Polynucleotides in Aesthetic Medicine: A Critical Review of Mechanisms, Clinical Evidence and Future Applications
Abstract
The demand for regenerative aesthetic treatments has increased significantly over the last decade, reflecting a shift away from purely volumising interventions towards therapies capable of improving tissue quality, hydration, elasticity and long-term skin health. Polynucleotides (PNs) have emerged as one of the most promising regenerative treatments within aesthetic medicine due to their ability to stimulate cellular repair, enhance extracellular matrix remodelling and support dermal regeneration. Derived from highly purified DNA fragments, commonly sourced from salmon or trout DNA, polynucleotides are increasingly used for facial rejuvenation, periocular revitalisation, scar management, skin quality improvement and hair restoration. This review synthesises current scientific evidence from systematic reviews, clinical trials, consensus statements and observational studies to evaluate the efficacy, safety and regenerative potential of polynucleotide therapy. The evidence demonstrates consistent improvements in skin hydration, elasticity, collagen synthesis and overall skin quality, accompanied by a favourable safety profile and high patient satisfaction. While further large-scale randomised controlled trials are required to standardise treatment protocols, the current literature strongly supports the positive role of polynucleotides as a regenerative treatment modality in modern aesthetic medicine.
Introduction
Aesthetic medicine is increasingly focused on regenerative approaches that improve tissue quality rather than simply replacing volume or reducing wrinkles. Contemporary patients seek natural-looking outcomes, healthier skin and long-term improvements rather than dramatic structural changes. Within this context, polynucleotides have become one of the fastest-growing treatment categories in aesthetic medicine.
Polynucleotides are highly purified chains of nucleotides that act as biological stimulators of tissue repair and regeneration. Research suggests that they promote fibroblast activity, stimulate collagen synthesis, improve angiogenesis, reduce inflammation and support extracellular matrix remodelling (Lee et al., 2024). These mechanisms position polynucleotides within the broader field of regenerative aesthetics, which seeks to restore tissue function and quality through activation of endogenous healing pathways.
The growing popularity of products such as Rejuran®, PhilArt®, Plinest® and other polynucleotide-based injectables reflects increasing clinical confidence in their ability to improve skin quality while maintaining a natural appearance. Recent reviews have highlighted their potential applications in facial rejuvenation, periocular treatment, acne scar management, hair restoration and prevention of age-related skin deterioration (Lampridou et al., 2025; Lee et al., 2024).
Biological Mechanisms of Action
The regenerative effects of polynucleotides are believed to arise from multiple biological pathways. Polydeoxyribonucleotide (PDRN), a closely related compound frequently discussed alongside polynucleotides, has been shown to stimulate adenosine A2A receptors, leading to increased vascular endothelial growth factor (VEGF) production and enhanced angiogenesis. This promotes improved blood supply, oxygenation and tissue repair (Lee et al., 2024). (MDPI)
A second mechanism involves the salvage pathway, whereby degraded DNA fragments provide nucleotide substrates for cellular repair and DNA synthesis. This process supports fibroblast proliferation and regeneration of damaged tissues. Enhanced fibroblast activity subsequently increases production of collagen, elastin and hyaluronic acid, all of which are essential components of youthful and healthy skin. (MDPI)
Additional research suggests that polynucleotides exert anti-inflammatory and antioxidant effects, reducing oxidative stress and creating an environment more conducive to tissue repair. These properties distinguish polynucleotides from traditional dermal fillers, which primarily provide structural support rather than biological regeneration. (MDPI)
Clinical Applications in Aesthetic Medicine
Facial Rejuvenation
The strongest evidence for polynucleotide use relates to facial rejuvenation and skin quality enhancement. Multiple studies demonstrate improvements in skin elasticity, hydration, texture and radiance following treatment.
A comprehensive review by Lee et al. (2024) concluded that polynucleotides consistently improve skin texture, reduce wrinkle depth and enhance overall facial appearance. Improvements were attributed to increased collagen production, enhanced tissue hydration and improved extracellular matrix function. (MDPI)
Similarly, Lampridou et al. (2025) conducted a systematic review involving 219 patients and found statistically significant improvements in wrinkle reduction, skin texture and elasticity. The review also reported moderate to high patient satisfaction rates and a favourable safety profile. (Wiley Online Library)
Periocular Rejuvenation
The periocular region presents unique treatment challenges due to its thin skin and susceptibility to ageing. Polynucleotides have shown particular promise in this area because they improve tissue quality without creating excess volume.
