Why Everyone Is Talking About Polynucleotides
Over the last few years, polynucleotides have moved from niche conference slides into mainstream aesthetic conversations. You see them in skin boosters, fillers, “biostimulatory” treatments, and now even topical strategies for aging skin.
At their core, polynucleotides (PN) are chains of nucleotides, the same basic building blocks that make up DNA and RNA. In laboratory and clinical settings, they have been studied for their ability to support cell proliferation, tissue repair, and overall skin quality. In aesthetic medicine, that has translated into interest around texture, wrinkles, and visible signs of aging.
The review you are reading from here looked across the current PN and PDRN literature in aesthetic settings and did something important. It separated what is documented from what is still theory, and it graded the strength of the evidence instead of treating every study as equal.
That is the level of honesty we align with at DERMA-CODE.
PN and PDRN: Related, Not Identical
In everyday conversation, “polynucleotides” and “PDRN” are often used interchangeably. The review makes it clear they are related but distinct.
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PDRN (Polydeoxyribonucleotide)
PDRN is a mixture of DNA fragments typically derived from salmon sperm. These fragments supply nucleotides that support repair processes and have been studied for their role in cell proliferation, angiogenesis, and anti inflammatory activity.
- PN (Polynucleotides) as a broader category
The paper notes that PN used in injectables and scaffolds are usually derived from testes rather than sperm, have longer chains, higher molecular weight, and a three dimensional scaffold structure that is different from PDRN. That structure may influence how they interact with the extracellular matrix.
In practice, much of the mechanistic language used to describe PN is borrowed from PDRN data. The authors are very clear that for PN themselves, the exact mechanism has not yet been fully demonstrated. Mechanisms are inferred because the molecules are similar, not because PN have been mapped in the same depth as PDRN.
That nuance matters if we care about scientific honesty.
How PDRN Appears To Work
The review describes two main pathways through which PDRN is thought to act.
1. A2A receptor pathway: PDRN can stimulate adenosine A2A receptors, which triggers a cascade that increases cyclic AMP, activates protein kinase A, and influences transcription factors such as NFκB, CREB, and HIF-1. This chain links to vascular growth factors like VEGF and angiopoietin, which are involved in angiogenesis and tissue recovery. In simple terms, it helps create a more supportive environment for repair, especially in stressed or oxygen deprived tissue.
2. Salvage pathway: PDRN fragments can be broken down into nucleotides that are reused in DNA synthesis. This “recycling” is part of how cells maintain a sufficient pool of building blocks for replication and repair.
Across the studies reviewed, higher local DNA content seems to correlate with more active tissue regeneration, particularly in challenging or damaged environments.
Preclinical work has also shown PDRN:
- Supporting repair of UV induced DNA lesions in fibroblasts
- Influencing melanogenesis pathways
- Affecting mitochondrial biogenesis and metabolic activity
These findings sit upstream of cosmetic outcomes. They describe what may be happening at the cell level, not guaranteed visible results in every patient.
Where Polynucleotides Are Being Used Today
The review groups current PN and PDRN use into several aesthetic categories. Most of these involve injectables or device assisted treatments in medical settings, not over the counter skincare.
1. General skin quality and “skin boosters”
Multiple papers describe PN based skin boosters that are injected into the dermis to improve:
- Skin texture
- Elasticity
- Hydration
- Fine lines and overall radiance
Some reviews and trials report improved elasticity and wrinkle depth, while others show more modest change. Evidence levels range from expert opinion and case series to a few randomized controlled trials. The trend is positive, but not every study is high level.
PN also appears as a delivery system in cosmeceutical research. Non woven PN based tissues have been studied as carriers that can:
- Stabilize active ingredients
- Improve skin penetration and bioavailability
- Provide controlled release
- Reduce local irritation compared to certain direct applications
That line of work is closer to how topical skincare operates.
2. Wrinkles and biostimulatory fillers
Several clinical studies, including randomized controlled trials, compare PN fillers to more familiar options such as hyaluronic acid and polycaprolactone in areas like crow’s feet and lateral canthal lines.
Across these studies, PN based products generally:
- Improve wrinkle depth and texture
- Support elasticity and hydration
- Show similar or better durability compared to some comparators
- Are well tolerated, with minimal adverse reactions reported
Again, most of these are injectable therapies performed by physicians, which sit outside cosmetic skincare. They are part of the broader story of how this class of molecules behaves in living tissue.
