Rejuran: Harnessing Polynucleotides for Advanced Skin Rejuvenation

Introduction

In the ever-evolving field of aesthetic medicine, innovative treatments continually emerge to address the complex challenges of skin aging. One such groundbreaking approach, gaining popularity in leading clinics from Seoul to Melbourne, is the use of polynucleotides (PN) derived from salmon DNA, commonly known as Rejuran. This article delves into the scientific foundations of this treatment, its mechanisms of action, clinical applications, and its potential to revolutionize skin rejuvenation strategies.

The Science of Polynucleotides

What are Polynucleotides?

Polynucleotides are long-chain DNA fragments extracted from salmon milt, which is the seminal fluid of male salmon [5]. This origin has led to the colloquial term “salmon sperm DNA” being used to describe the treatment. However, this terminology is not entirely accurate. While the DNA does indeed come from salmon reproductive material, it’s not specifically isolated from sperm cells but rather from the entire seminal fluid, which contains various cellular components and extracellular material.

These high-molecular-weight DNA chains, typically ranging from 50 to 1500 base pairs in length, form the basis of Rejuran and similar PN products [5]. The use of DNA in skincare might seem unconventional at first glance, but extensive research has demonstrated that these molecules possess remarkable properties that can significantly benefit human skin [5,6].

Molecular Structure and Function

The polynucleotides used in Rejuran are carefully extracted and purified to ensure their biocompatibility and efficacy. The DNA fragments are composed of nucleotides - the building blocks of DNA - which consist of a sugar (deoxyribose), a phosphate group, and one of four nitrogenous bases: adenine, guanine, cytosine, or thymine.

This molecular structure is crucial to the function of PNs in skin rejuvenation. The size of these DNA fragments (50-1500 base pairs) allows them to penetrate the skin effectively when injected intradermally. Once in the skin, these DNA fragments are thought to interact with various cellular receptors, triggering a cascade of biological responses that contribute to skin regeneration and repair.

Mechanism of Action

The efficacy of PN treatments like Rejuran is rooted in several key mechanisms:

1. Fibroblast Activation: PNs stimulate fibroblasts, the cells responsible for producing collagen and elastin. These proteins are crucial for maintaining skin elasticity and firmness [5]. Research has shown that PNs can increase fibroblast proliferation and migration, leading to enhanced extracellular matrix production [6]. This activation is believed to occur through the interaction of PNs with specific cell surface receptors, particularly the A2A purinergic receptors.

2. Hydration: PNs have a high water-binding capacity, contributing to skin hydration and plumping [5]. This is due to the hydrophilic nature of DNA molecules, which can attract and retain water molecules in the skin’s extracellular matrix. The improved hydration not only enhances skin appearance but also supports optimal cellular function and nutrient delivery.

3. Tissue Repair: They promote tissue repair and regeneration, potentially improving skin texture and reducing the appearance of fine lines [6]. This is achieved through the activation of repair pathways and the stimulation of growth factors. PNs have been shown to increase the production of growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), which play crucial roles in tissue repair and angiogenesis.

4. Anti-inflammatory Effects: Some studies suggest that PNs may have anti-inflammatory properties, which could be beneficial in treating various skin conditions [3]. This anti-inflammatory action is thought to be mediated through the modulation of cytokine production. Specifically, PNs have been shown to reduce the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

5. Antioxidant Properties: Recent research has indicated that PNs may also have antioxidant effects, helping to protect skin cells from oxidative stress and environmental damage [6]. This antioxidant activity is believed to be due to the ability of PNs to scavenge free radicals and upregulate the expression of antioxidant enzymes such as superoxide dismutase (SOD) and catalase.

6. ECM Remodeling: PNs have been shown to influence the remodeling of the extracellular matrix (ECM). They can modulate the activity of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), which play crucial roles in ECM turnover and skin structure maintenance.

7. Cell Survival Promotion: Studies have demonstrated that PNs can enhance cell survival under stress conditions. This cytoprotective effect is particularly relevant in the context of skin aging and environmental damage.