Clinical studies have demonstrated improvements in crow’s feet, skin thickness, elasticity and overall periocular appearance. Unlike traditional fillers, which may risk oedema or contour irregularities, polynucleotides improve the underlying biological quality of the tissue, resulting in more natural outcomes.
Neck and Décolletage Rejuvenation
Ageing of the neck and décolletage is characterised by thinning skin, reduced elasticity and photodamage. Polynucleotide treatments have shown favourable outcomes in these regions, improving skin texture, firmness and hydration.
Recent real-world data involving 66 patients treated with Polynucleotides High Purification Technology (PN-HPT) demonstrated moderate to marked improvements in over 90% of neck treatments and almost 90% of décolletage treatments. Patient satisfaction exceeded 97%, with no serious adverse events reported.
Acne Scar Management
Regenerative stimulation of collagen production makes polynucleotides attractive for acne scar treatment. Clinical evidence suggests improvements in scar texture, depth and overall skin smoothness. Enhanced fibroblast activity and extracellular matrix remodelling contribute to gradual scar improvement while maintaining a low complication rate.
Hair Restoration
Emerging evidence indicates that polynucleotides may support hair growth through improved vascularisation, enhanced follicular environment and reduction of inflammatory processes. Although evidence remains less robust than for facial rejuvenation, early studies suggest potential benefits when incorporated into comprehensive hair restoration programmes. (MDPI)
Safety and Tolerability
One of the most compelling advantages of polynucleotide therapy is its excellent safety profile. Across multiple studies, adverse events are generally mild, transient and self-limiting.
Common side effects include temporary erythema, swelling, bruising and injection-site discomfort. Serious complications are exceedingly rare. The systematic review by Lampridou et al. (2025) reported only mild and transient adverse effects, with overall patient satisfaction ranging from moderate to high. (Wiley Online Library)
The recent real-world assessment by Eliana et al. (2026) further supported the safety of polynucleotides, reporting no serious adverse events and patient satisfaction rates approaching 100%.
The biocompatibility of purified DNA fragments contributes significantly to their tolerability. Unlike some synthetic biomaterials, polynucleotides integrate naturally within tissue repair processes, reducing the likelihood of adverse immune reactions.
Critical Evaluation of the Evidence
Although the evidence supporting polynucleotides is overwhelmingly encouraging, scientific rigour requires acknowledgement of current limitations.
The systematic review by Webb et al. (2024) identified 16 clinical studies involving approximately 750 participants and concluded that polynucleotides possess significant regenerative potential. However, the authors highlighted inconsistencies regarding molecular characterisation, dosing protocols and outcome measurements. (Springer)
Similarly, Lampridou et al. (2025) noted heterogeneity among studies and called for larger, high-quality randomised controlled trials. Despite these limitations, the review still concluded that polynucleotides represent a promising and effective treatment modality within aesthetic medicine. (Wiley Online Library)
Importantly, the limitations identified in current literature primarily concern standardisation and optimisation rather than evidence of ineffectiveness. The overwhelming trend across published studies demonstrates consistent clinical improvement and high patient satisfaction.
Synthesis of Current Evidence
When the available evidence is considered collectively, several conclusions emerge.
First, polynucleotides consistently improve skin quality parameters, including hydration, elasticity, texture and radiance.
Second, their regenerative mechanism differentiates them from conventional fillers by targeting biological repair rather than simple volume replacement.
Third, treatment outcomes appear particularly favourable in areas traditionally difficult to treat, including the periocular region, neck and décolletage.
Fourth, patient satisfaction is consistently high across studies, reflecting the natural and progressive improvements achieved through treatment.
Finally, the safety profile of polynucleotides compares favourably with many other injectable aesthetic treatments.
The convergence of mechanistic, clinical and real-world evidence strongly supports the integration of polynucleotides into contemporary aesthetic practice.
Future Directions
Future research should focus on standardising treatment protocols, identifying optimal dosing strategies and conducting larger randomised controlled trials. Comparative studies evaluating polynucleotides against other regenerative therapies, including platelet-rich plasma, exosomes and collagen biostimulators, would further clarify their role within regenerative aesthetics.
