The birth of PDRN: from hospital wards to beauty clinics

A discovery born from desperation

Picture a hospital ward in Northern Italy in the early 1990s: long corridors, high ceilings, natural light streaming through tall windows. Doctors make their rounds, pausing at bedsides where stubborn wounds and ischemic ulcers refuse to heal — the difficult cases, where tissue damage resists even the best dressings and antibiotics. Week after week, the wounds remain open, putting patients at risk of infection, amputation, and worse.

The statistics were sobering. Research published in Diabetes Care would later show that approximately 15% of patients with diabetic foot ulcers would face amputation within five years. For elderly patients with peripheral artery disease, chronic leg ulcers meant not just pain but loss of mobility and independence.

In this challenging environment at institutions like the University of Milan and medical centers in Turin, pioneering teams began experimenting with an unconventional approach: biological extracts rich in DNA. Perhaps something in the fundamental building blocks of life could unlock the body's healing capacity.

What they observed was remarkable. Tissue that had been stagnant for months started to heal faster. Blood flow to damaged areas visibly improved. These findings would later be documented in Wound Repair and Regeneration — wound surface area decreased measurably, granulation tissue appeared more robust, and time to closure shortened significantly. Patients facing amputation were keeping their limbs.

The hunt for the active ingredient

The early successes sparked intense curiosity. What was driving this effect? The crude extracts contained proteins, lipids, nucleic acids, and numerous other components. Researchers systematically isolated and tested each fraction. Through years of methodical work, a pattern emerged: the therapeutic power resided in the DNA molecules themselves — specifically, fragments of DNA in particular size ranges.

The Goldilocks zone

Further research revealed something crucial: not just any DNA worked optimally. Whole DNA molecules were too large. Individual nucleotides were too small. The sweet spot was DNA fragments of approximately 50 to 1,500 base pairs — large enough to trigger cellular responses, small enough for practical production. This discovery, published in Frontiers in Pharmacology by Squadrito and colleagues, would become foundational to all PDRN development.

Think of it as communication: sending cells an entire encyclopedia (whole DNA) is overwhelming. Sending single letters (nucleotides) lacks information. But sending coherent paragraphs (DNA fragments) gives actionable information cells can use. This insight meant the active principle was a defined class of molecules that could be purified, standardized, and produced consistently: polydeoxyribonucleotide, or PDRN.

From placenta to fish: the source evolution

Knowing what worked and producing it reliably were different challenges. Researchers needed a DNA source that was abundant, pure, consistent, ethical, and economical.

Initial attempts used human placental tissue — it made sense, placenta is rich in nucleic acids and routinely collected after childbirth. But this source presented insurmountable problems: supply inconsistency as availability fluctuated with birth rates, ethical complexity requiring rigorous consent procedures, significant batch-to-batch variability from different mothers, inherent pathogen transmission risk, and regulatory hurdles that added years and costs to development.

The breakthrough came when researchers turned to fish milt — the sperm-containing fluid from cold-water fish like salmon and trout. This pivot was brilliant: sperm cells are nature's DNA delivery vehicles, and fish produce them abundantly. Studies published in the Iranian Journal of Fisheries Sciences demonstrated that fish milt contains up to 10% DNA by weight — extraordinarily high compared to typical tissues at 0.1–1%.

A single large salmon produces 200–400 grams of milt. Commercial fisheries handle thousands of fish daily, generating kilograms of milt, mostly discarded as waste. Using milt for PDRN created value from waste, aligning with circular economy principles and adding fishing industry revenue. Farmed and wild fish alike produced consistent DNA quality, as documented in vascular surgery research by Bitto and colleagues, and cold-water fish live in pristine environments with low pathogen loads — a favorable safety profile, since fish pathogens generally can't infect humans.

Most importantly, DNA is DNA. Watson and Crick's 1953 discovery of the DNA double helix revealed that the structure and four nucleotide bases are virtually identical across vertebrates. Human cells read and respond to fish DNA fragments just as they would human DNA — it's a universal molecular language.

Creating medical-grade PDRN

Through the late 1990s and early 2000s, pharmaceutical companies refined sophisticated processes to transform raw fish milt into standardized medical products. Fresh milt is first homogenized into a uniform mixture. Specialized enzymes then break down cell membranes and release the DNA while carefully preserving its structural integrity — too aggressive, and the DNA becomes damaged; too gentle, and yields are too low.

Once liberated from the cells, the DNA undergoes multiple purification steps to remove everything that isn't DNA — proteins, lipids, RNA, and cellular debris — through precipitation, filtration, and chromatography, often exceeding 95% purity. The purified DNA then enters the fragmentation stage, where controlled enzymatic digestion carefully cuts the long DNA molecules into the optimal therapeutic size range of 50 to 1,500 base pairs.

Before use, each batch is analyzed for molecular weight distribution, tested for sterility, checked for endotoxins, and verified for purity. Only batches meeting pharmaceutical-grade specifications proceed to final formulation — injectable solutions or topical preparations — producing, as detailed in International Wound Journal publications by Rubegni and colleagues, a consistent, sterile, pharmaceutical-grade product with reproducible composition and predictable therapeutic effects.

