From the age of thirty, hyaluronic acid, collagen and elastin in the dermis (dermis) decrease. As a result, the skin is increasingly less able to repair damage, for example caused by sunlight and skin diseases. A relatively new method to supplement these deficiencies consists of injectable biostimulators based on polynucleotides. Read here what polynucleotides are, how they work and how they can be used to improve the skin.
What are polynucleotides?
Polynucleotides are chains of nucleic acids that occur naturally in our bodies. A nucleic acid is a complex macromolecule consisting of a large number of linked nucleotides. The nucleotides adenine, cytosine, guanine and thymine form the building blocks of the nucleic acid and their sequence determines the genetic information. The best known and most common natural nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
Polymerized polynucleotides, also called polydeoxyribonucleotide (PDRN), are used in cosmetic medicine. To produce this PDRN, DNA fragments are extracted from the sperm cells of the Oncorhynchus mykiss (rainbow trout) or Oncorhynchus chain (chum salmon or keta salmon). Sperm cells are the most suitable source of polynucleotides because the DNA in them is very pure, without contamination by peptides, proteins or fats. This means that the chance of immunological reactions is as small as possible.1
How do polynucleotides work?
Polynucleotides are very important for cell division, cell repair, wound healing and tissue regeneration. Through these processes, polynucleotides have a positive effect on tissues and organs, including the skin. Their operation is based on the following mechanisms.
Binding to adenosine A2A receptors
Fibroblasts are cells in the subcutaneous connective tissue that have a number of essential functions. In this way they produce the components that together form the so-called extracellular matrix; the substance that occurs between cells. This intermediate cell substance consists of collagen, elastic and reticular fibers, glycosaminoglycans (including hyaluronic acid) and the glycoproteins of the basic substance (matrix). Collagen is a non-elastic fiber that provides the strength of the tissue. Reticular fibers – which connect connective tissue and other tissues – also provide strength, while elastic fibers (also called elastin) provide stretch and elasticity of tissue and organs. Thanks to the production of these substances, fibroblasts play an important role in the firmness and elasticity of the skin.3,4 Polynucleotides stimulate the production and growth of fibroblasts. Although the exact mechanism is not (yet) known, both in vitro and in vivo experiments suggest that polynucleotides stimulate the production of collagen by fibroblasts by binding to the adenosine A2A receptors.2-4 The production of substances such as collagen and elastin by fibroblasts contributes to better wound healing. But polynucleotides also promote wound healing in other ways. For example, binding of polynucleotides to the adenosine A2A receptors increases the production of vascular endothelial growth factor (VEGF). VEGF causes an increase in angiogenesis; the new formation of blood vessels. Angiogenesis leads to better blood circulation in tissues, which also improves wound healing.2,3 In addition to collagen and elastin, hyaluronic acid is also part of the extracellular matrix. An increase in fibroblasts therefore leads to more production of hyaluronic acid, which – in relation to its mass – can bind and retain very large amounts of water. In this way, the polynucleotides provide intensive hydration of the tissue.2
Stimulation of the salvage pathway
In addition, polynucleotides stimulate the so-called ‘salvage pathway’, an important part of nucleotide metabolism. During such a salvage pathway, purines and pyrimidines are formed from intermediate products that arise during the breakdown of the nucleic acids DNA and RNA. A salvage pathway can therefore be seen as recycling of nucleotides so that DNA can be repaired. This process is of great importance because some body tissues are not able to produce nucleotides themselves. This often applies, for example, to damaged and/or hypoxic tissue. In this way, polynucleotides help to accelerate wound healing and also to repair other damage, for example caused by the sun.2,3
Anti-inflammatory effect
Polynucleotides also have an anti-inflammatory effect subcutaneously. They act as a strong antioxidant and prevent oxidative damage by scavenging free radicals. Free radicals are highly reactive oxygen molecules that can damage cells, including in the skin.2,3
Application for skin improvement
Polynucleotides are among the skin’s own stimulating substances that encourage the skin to repair itself and remain beautiful for a longer period of time, also known as ‘skin boosters’. These substances have been increasingly used in recent years, both in medical and cosmetic medicine. For example, it has been known for some time that polynucleotides are effective in promoting wound healing in diabetic foot problems. They can also be used successfully for scars – for example from acne or after surgery – but also for (inflammatory) skin diseases, (sun) damage and hyperpigmentation.
Figure 1. Treatment with PDRN against melasma and an old scar on the upper lip, before treatment (A) and after (B)
During treatment with PDRN, the gel is injected into the area to be treated with a series of injections with a thin needle. After the treatment, the skin may be somewhat red and bumps may appear at the site of the injections, which will disappear within a few days. PDRN can be administered to any skin type and anywhere, such as the face (including the eyelids), the eyebrows, the neck, or on the hairy head. You start with 3 treatments in a row, with intervals of 2 to 4 weeks. To maintain the results of PDRN, maintenance treatment is performed once every 3-6 months. The substance is broken down by the body over time, causing the effects to gradually fade. How often repetition is necessary depends, among other things, on the condition of the skin, which areas are treated and the individual response to the treatment. Various studies are currently underway into further application of the technique in other conditions, such as autologous skin transplantation, thermal injury (frostbite or burns), osteoarthritis, plantar fasciitis (heel spur) and lichen sclerosus.2 The preliminary results are promising and it is expected that the drug can be used much more widely in the future.
What are the effects?
- Makes scars (including stretch marks), shallow wrinkles and other blemishes less visible
- The skin looks smoother and firmer
- More even skin tone (fewer dark circles around the eyes, discoloration and pigment spots)
- Better hydration
This article was partly based on the presentation during the EADV conference 2023 in Berlin by Drs. Petra Dikrama, dermatologist in the Erasmus MC te Rotterdam and with Dikrama Clinics in Utrecht
References:
2024-03-01 16:02:56
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