As understanding of tissue regeneration continues to evolve, polynucleotides are likely to become increasingly integrated into multimodal treatment strategies combining skin quality improvement, collagen stimulation and long-term tissue health.
How Kriniko Medical Aesthetics Can Help
Kriniko Medical Aesthetics is well positioned to deliver advanced regenerative aesthetic treatments using evidence-based polynucleotide protocols. By combining detailed facial assessment, personalised treatment planning and clinically proven regenerative therapies, Kriniko Medical Aesthetics can help patients achieve healthier, more youthful and naturally rejuvenated skin.
Polynucleotide treatments at Kriniko Medical Aesthetics may be used to improve skin hydration, elasticity and texture, reduce fine lines, support periocular rejuvenation, enhance neck and décolletage quality and complement other aesthetic procedures. The regenerative nature of polynucleotides aligns with the clinic’s commitment to achieving subtle, natural-looking outcomes that prioritise long-term skin health over short-term correction.
Through comprehensive consultation and bespoke treatment programmes, Kriniko Medical Aesthetics can help patients benefit from one of the most promising regenerative innovations currently available in aesthetic medicine.
Conclusion
Polynucleotides represent a significant advancement in regenerative aesthetic medicine. The current body of evidence demonstrates meaningful improvements in skin quality, elasticity, hydration and overall rejuvenation while maintaining an excellent safety profile. Their ability to stimulate biological repair processes rather than simply provide volume correction reflects the broader evolution of aesthetic medicine towards regenerative and restorative treatment approaches.
Although further research is required to establish standardised protocols and optimise treatment strategies, the existing literature consistently supports the positive clinical value of polynucleotides. Systematic reviews, consensus statements, observational studies and mechanistic investigations collectively indicate that polynucleotides are effective, well tolerated and capable of delivering natural-looking rejuvenation.
As regenerative aesthetics continues to develop, polynucleotides are likely to remain at the forefront of evidence-based treatments aimed at improving skin health, tissue quality and long-term aesthetic outcomes.
Reference List
Barbosa, A.P. (2026) ‘Regeneration in Aesthetic Medicine: Mechanisms, Evidence, and Clinical Boundaries’, Journal of Cosmetic Dermatology, 25, e70669.
Cavallini, M., Bartoletti, E., Maioli, L., Massirone, A., Palmieri, I.P., Papagni, M., Priori, M. and Trocchi, G. (2021) ‘Consensus report on the use of PN-HPT™ (Polynucleotides Highly Purified Technology) in aesthetic medicine’, Journal of Cosmetic Dermatology, 20(3), pp. 922–928.
Eliana, L., Perna, A., Bizzarri, S., Santoro, C., Cerutti, L., Dybala, A., Brunoro, A., Boffi, L., Prussia, C. and Saretta, S. (2026) ‘A Real-Life Assessment of Injectable Polynucleotides High Purification Technology in Aesthetic Medicine for Skin Rejuvenation’, Journal of Cosmetic Dermatology, 25, e70532.
Lampridou, S., Bassett, S., Cavallini, M. and Christopoulos, G. (2025) ‘The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review’, Journal of Cosmetic Dermatology, 24, e16721.
Lee, K.W.A., Chan, K.W.L., Lee, A., Lee, C.H., Wan, J., Wong, S. and Yi, K.H. (2024) ‘Polynucleotides in Aesthetic Medicine: A Review of Current Practices and Perceived Effectiveness’, International Journal of Molecular Sciences, 25(15), 8224.
Webb, W.R., Rahman, E., Rao, P., Abu-Farsakh, H.N., Yu, N., Garcia, P.E., Ioannidis, S., Sayed, K., Tam, E., Philipp-Dormston, W.G., Najlah, M., Rahman, Z., Carruthers, J.D.A. and Mosahebi, A. (2024) ‘Points to Ponder on the Role of Polynucleotides in Regenerative and Aesthetic Medicine: A Systematic Review’, European Journal of Plastic Surgery, 47, 66.
Supporting evidence for the paper was drawn from the uploaded studies and recent systematic reviews. Key findings regarding improvements in skin quality, hydration, elasticity, patient satisfaction and regenerative mechanisms are supported by the current literature. (Springer)
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