the surrounding tissues, they are best suited for deeper tissues i.e. on bone. A gel with low cohesivity can break apart in the tissues and is best suited for superficial injection where a smooth, integrated approach is needed.


How does this affect my practice?

Now that we understand the measurements used to explain differences between HA fillers we can begin to explain how the manufacturing impacts rheology. Below are two key features of producing an HA filler; cross-linking and HA concentration

1. Cross-linking

Native HA is continuously consumed by the body via enzymes (hyaluronidases) if we were to inject HA without a way of stabilising the chains, we could expect duration to be around 24-48hrs. During the manufacturing process, a ‘stabiliser’ or cross-linking agent is added to the HA, this agent fuses the HA chains to each other at multiple points, when the gel is injected our naturally occurring enzymes struggle to degrade the gel as the cross-linker prevents the breakdown, thereby increasing the duration of effect or residence time. The vast majority of manufacturers use a crosslinker called “BDDE” (1,4-Butanediol Diglycidyl Ether) which is a chemical ester and considered to be non-toxic at the low levels used in HA gels but recent studies have shown this might be incorrect.

Different manufacturers use different percentages of BBDE in their products, usually higher cross-linked % mean longer durations but also a stiffer gel as the cross-linkers resist movement – gels with higher BDDE concentrations are also harder to remove using hyaluronidase if the patient or injector is unhappy with the result. In general, you should look for a gel that uses less than 3-4% BDDE.

Some HA gels exist on the market without BDDE, these gels are used for very superficial, skin rejuvenation purposes with the aim of ‘hydrating’ the dermis.

The key to choosing a filler based on cross-linking is to find the lowest % of BDDE that maintains a stabilised gel. Be careful with any company claiming under 3% as this is the minimum amount needed.

2. HA concentration

Increasing the amount of HA will increase the HA concentration in the final gel, HA concentration contributes to two main factors;

  1. Gel strength and Duration: As the HA concentration increases the space between each chain reduces, they become more compact and therefore the gel strength increases, as there is more HA to degrade the duration of action also increases. HA concentrations range between 15-30%. Generally, the ‘softer’ gels have a lower HA concentration (16-22%) while the ‘stronger’ gels have above 22%
  2. Hydroscopic nature: As HA is naturally a hydrophilic substance, we see products swell when introduced to water, the water binds to the HA chains and the product increases in volume – the same exists after injecting into the skin. Usually, we see significant swelling up to 2 weeks after injecting – once an equilibrium is achieved the gel cannot accept more water. HA concentration is the primary factor in how much the gel will swell, the higher the concentration the more swelling we will see. Swelling can provide some benefits (e.g. higher projection or lift) however, it can expand the area between each HA chain reducing cohesivity and softening the gel



As you can see there is a lot to learn about HA fillers and when choosing a product its important to ensure your company rep explains their range and how they can be used safely and effectively.