Polynucleotides and the Regenerative Shift

Polynucleotides and the Regenerative Shift: What the 2026 Aesthetic Medicine Trend Means for Nonsurgical Phalloplasty

Luis Casavantes, MD and Palmira Morales, MD

Avanti Derma™, Tijuana, Mexico

Aesthetic medicine has spent much of the last two years moving away from a "more volume" mindset and toward a "better tissue" one. In facial aesthetics, this shift shows up as a swing away from heavy hyaluronic acid filling and toward polynucleotide (PN) and polydeoxyribonucleotide (PDRN) skin boosters — treatments designed to stimulate the tissue itself rather than simply occupy space within it. The same regenerative logic is increasingly being asked about by patients considering nonsurgical phalloplasty, and it is worth addressing directly, with the same evidence-first approach we bring to any new material or protocol.

What PDRN and polynucleotides actually are

PDRN is a purified DNA-fragment biopolymer, most often derived from salmon or trout milt, that has been used in wound care and tissue-repair medicine since the 1990s, well before it became a cosmetic ingredient. Its primary mechanism of action is activation of the adenosine A2A receptor, which in turn increases vascular endothelial growth factor (VEGF) expression, supports fibroblast activity and collagen synthesis, and modulates the inflammatory cascade that governs how tissue heals.¹ This is distinct from what a volumizing filler does. A PMMA or HA-based filler adds physical bulk; PDRN is intended to influence the biological environment the filler sits in — vascularity, collagen quality, and inflammatory tone.

Why patients are asking about it

Two things are converging. First, the broader aesthetics market has embraced polynucleotides as the "next step after PRP" for skin quality, and that framing is reaching patients who are separately researching genital aesthetic procedures.² Second, our own long-standing use of PRP as a regenerative adjunct to PMMA-based girth enhancement has already primed patients to think about tissue quality, not just volume, as part of the treatment plan.

What the evidence actually supports right now

It is important to be precise here, because this is where marketing claims tend to run ahead of data. The clinical evidence base for PDRN is genuinely strong in several domains — dermal wound healing, tendinopathy, periodontal regeneration, and general dermatologic tissue repair, where systematic reviews have documented improved healing, reduced inflammatory markers,  and increased angiogenesis.¹ ³ ⁴ What does not yet exist is a body of published, peer-reviewed evidence specific to penile soft tissue or to its use alongside PMMA in nonsurgical phalloplasty. The mechanism is biologically plausible and consistent with what we already understand about tissue integration around PMMA microspheres — which is the same reasoning that supported the earlier adoption of PRP as an adjunct, a rationale I laid out in more detail in my 2016 paper in the Journal of Sexual Medicine and again in Girth Matters (2022). But plausibility is not the same as proof, and I want patients to understand that distinction before any conversation about incorporating a newer regenerative agent into their treatment.

How we're approaching it at Avanti Derma

Our position is the same one we apply to every emerging material: adopt cautiously, disclose the actual state of the evidence, and never present an extrapolated mechanism as an established outcome. PRP earned its place in our protocols because both the rationale and a growing, procedure-relevant safety record supported it. Polynucleotides may eventually reach that same bar for genital tissue applications, and we are following the literature closely as more urologic and andrological data emerges. Until direct evidence exists, we discuss PDRN with patients as an area of active interest, not as a standard part of the girth-enhancement protocol.

This is, in the end, the same conversation I try to have in every consultation: the goal is not to be first to adopt whatever is trending, but to be clear with patients about what a treatment can actually be expected to do, based on what the data currently shows for that specific tissue and that specific application.

Bibliography

Bizzoca, Davide, Giovanni Brunetti, Lorenzo Moretti, Andrea Piazzolla, Giovanni Vicenti, Francesco Luca Moretti, Giuseppe Solarino, and Biagio Moretti. "Polydeoxyribonucleotide in the Treatment of Tendon Disorders, from Basic Science to Clinical Practice: A Systematic Review." International Journal of Molecular Sciences 24, no. 5 (2023): 4582. https://doi.org/10.3390/ijms24054582.

Mari, Ranjith, Jaiganesh Ramamurthy, K. Rudhra, and Nitya Krishnaswamy. "Efficacy of Polydeoxyribonucleic Acid (PDRN) in Periodontal Regeneration: A Systematic Review of Clinical Outcomes." Journal of Oral Biology and Craniofacial Research 15, no. 3 (2025): 624–30. https://doi.org/10.1016/j.jobcr.2025.03.021.

Marques Therapy. "PDRN & Polynucleotide Skin Boosters: The Regenerative Treatment London Is Turning to in 2026." Accessed July 20, 2026. https://www.marquestherapy.com/post/pdrn-polynucleotide-skin-boosters-the-regenerative-treatment-london-is-turning-to-in-2026.

Oh, Nuri, Juyoung Hwang, Moon Sung Kang, Chung-Yul Yoo, Minseok Kwak, and Dong-Wook Han. "Versatile and Marvelous Potentials of Polydeoxyribonucleotide for Tissue Engineering and Regeneration." Biomaterials Research 29 (2025). https://doi.org/10.34133/bmr.0183.