Use of Polydeoxyribonucleotide (PDRN) in Cosmetic Products: Biological Mechanisms of Action and Current Approaches

Polydeoxyribonucleotide (PDRN) is a biologically active nucleotide polymer, obtained particularly from the sperm DNA of salmonid fish, that supports tissue repair and cellular regeneration. First used in wound healing and regenerative medicine applications, PDRN has in recent years also begun to attract interest in the field of aesthetic dermatology and cosmetics. The biological effects of PDRN are mainly explained by the activation of adenosine A₂A receptors and the support of the nucleotide salvage pathway. Through these mechanisms, fibroblast proliferation, collagen synthesis, angiogenesis and tissue regeneration are stimulated while the inflammatory response is suppressed. Experimental and clinical studies show that PDRN can increase skin elasticity, accelerate wound healing, and support the healing process following aesthetic procedures. However, the majority of existing clinical evidence is based on PDRN preparations administered via injection. Its efficacy in topical cosmetic products is still being investigated, depending on its capacity to penetrate the skin barrier and on formulation characteristics. In this review, the biological mechanisms of action of PDRN, its areas of use in cosmetic products and its future application potential are summarized in line with current literature.

In recent years, cosmetic science has moved away from classical approaches aiming only to improve the appearance of the skin and has turned toward active ingredients capable of regulating biological processes at the cellular level. In line with these developments, many biomolecules used in the field of regenerative medicine have also begun to be evaluated in the development of cosmetic products. Polydeoxyribonucleotide (PDRN), one of these biomolecules, is one of the biological agents attracting attention in aesthetic dermatology and cosmetic applications due to its tissue regeneration-supporting effects. PDRN is a high-purity biopolymer generally obtained from the sperm DNA of salmonid species such as salmon (Oncorhynchus mykiss) or chum salmon (Oncorhynchus keta), consisting of deoxyribonucleotide chains of varying lengths. Thanks to its safe production processes and low immunogenic properties, it has been used in clinical applications for many years. 

The biological effects of PDRN are explained by two main mechanisms. The first is the suppression of inflammation and the increase in vascular endothelial growth factor (VEGF) synthesis as a result of the activation of adenosine A₂A receptors. This effect supports new blood vessel formation (angiogenesis), facilitating the transport of oxygen and nutrients to damaged tissues. The second mechanism is the reuse by cells of the nucleotides formed by the breakdown of PDRN. This process, referred to as the salvage pathway, accelerates cell proliferation, particularly by providing the building blocks required for DNA synthesis in rapidly proliferating fibroblasts and keratinocytes. The joint operation of these two mechanisms forms the basis of wound healing and tissue regeneration. 

Skin aging is a complex process that develops as a result of environmental factors such as ultraviolet (UV) rays, air pollution, oxidative stress and chronic inflammation, in addition to genetic factors. In aging skin, the number of fibroblasts decreases, the organization of collagen and elastin fibers deteriorates, and the activity of matrix metalloproteinases increases. These changes result in wrinkle formation, loss of elasticity and delayed wound healing. Studies show that PDRN increases fibroblast proliferation, supports Type I collagen synthesis, reduces inflammation and contributes to the reorganization of the dermal matrix. For this reason, PDRN is regarded as a promising active ingredient in anti-aging cosmetic products. 

The cosmetic applications of PDRN are not limited to anti-aging products alone. It is also used to accelerate the healing of controlled tissue damage occurring after aesthetic procedures such as fractional laser, chemical peeling and microneedling. Clinical studies report that PDRN applications can reduce post-procedure erythema and edema, accelerate the re-epithelialization process, and increase patient satisfaction. In addition, positive results have also been reported in dermatological problems such as acne scars, chronic wounds and postinflammatory hyperpigmentation. 

In recent years, there has been a notable increase in the number of topical cosmetic products containing PDRN, such as serums, creams and ampoules. However, unlike PDRN preparations administered via injection, scientific data on whether the molecule can sufficiently cross the stratum corneum barrier in topical products are still limited. For this reason, new carrier technologies such as liposomes, nanoemulsions, hydrogels and microneedle systems are being developed with the aim of increasing the bioavailability of PDRN. Although topical PDRN products currently appear promising, more randomized controlled clinical studies are needed to confirm their efficacy.

Polydeoxyribonucleotide stands out as one of the innovative active ingredients carried over from the field of regenerative medicine to cosmetic science, thanks to its biological properties supporting tissue regeneration. Through its effects exerted via the activation of adenosine A₂A receptors and the salvage pathway, it increases fibroblast activity, supports collagen synthesis, reduces inflammation and accelerates wound healing. Due to these properties, it has significant potential in anti-aging products, post-aesthetic-procedure care applications, and cosmetic formulations targeting skin regeneration. 

Nevertheless, when the existing scientific evidence is evaluated, it is seen that the strongest data on the efficacy of PDRN belong to preparations administered via injection. In topical cosmetic products, the capacity to overcome the skin barrier, the carrier systems used, and the formulation characteristics directly affect efficacy. For this reason, larger-sample and longer-term studies are needed to demonstrate the clinical efficacy of topical cosmetic products containing PDRN. In addition, the standardization of production processes, quality control, and the establishment of regulatory criteria will support the more reliable and widespread use of PDRN in the cosmetics sector. Current data show that PDRN may be an important biological active ingredient in the development of scientifically based cosmeceutical products in the future.