8th February 2023

The History and Evolution Of Hyaluronic Acid

Last Modified: February 9, 2023

Hyaluronic acid (officially known as hyaluronan) is one of the most significant medical discoveries of the last century. Its benefits for the body and skin are numerous, scientifically-backed, and far-reaching. Almost every year, a new development proves just how valuable hyaluronic acid is.

Here are some of the significant ones:

  • Promotes healthier, more supple skin by binding water to help retain moisture
  •  Speeds wound healing by regulating inflammation levels and signalling the body to form more blood vessels in the damaged area.
  •  Relieves joint pain by keeping the space between the bones lubricated.
  •  Reduces acid reflux symptoms by soothing the oesophagus's damaged lining and speeding the recovery process.
  •  Relieves dry eyes and discomfort by helping to moisten the eyes.

And research shows we are just scratching the surface of hyaluronic acid's role in the body. So it's no surprise that through human ingenuity, we have found a way to harness the power of hyaluronic acid in countless external applications. Some of the most popular are:

  • Hyaluronic Acid Fillers
  •  Dietary HA supplements
  •  Hyaluronic acid serums and gels
  •  Eye drops
  •  Hyaluronic acid injections

Expanding markets and new chemical modifications are leading to more and more hyaluronic acid products entering the market. Research shows that the global hyaluronic acid market is expected to reach USD 16.8 billion by 2030, expanding at a CAGR of 7.45%.

But how did we get here? How did a substance meant to lubricate our bodies find its way to our shelves and operating rooms?

20th Century: The Discovery and Evolution of Hyaluronic Acid

1880s

The first study regarding HA dates back to 1880: French scientist Pierre Portes observed that the mucin of the eye's vitreous body was different from the mucus found in the cornea and cartilages and named it "hyalomucine."

The 1930s

It was not until fifty-four years later that German biochemist Karl Meyer and his colleague John Palmer isolated a previously unknown chemical substance from the eyes of cows. Because it was clear and contained uronic acid, one of the two sugar molecules found in large quantities in the vitreous humour, they named it "hyaluronic acid (HA)." The first part of the word is derived from the Greek word "hyalos," which means transparent, glassy appearance.

The 1940s and 50s

The physicochemical properties of HA were studied in detail in the 1940s. But it was not until 1954 that Meyer and Bernard Weissmann elucidated the chemical structure of hyaluronic acid. They identified it as a straight-chain polymer consisting of two alternating sugars, D-glucuronic acid and N-acetyl-D-glucosamine. This was a significant breakthrough that set the stage for the exogenous production of hyaluronan.

The 1960s

An increasing understanding of the biological functions of hyaluronic acid led to growing interest in its production and development as a medical product. During this period, scientists figured out how to extract hyaluronic acid from animal tissues, particularly human umbilical cord tissue and rooster combs, which have high concentrations of hyaluronic acid. In particular, rooster combs contain the highest hyaluronic acid concentrations ever reported for animal tissue.

Although this was a significant advance, there were still some problems with this approach in purifying unwanted contaminants (e.g., microorganisms, proteins). This was the impetus for the first studies to produce HA by bacterial fermentation and chemical synthesis. Hyaluronan was found in the capsule of several microbial pathogens such as Pasteurella multocida and Streptococcus.

These microorganisms produced hyaluronan to encapsulate their cells and formed a perfect camouflage against their host's defence system. Because the bacteria continuously excrete HA, scientists could extract the product while leaving the microbes intact.

The 1970s

After decades of research on hyaluronan, the first pharmaceutical grade HA was produced in 1979 by Hungarian inventor Endre A. Balazs. He developed an efficient method for extracting and purifying hyaluronic acid from rooster combs and human umbilical cords. The first patent for high-purity hyaluronic acid was granted in the same year.

The 1980s & 90s

In 1980, using the techniques introduced by Balasz, one of the first hyaluronic acid products was introduced. Named Healon, it was a product used in cataract surgery and is still manufactured to date. This marked the beginning of the industrial production of hyaluronic acid from animal sources for medical applications.

These included the treatment of joints, wound healing, drug delivery systems, and cosmetics as a hydrating and antiaging material. During this time, hyaluronan production by bacterial fermentation evolved to a mature technology overtaking HA extraction from rooster combs.

21st Century: Hyaluronic Acid Dermal Fillers

Cosmetic companies have used HA as a moisturising ingredient in their formulations for the past 20 years. An excellent example of its use is topical formulations such as moisturising creams and serums. By the turn of the century, HA was already known for its hydration properties and ability to combat skin dryness and dullness, especially as the skin ages.

But dermal fillers are probably the most popular application of hyaluronic acid in non-invasive anti-ageing treatments.

Since 2003, HA has been widely used in dermal fillers, injected into or under the skin to restore lost volume and correct facial imperfections such as wrinkles.

In 2003, the US Food and Drug Administration (FDA) approved Restylane, a hyaluronic acid product, for wrinkle treatment. In the years that followed, other brands, such as Juvederm, followed. Although Restylane was not the first HA dermal filler, it was the first non-animal stabilised hyaluronic acid filler.

Before Restylane, the hyaluronic acid in fillers was of animal origin, mainly from rooster combs. However, with the growing demand for vegan beauty products, rooster combs were primarily replaced by synthetic and fermented bacteria ingredients.

Another significant advancement in HA dermal fillers over the years is the introduction of lidocaine. Before, none of the dermal fillers had an anaesthetic component, and patients had to endure the mild pain associated with the procedure.

Now, lidocaine is added to many dermal fillers during the manufacturing process, which helps to reduce discomfort for patients.

There are so many options today as hyaluronic acid fillers have become the fastest-growing non-invasive cosmetic treatment in the world.

More now than ever, it's crucial to find an experienced injector who can recommend a suitable dermal filler and inject it correctly to achieve the desired results.

The Future of Hyaluronic Acid

With its exceptional properties and numerous and varied applications, hyaluronan has proven to be an excellent material for medical, pharmaceutical, and cosmetic applications. Although it is already well established in its existing applications, HA still has growth ahead of it.

Stimulated by the development of new production techniques and the growing knowledge of the biological function of hyaluronan, research is being pursued to improve existing HA products and validate new concepts for medical and cosmetic therapies.

Post Reviewed by: Dr Baldeep Farmah
Medically Reviewed on: 8th February 2023
Dr Baldeep Farmah is the Medical Director and lead Doctor of Dr Aesthetica, a Medical Aesthetic Clinic.

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