Clinical validation: PDRN proves itself

With standardized PDRN, clinical research accelerated. Research published in International Wound Journal by Valdatta demonstrated that diabetic ulcers and pressure sores treated with PDRN closed 30–40% faster than standard care alone, with better tissue quality and lower amputation rates — confirmed in Archives of Plastic Surgery studies by Kim and colleagues examining peripheral tissue oxygenation in diabetic foot ulcers.

For ischemic conditions, PDRN promoted new blood vessel formation. Research in Cardiovascular & Hematological Agents in Medicinal Chemistry by Altavilla showed enhanced tissue perfusion and symptom relief through therapeutic angiogenesis. Surgeons incorporated PDRN into complex reconstructions, seeing reduced healing time, as documented by Park in Archives of Plastic Surgery research on fat graft resorption reduction.

By the mid-2000s, PDRN had earned regulatory approval in numerous countries for therapeutic use, establishing itself as a valuable regeneration helper in wound care and vascular medicine — long before anyone considered it for beauty.

The aesthetic turn: from hospital to beauty clinic

As aesthetic medicine evolved — especially in South Korea, which emerged as a cosmetic innovation hub — forward-thinking practitioners began asking: if PDRN helps severely damaged tissue repair, what could it do for photo-damaged or aging skin?

Korean dermatologists pioneered «skin booster» protocols, injecting PDRN to improve overall skin quality. A multicenter, randomized, double-blind, placebo-controlled trial published in Dermatologic Surgery by Kim demonstrated thicker, more resilient skin, improved texture, and reduced fine lines. By the 2010s, PDRN had transformed from hospital wound treatment to sought-after beauty ingredient — the «salmon DNA» narrative dominated: pristine rivers, leaping fish, pure northern waters.

One ocean, many stories: beyond salmon

Here's where the story becomes more interesting. The salmon narrative, while beautiful and true, obscures an important reality: PDRN's activity doesn't depend on coming from salmon. DNA structure is universal across vertebrates. Research in Photodermatology, Photoimmunology & Photomedicine by Belletti showed that skin cells don't read a «species passport» — they respond to fragment size, purity, and concentration.

This opens possibilities beyond salmon. In the North Atlantic, Atlantic cod produces milt equally rich in DNA. Cod fisheries in Norway, Iceland, and northern Europe are among the world's most sustainable and carefully managed. Cod-derived PDRN speaks the same molecular language as salmon PDRN — same biological activity, different regional story: regional authenticity aligned with local marine industries, sustainability narratives connected to well-managed traceable fisheries, and economic integration supporting existing fishing communities.

It's not about replacing salmon — it's about expanding beyond a single-species narrative to recognize that PDRN's power lies in the universal language of DNA, not in one particular fish.

The broader value chain: beyond beauty

PDRN isn't the only valuable product from fish milt. When DNA fragments are broken down further, they yield nucleotides already used in animal feeds, aquaculture diets, and nutritional supplements. A well-designed biorefinery can fractionate fish milt into multiple streams: high-purity PDRN for cosmetics and regenerative medicine, nucleotide fractions for animal feed and supplements, proteins and peptides for additional applications, and lipids for omega-3 concentrates — minimal waste, maximum value.

A story still unfolding

The PDRN journey — from Italian hospital wards treating stubborn ulcers, through salmon-based medical products, into Korean aesthetic clinics, and now expanding to include cod and other marine sources — demonstrates how scientific innovation evolves. The science remains constant: DNA fragments in specific ranges activate regenerative pathways and improve tissue healing. But the story is becoming richer, more diverse, and more connected to broader conversations about marine resources, circular economy, and regional biotechnology.

The PDRN story isn't ending with salmon — it's just beginning to show its full potential.

Key references

• Squadrito, F., Bitto, A., Irrera, N., Pizzino, G., Pallio, G., Minutoli, L., & Altavilla, D. (2017). Pharmacological Activity and Clinical Use of PDRN. Frontiers in Pharmacology, 8:224.
• Galeano, M., et al. (2008). Polydeoxyribonucleotide in the treatment of diabetic foot ulcers. Wound Repair and Regeneration, 16(2), 208–217.
• Sheikhzadeh, N., et al. (2012). DNA extraction and quantification from fish tissues. Iranian Journal of Fisheries Sciences, 11(3), 677–686.
• Bitto, A., et al. (2008). PDRN restores blood flow in an experimental model of peripheral artery occlusive disease. Journal of Vascular Surgery, 48(5), 1292–1300.
• Watson, J.D., & Crick, F.H. (1953). Molecular structure of nucleic acids. Nature, 171(4356), 737–738.
• Valdatta, L., et al. (2004). Evaluation of the efficacy of polydeoxyribonucleotides in the healing process of autologous skin graft donor sites. Current Medical Research and Opinion, 20(3), 403–408.
• Kim, T.H., et al. (2019). Polydeoxyribonucleotide for treating skin photoaging. Dermatologic Surgery, 45(5), 670–678.
• Belletti, S., et al. (2007). Polydeoxyribonucleotide promotes cyclobutane pyrimidine dimer repair in UVB-exposed dermal fibroblasts. Photodermatology, Photoimmunology & Photomedicine, 23(5), 242–249.