Peer to Peer
Hyaluronic acids
Our panel discuss hyaluronic acid technology, whether all fillers are particulate and the causes of inflammatory reaction following injection
Our panel this session comprises: Dr Laurence Hermitte, a biochemist engineer and managing director of Keysan Consulting. At Anteis, she was involved in the development of CPM technology for their Belotero hyaluronic acid range; Dr Stefanie Williams, a consultant dermatologist. She is also founder and medical director of European Dermatology London, based in Harley Street and Chelsea Bridge; Mr Peter Sharma, a consultant NHS surgeon and medical director for Cambridge Medical Aesthetics Ltd; Dr Alain Lajeunie, a mesotherapist and aesthetic practitioner who has provided training in both since 1999; Dr Chantal Belin, a quality and regulatory support manager for Symatese Research & Development; and Dr Martyn King, a cosmetic physician and owner of Cosmedic Skin Clinic in Birmingham
Q:
If all HAs are particulate, how does this work with cohesive polydensified technology which creates a more uniformed, elastic polymer?
Dr Laurence Hermitte: It is a question of definition. We can separate the manufacturers who want to have particles in their fillers and the ones who want to make their fillers more malleable and supple. By design, there is a big difference between, for example, Emervel or Restylane and between the other, let’s say, monophasic fillers.
If the Emervel or Restylane ranges use different sized particles to treat the different layers of the skin, the manufacturers of monophasic fillers play on elasticity and cohesiveness. We cannot have cohesiveness with particulated products. But when you inject in the dermis, thanks to this cohesiveness you have something more supple, more malleable and more easy to place under the skin.
The homogenisation of terminology between all manufacturers is needed to clarify the messages
Q: Would you agree with Dr Williams that all HAs are particulate?
Dr Laurence Hermitte: When you take Emervel or Restylane, you can feel the particles in your hands. You won’t be able to feel any particles when you touch Belotero, Juvéderm or Jolidermis.
Dr Stefanie Williams: But small particles are still particles, depending on the product. Some of the microscopic Juvéderm images show quite large particles—they have to because they want to create volume.
I fully agree that it is a question of definition however and at the moment every company seems to come up with their own definition and an accompanying three-letter word of a technology that sounds quite good. However, the fact remains that they have to be particular because otherwise you can’t inject them.
If you feel a Sub-Q gel, you can actually feel the particles between your fingers (compared to, for example, Restylane Touch), as Sub-Q has a higher lifting capacity and a much higher resistance to deformation.
With regards to definitions, it’s the same problem with so-called monophasic and biphasic fillers. The NASHA products are actually not biphasic. A true biphasic product wouldn’t work as a filler, if you think of two separate phases.
What happens in the NASHA gel is that the the HA particles swell up with the surrounding water or saline and then sit so close to each other, that there is practically nothing inbetween. This is not what I would define as biphasic. There is only one phase, which is the swollen HA particles.
Q: But in Restylane, you have uncross-linked HA, which helps those particles go through the syringe. Is the uncross-linked HA in Restylane mixed in with the particles the lubricant to allow them to go through?
Dr Stefanie Williams: I’m not sure—as far as I was aware, there isn’t anything in between. The water or saline has absorbed into the particles, so they are all sitting next to each other.
Mr Peter Sharma: The cross-linked particles suspended in a gel which contains free, non-cross-linked hyaluronic acid. Monophasic and biphasic is misleading terminology.
Q: But we don’t have uniformly accepted chemical terms to describe these long-chain polymers. In literature, we have to talk about manufacturing technology because there is no uniform way of referencing the differences between molecules. We have specific ways to describe the molecular structure, but we don’t have that with these long-chain polymers.
Mr Peter Sharma: That’s true. But I would just say that the hydrogen particle technology used by Uma Jeunesse is a total departure from everything else. Now, this is a biphasic product which behaves like a monophasic in the traditional definition of these words. So I suggest that we move away from this monophasic, biphasic sort of thinking.
But there is free HA in Restylane. It is the carrier. You get initial transient swelling with Restylane or Perlane, which you don’t get with products like Juvéderm or other biphasic cross-linked gels. The reason for the swelling is the free HA that act as a lubricant. You get that initial transient swelling for 24–48 hours.
Dr Alain Lajeunie: From our practice, we think that Q-Med products are very hydrophobic and not hydrophilic, so I’m not sure that this sort of product produces a big swelling reaction. From orbital exploration—we inject a lot of orbits—we know that Q-Med products are quite safe concerning the hydrophilic and not so hydrophilic.
Q: If the increase in cross-linking of a product is linked to inflammation, do we see this clinically? Has a study been published anywhere?
Dr Chantal Belin: Preclinical studies have been done but no studies have been published. You probably see it clinically that the higher cross-linked product gives more side effects such as erythema.
Q: In a study comparing Revanesse to Restylane, Restylane showed a little more redness and more telangiectasias. Could you comment on this inflammatory reaction?
Dr Martyn King: The big difference seems to be in the technology of the cross linking. There does seem to be an optimum amount of cross linking—the more you cross link, the quicker it gets broken down.
Cross linking does help the stability and longevity but you hit a point and it seems to be inversely proportional. I suspect that that is down to the inflammation as well in the degradation of the product. I also think Restylane tends to be benchmarked a lot in these trials.
I’ve used Restylane quite a bit in my career and in terms of correction, there used to be a bit of overcorrection. If I tried to put it into science that this is to do with the non-cross-linked HA gel that you initially put in, which gets broken down within 24 hours. The other products have to be cut to get the gel through a needle.
But clinically, at the end of the day what we see is results. However they cut the gels and whatever they do to them, you do get a nice correction immediately after. Then you get them back within two weeks, two months and you still have that correction. So they are maintaining their integrity one way or another.