Clinical Applications

Rejuran and similar PN treatments have shown efficacy in addressing a wide range of skin concerns:

• Fine lines and wrinkles
• Uneven skin texture
• Skin laxity
• Impaired barrier function
• Atrophic acne scars
• Periorbital hyperpigmentation
• Photodamaged skin
• Melasma
• Enlarged pores [7]

The versatility of PN treatments makes them suitable for various facial areas, including delicate regions like the periorbital area. They can also be used on the neck, décolletage, and hands. In Melbourne clinics and worldwide, practitioners are exploring the use of PNs in combination with other treatments to enhance overall outcomes in comprehensive skin rejuvenation protocols.

Treatment Protocol

A typical Rejuran treatment involves multiple intradermal injections across the treatment area using a fine needle or cannula. The procedure is relatively quick, usually taking about 15-30 minutes [7]. For optimal results, a series of treatments is often recommended, typically spaced about 4 weeks apart [7].

Recent innovations in delivery methods have led to the development of specialized injection devices. For instance, some practitioners use an injector gun with multiple 34G sterilized needles, which can deliver PN more precisely and potentially reduce patient discomfort [7]. This device allows for consistent, evenly spaced injections, ensuring uniform distribution of the product across the treatment area.

Dosage and Concentration

The concentration of PNs in Rejuran and similar products can vary, but it’s typically in the range of 5-20 mg/ml [5]. The total dose per treatment session can range from 1-4 ml, depending on the treatment area and the specific concerns being addressed.

It’s important to note that the optimal dosage can vary based on individual patient factors such as age, skin condition, and treatment goals. Practitioners often tailor the treatment protocol to each patient’s needs, adjusting the concentration, volume, and number of treatment sessions as necessary.

Treatment Areas and Techniques

1. Face: For facial rejuvenation, PNs are typically injected into the dermis using a series of microinjections. The treatment often focuses on areas prone to fine lines and wrinkles, such as the forehead, periorbital region, and nasolabial folds.

2. Neck: When treating the neck, injections are usually more superficial to address skin laxity and fine lines without risking product migration.

3. Hands: For hand rejuvenation, PNs can be injected into the dorsum of the hands to improve skin quality and reduce the appearance of prominent veins and tendons.

4. Scalp: Some practitioners are exploring the use of PNs for scalp treatments, aiming to improve hair growth and quality.

Efficacy and Patient Satisfaction

Several studies have demonstrated the efficacy of PN treatments in skin rejuvenation. In a survey conducted among dermatologists, PN injections were reported as a highly popular “skin booster” treatment [7].

A study by Lee et al. (2022) compared the effects of PN and hyaluronic acid fillers on periocular rejuvenation. They found that both treatments improved skin hydration and elasticity, but PN showed superior results in improving skin texture and reducing fine lines [7]. The study used objective measures such as cutometry for skin elasticity and corneometry for hydration, providing quantifiable data on the improvements.

Another study by Jeong et al. (2020) investigated the efficacy of PN injections in treating crow’s feet. The researchers found significant improvements in wrinkle depth and skin elasticity after a series of PN treatments, with effects lasting up to 12 weeks post-treatment [7].

The effects of PN treatments are not just cosmetic but also functional. Patients have reported improvements in skin hydration, texture, and overall appearance. These subjective improvements are often corroborated by objective measures such as increased skin elasticity and hydration as measured by cutometry and corneometry [5].

Long-term studies on the effects of repeated PN treatments are still ongoing, but preliminary data suggest that regular treatments may lead to cumulative improvements in skin quality over time.

Safety Profile

While the concept of injecting fish DNA might raise concerns, Rejuran and similar PN products have demonstrated a favorable safety profile. The polynucleotides used are highly purified and biocompatible with human skin [5].

As with any injectable treatment, there can be mild side effects such as temporary erythema, edema, or ecchymosis at the injection sites. However, these typically resolve within a few days [7]. Serious adverse events are rare, but as with all cosmetic procedures, should be monitored and managed by qualified healthcare professionals.

It’s worth noting that despite the marine origin of the DNA, allergic reactions are extremely rare. This is likely due to the high purification process and the fact that DNA structure is highly conserved across species. The risk of immunogenicity is further reduced by the breakdown of the DNA into smaller fragments during the manufacturing process.

Some studies have investigated the potential for systemic absorption of injected PNs. Current evidence suggests that the majority of the injected material remains localized to the treatment area, with minimal systemic distribution [5].

