Biochemical properties of hyaluronic acid in biorevitalizants

Yulia Kievskaya, Candidate of Biological Sciences, scientific director of YK School, cosmetologist-pharmacist

The beautiful and attractive phrase “Biorevitalization is the gold standard of cosmetology” has a serious scientific basis. Just look at the following theses:

• over 40 years of studying this biopolymer from 1966 to 2006, 14,000 scientific publications were published;
• 30-50 patents are associated with the production and further use of HA annually;
• Since 1985, regular conferences dedicated to hyaluronan have been held;
• In 2004, the International Society for the Study of Hyaluronic Acid (ISHAS) was created.

And now there is an active study of this simple and at the same time multifaceted biopolymer.

In the previous article, we examined more general parameters for selecting a drug for biorevitalization . This time we will focus on the biochemical parameters of hyaluronic acid or, more correctly, hyaluronan, which is the main active ingredient in biorevitalizant.

Basic biochemical quality criteria for HA

When choosing a drug for biorevitalization, a specialist should pay maximum attention to three key aspects :

1. molecular weight (i.e. the size of the molecule);
2. concentration in the finished product;
3. form - native (natural) or modified (using cross-links).

Molecular mass

Speaking about biological activity, it is necessary to highlight a feature of HA, namely the dependence of the processes on the molecular weight of the macromolecule.

Various-sized fragments of HA serve as signals for cells and control processes such as:

• inflammation;
• tissue repair;
• cellular differentiation;
• morphogenesis;
• angiogenesis.

The cellular response to these signals depends on the cell type and size of the GC. By binding to their receptors, fragments of polysaccharide molecules trigger cascades of reactions.

There is some discrepancy in the interpretation of sizes in scientific publications, namely the division depending on the number of disaccharide residues.

HMHA (high molecular weight hyaluronic acid) from 1 million Da

• maintains optimal matrix properties;
• prevents excessive cell proliferation;
• limits inflammation and immune reactions;
• has pronounced antioxidant activity, neutralizes free radicals and suppresses lipid peroxidation processes.

LMHA (low molecular weight hyaluronic acid) less than 1 million Da up to 10 kDa

• weakens apoptosis, enhances cell differentiation;
• stimulates the expression of proinflammatory cytokines, chemokines and growth factors;
• may induce angiogenesis and tumor progression.

Let's look at a few examples closer to practice. Thus, the introduction of low-molecular HA drugs with pro-inflammatory properties during a hyperactive or prolonged post-peeling period can slow down the patient’s rehabilitation. High molecular weight HA should not be chosen for patients with any inflammatory dermatopathology in the acute stage, since suppression of the activity of the local immune response can become a serious obstacle to the resolution of inflammation.

It should be borne in mind that any polysaccharide is not homogeneous. All hyaluronan samples are a mixture of macromolecules of different lengths, that is, one sample can contain molecules of different lengths. That's why they talk about the average value. Unfortunately, the presence of low molecular weight fractions of HA can have undesirable side effects on the body when injected with drugs.

Concentration

Frequently asked question: will a higher concentration and volume of the drug give better results?

A small calculation will answer our questions:

Injection area area 20*20 cm = 400 cm2

Dermis thickness 4 mm

Volume = 160 cm3

Physiological concentration in the dermis 0.5 mg/ml

The physiological amount of HA is 160 cm3*0.5 mg/cm3 = 80 mg.

We know that until a certain age the amount of hyaluronic acid does not change, but there is a seasonal fluctuation of up to 15-20%

The maximum biorevitalizing effect can be achieved by introducing:

• 2-2.5 ml 0.5% HA;
• 1-1.5 ml 1% HA.

What happens if a larger amount and concentration of the drug is administered in one procedure?

• Studies show that exceeding the concentration by 1% leads to a dose-dependent decrease in fibroblast survival.
• At a concentration of 2%, there is a 20-25% drop in the metabolic activity of fibroblasts.
• A decrease in metabolic activity can lead to a mismatch between the processes of catabolism and anabolism.

In addition, when administering highly concentrated GC preparations:

• a sparingly soluble three-dimensional gel structure is formed;
• when such a hydrogel enters the dermis (aquatic environment), they begin to draw water from the intercellular space;
• moisture content may decrease in the first 2 weeks, and only by the end of the 4th week does moisture content increase;
• when significant amounts of GC are administered, a stress factor arises;
• pH and ionic composition change, the structure of matrix proteins is disrupted, hydrophobic amino acids - tryptophan, tyrosine, finylalanine - appear on the surface of protein aggregates. They actively absorb UV radiation of 280-320 nm with the formation of amyloids and free radical processes.

One of the indicators of overdose may be papules that do not resolve for a long time (a day or more).

It is worth understanding that a one-time excess of the dose will not have serious consequences, but a course (3-5 procedures) with a frequency of 2-3 times a year can worsen the skin condition.

Native & modified HA

The use of cross-linked and non-cross-linked hyaluronic acid has its own advantages and indications.

Native is hyaluronic acid without foreign cross-linking agents and ballast substances. The absence of foreign compounds in the preparation is a condition for rapid reproduction of the physiological effects of native hyaluronic acid. Cell receptors recognize the native molecule, and lidase enzymes “cut” the “correct” fragments with a certain chain length and the required biological activity:

• recreation of the physiological environment;
• prolonged stimulating effect on the microenvironment;
• reproduction of the biological effects of a natural analogue;
• restoration of turgor of the adaptive resource;
• stimulation of the production of own HA.

To “hide” hyaluronic acid and protect it from rapid degradation, its chains are cross-linked with each other through chemical bonds, forming a polymer network. Today, there are drugs on the market that are a mixture of HA in two fractions - stabilized (cross-linked) and unstabilized (native). Such preparations, on the one hand, act as a dermal filler due to slowly degrading stabilized HA, and on the other hand, as a biorevitalizant due to native HA, which quickly undergoes splitting into fragments with all the ensuing biological consequences.