Learning about PDRN

Polydeoxyribonucleotides (PDRN), highly purified DNA-derived polymers, were approved by the Italian Medicines Agency (AIFA) in 1994 to treat superficial wounds, skin ulcers, and dystrophic connective tissue disorders. Since then, PDRN have gained considerable attention as regenerative biomaterials. Beyond their established role in wound healing, they have also been approved as dermal fillers in several countries, with growing clinical evidence supporting their benefits for facial skin health. Recent clinical and preclinical studies suggest that PDRN may improve various skin conditions, including wrinkles, dryness, hyperpigmentation, hair loss, and barrier dysfunction.

Although initially developed for the treatment of wound healing in dystrophic and ulcerative conditions, PDRN has recently been repurposed and approved in several countries as a medical device, particularly as a dermal filler. Because of its regenerative potential, PDRN is increasingly recognised as a bioremodeling filler, providing volumisation as well as functional improvement of the skin. This paradigm shift has broadened its application in aesthetic dermatology, addressing the limitations associated with traditional fillers.

Hyaluronic acid (HA)-based fillers are the standard treatment for wrinkle correction and facial volume enhancement. However, their role remains largely mechanical because HA lacks intrinsic bioactivity. Moreover, the high crosslinking densities necessary for structural durability are associated with an increased risk of adverse events. Synthetic crosslinkers such as 4-butanediol ether (BDDE) and polyethylene glycol diglycidyl ether (PEGDE), which are commonly used in HA fillers, have shown cytotoxicity, oxidative stress induction, and upregulation of pro-inflammatory cytokines at concentrations as low as 100 ppm.

Clinical reports have also associated HA fillers containing synthetic crosslinkers with complications such as hypersensitivity reactions, vascular occlusion, nodules, and granulomas. These challenges have prompted growing interest in biologically active fillers that promote tissue regeneration and volume restoration. PDRN-based fillers provide mechanical support as well as activate adenosine receptors, which mediate anti-inflammatory effects and tissue repair. In some regions, these agents are classified as skin boosters owing to their regenerative profile

PDRN-based fillers tend to exhibit a delayed onset of action, with visible improvements typically emerging after several weeks. To address this limitation, recent studies have explored hybrid formulations combining PDRN (PN in the original report) with other filler agents such as HA, aiming to harness the immediate volumising effect of HA alongside the long-term regenerative activity of PDRN. For example, Kim et al. (2020) demonstrated that HA-PDRN (PN in the original report) composites exhibit higher viscosity, elasticity, and in vivo durability than HA alone, while also promoting fibroblast proliferation and tissue regeneration.

Furthermore, Oh et al. (2021) reported that hybrid fillers composed of HA, PDRN (PN in the original report), and poly-L-lactic acid (PLLA) enhanced cell migration and collagen synthesis, while reducing pain and irritation, effectively overcoming certain drawbacks of PN-only formulations. A more recent clinical study (2025) confirmed the efficacy of HA-PDRN (PN in the original report) hybrid fillers. Using a multiple micro-aliquot injection technique, investigators observed significant improvements in periorbital wrinkles, skin texture, and brightness, along with faster clinical onset and shorter downtime. Although these findings present promising strategies to overcome the inherent limitations of PDRN-only formulations, further well-controlled clinical trials comparing hybrid formulations with monocomponent fillers are warranted.

PDRN exerts a range of regenerative effects in dermatology, including enhanced skin texture, wrinkle reduction, and accelerated wound healing. Although its current regulatory approval is limited to use as wound healing agents and dermal fillers, numerous preclinical studies have highlighted its broader dermatological potential. Specifically, PDRN has been shown to enhance skin cell proliferation, stimulate collagen and elastin fiber synthesis, and reduce inflammation and hyperpigmentation.

PDRN-based agents, initially developed for wound healing, are now used globally as regenerative therapies and dermal fillers. As clinical and preclinical evidence grows for their benefits in skin health, interest is increasing in repositioning these agents for conditions such as psoriasis, alopecia, melasma, atopic dermatitis, and rosacea. Understanding alternative mechanisms—particularly those involving exDNA—may further broaden PDRN’s therapeutic potential and clinical applications in dermatology.

PDRN-based dermal fillers have been widely adopted across global markets, including Asia, with accumulating clinical data confirming their safety and efficacy profiles for skin rejuvenation. Unlike HA fillers, which offer predominantly mechanical effects, PDRN-based fillers provide biostimulatory activity, promoting endogenous tissue repair and regeneration. These advantages support the development of combination strategies, incorporating HA or adjunctive modalities such as microneedling, ultrasound, or laser therapy, to further enhance clinical outcomes in aesthetic dermatology

A significant body of evidence supports their safety, with adverse effects limited primarily to minor symptoms such as transient pruritus at the injection site. Numerous in vitro, in vivo, and clinical studies have consistently revealed their efficacy in enhancing skin hydration, improving wrinkles, promoting hair growth, modulating pigmentation, and stimulating cellular proliferation, indicating strong potential for broader dermatological applications.

(Polydeoxyribonucleotides (PDRN) are natural DNA-derived polymers, typically sourced from salmon or trout sperm, known for tissue regeneration, wound healing, and anti-aging properties = Italics, here, are mine.)

NOT MY OWN WORK. Taken from (and for more information), see:

Park, S.; Baek, S.; Shin, H.-J.; Kim, J.-S.; Gwon, H.-I.; Bae, S.; An, S. Polydeoxyribonucleotides as Emerging Therapeutics for Skin Diseases: Clinical Applications, Pharmacological Effects, Molecular Mechanisms, and Potential Modes of Action. Appl. Sci. 2025, 15, 10437. https://doi.org/10.3390/app151910437

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