3. Erythema, scars, and stretch marks
The review also covers PN in:
- Acne scars
- Post surgical scar prevention
- Facial erythema
- Stretch marks
Several small studies and case series report improvements in scar quality, texture, and patient satisfaction when PN is part of the treatment protocol, often combined with other modalities like hyaluronic acid or growth factor approaches.
These are encouraging signals, but the authors note the limitations clearly. Many studies have small sample sizes, variable protocols, and short follow up.
4. Other areas and device combinations
There are early data on PN combined with:
- Microneedle radiofrequency for periorbital wrinkles
- Microneedle radiofrequency for melasma
- Specialized applications such as infraorbital dark circles
In most of these, adding PN appears to enhance the effect of the energy based device compared to the device alone, particularly for elasticity and texture. Once again, these protocols sit in procedural medicine rather than home skincare.
What The Review Says About Safety
One consistent theme across the aesthetic PN and PDRN literature is safety.
Across the studies reviewed:
- No serious adverse events were reported
- Most side effects were mild and transient, such as temporary redness or swelling at injection sites
- Products are described as highly biocompatible, often derived from salmon sources that have been purified and processed for medical use
The authors still call for longer term follow up, but the available data suggest a favorable safety profile when these materials are used appropriately.
PN As Scaffold: A Different Kind Of Support
One of the more interesting sections of the review looks beyond chemistry and into structure.
Scanning electron microscopy shows PN forming interconnected pentagon and hexagon shaped “cells” that create a three dimensional scaffold. These structures are smaller than a typical fibroblast and may offer a dense network for cells to attach to.
The authors connect this to age related changes in the extracellular matrix. As collagen becomes fragmented with age, fibroblasts have fewer anchoring points, lose mechanical stimulation, and reduce their collagen production. A PN scaffold in that environment could, in theory, provide new attachment sites and help restore some of that mechanical communication.
This is not yet proven in large human trials, but it is a useful way to think about polynucleotides. They are not only chemical messengers. They may also behave as physical architecture around cells.
Where The Evidence Is Strong, And Where It Is Not
The review is careful to grade evidence levels. Most of the PN literature in aesthetics today falls into:
- Level I and II for a limited number of randomized controlled trials on specific fillers or protocols
- Level III and IV for many case series and small cohort studies
- Level V for expert opinion pieces and mechanistic overviews
There is also considerable variability in:
- Dosing
- Injection patterns and depths
- Combination therapies
- Outcome measures and follow up periods
In plain language, the signal is promising, especially around skin quality, wrinkles, and texture, but the field still relies on many small or heterogeneous studies. Large, well controlled trials are still needed, and the optimal protocols are not yet standardized.
The authors repeat this point more than once. Polynucleotides are interesting and often helpful in the right hands, but they are not a solved equation.
How DERMA-CODE Interprets This Research
DERMA-CODE does not perform injectable procedures. Our work sits on the cosmetic side, with topical formulations based on PDRN, NAD⁺, and targeted peptides.
Here is how we read this review through that lens:
- It reinforces that PDRN is a well studied member of the PN family, with documented roles in supporting repair, angiogenesis, and response to UV related damage in experimental settings.
- It confirms that biocompatibility and safety are strong across a wide range of PN and PDRN uses when properly purified and handled.
- It highlights that mechanisms for PN products are often inferred from PDRN, and that the field as a whole still needs more high quality clinical data.
- It supports the idea that skin quality changes are more realistic and more honest to talk about than dramatic, isolated claims.
Our formulations are built for daily, cosmetic use, not for medical treatment of scars, melasma, or surgical outcomes. We use PDRN and supporting actives to create a favorable surface environment for comfort, balance, and visible texture, while respecting both biology and regulatory boundaries.
We also choose to be upfront about what is known and what is still developing. That is why we link directly to the literature instead of speaking in slogans.
Source And Further Reading
This article is based entirely on the following peer reviewed review:
Polynucleotides in Aesthetic Medicine: A Review of Current Practices and Perceived Effectiveness
Lee KWA, Chan KWL, Lee A, et al.
Available via PubMed Central:
https://pmc.ncbi.nlm.nih.gov/articles/PMC11311621/
We earn trust through results, not promises.
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