Comparison with Other Skin Rejuvenation Treatments

While PN treatments offer unique benefits, it’s important to consider how they compare to other established skin rejuvenation treatments:

1. Hyaluronic Acid Fillers: Unlike HA fillers which primarily add volume, PNs work by stimulating the skin’s own regenerative processes. This can lead to more natural-looking, long-lasting results.

2. Platelet-Rich Plasma (PRP): Both PRP and PNs aim to stimulate skin regeneration, but through different mechanisms. PNs offer a more standardized treatment approach compared to the variability inherent in PRP preparations.

3. Laser Treatments: While lasers can effectively target specific skin concerns, PN treatments offer a more holistic approach to skin rejuvenation, potentially improving overall skin quality.

4. Chemical Peels: PNs work from within the skin, potentially offering more profound and longer-lasting results compared to superficial treatments like chemical peels.

Future Directions

As research in this field progresses, several exciting avenues are being explored:

1. Combination Therapies: Studies are investigating the potential synergistic effects of combining PN treatments with other modalities such as laser treatments, microneedling, or energy-based devices. For example, combining PNs with fractional laser treatment might enhance skin remodeling and collagen production.

2. Targeted Delivery Systems: Research is ongoing into developing more efficient delivery systems for PNs, potentially enhancing their penetration and efficacy. This includes the development of nanoparticle-based delivery systems and novel injection techniques.

3. Expanded Applications: While current use focuses primarily on facial rejuvenation, future applications may include body contouring, scar treatment, and hair restoration. Preliminary studies are exploring the use of PNs in treating stretch marks and promoting wound healing.

4. Long-term Effects: More long-term studies are needed to fully understand the duration of effects and any potential long-term benefits or risks of repeated PN treatments. Researchers are particularly interested in the cumulative effects of regular PN treatments on skin quality and the aging process.

5. Customized Formulations: There is ongoing research into developing PN formulations tailored to specific skin types or concerns. This could involve varying the length of DNA fragments or combining PNs with other active ingredients.

6. Topical Applications: While current PN treatments are injectable, researchers are exploring the potential for topical PN formulations. This could potentially make the treatment more accessible and suitable for at-home use.

7. Mechanism of Action Studies: Further research is needed to fully elucidate the molecular mechanisms underlying the effects of PNs on skin cells. This could lead to more targeted and effective treatment protocols.

Conclusion

Rejuran and other PN treatments represent an exciting frontier in skin rejuvenation. By harnessing the regenerative power of salmon DNA, these treatments offer a novel approach to improving skin quality and combating signs of aging. The ability of PNs to stimulate the skin’s own regenerative processes sets them apart from traditional fillers and offers the potential for more natural-looking, long-lasting results.

While more research is needed to fully elucidate their long-term effects, early results and high patient satisfaction rates suggest that PN treatments may play an increasingly important role in aesthetic medicine. From bustling clinics in Seoul to sophisticated practices in Melbourne, practitioners worldwide are incorporating these innovative treatments into their repertoire.

As with all cosmetic treatments, patients considering Rejuran or similar PN injections should consult with qualified healthcare professionals to determine if the treatment is appropriate for their individual needs and to ensure safe and effective administration. The future of PN treatments looks promising, with ongoing research likely to unlock even more potential applications and refine treatment protocols.

As our understanding of skin biology and the aging process continues to evolve, treatments like Rejuran that work in harmony with the body’s natural processes are likely to become increasingly important in the field of aesthetic medicine.

References

[3] Czumbel, L.M., et al. (2021). Hyaluronic Acid Is an Effective Dermal Filler for Lip Augmentation: A Meta-Analysis. Frontiers in Surgery, 8, 681028.

[5] Park, K.Y., et al. (2016). Long-chain polynucleotide filler for skin rejuvenation: efficacy and complications in five patients. Dermatologic Therapy, 29(1), 37-40.

[6] Galeano, M., et al. (2021). Polydeoxyribonucleotide: a promising biological platform to accelerate impaired skin wound healing. Pharmaceuticals, 14(11), 1103.

[7] Rho, N.K., et al. (2024). A survey on the cosmetic use of injectable polynucleotide: The pattern of practice among Korean Dermatologists. Journal of Cosmetic Dermatology, 23, 1243-1252.