Polynucleotide Injections vs Fillers: Doctor’s Guide to PN/PDRN Results, Safety & Best Uses

By Dr. Cosentino

Published: Sat, Oct 18/2025

“Clinician map of safe microdroplet points for PN injections around the cheeks and under-eye.”

Introduction

Polynucleotide injections—often labeled PN or PDRN—are gaining traction as regenerative “skin quality” treatments. Instead of simply adding volume, PN solutions aim to improve tone, texture, elasticity, and dermal health. In this clinician-led explainer, you’ll learn how PN works, ideal patient profiles, treatment planning and before/after guidance, and how outcomes compare with HA boosters, calcium hydroxylapatite (CaHA), and poly-L-lactic acid (PLLA) biostimulators. We’ll also outline U.S. regulatory status and risk management so your practice can evaluate PN evidence alongside proven filler options.

What are polynucleotide (PN/PDRN) injections?

Snippet: PN injectables deliver highly purified DNA fragments (commonly salmon-derived PDRN or synthesized PN) into the dermis to support tissue repair via adenosine A2A receptor signaling, angiogenesis, and fibroblast activity—translating to better hydration, elasticity, and fine-line softening over a series of sessions.

Details:

  • Composition & mechanism: PDRN/PN comprises DNA fragments (≈50–1500 kDa) that act as pro-healing biologics rather than volumizers. Evidence suggests activation of adenosine A2A receptors, increased cAMP/CREB signaling, downstream VEGF expression, and anti-inflammatory effects—all conducive to angiogenesis and matrix remodeling.

  • Clinical effect profile: Small clinical studies and reviews report improvements in skin elasticity, hydration, and texture, especially in photoaged or delicate areas (e.g., periorbital). Robust, large RCTs are still limited; set expectations accordingly.

Further reading (external medical source): See this peer-reviewed overview of PDRN as a skin anti-aging agent for mechanism and early clinical data.
Polydeoxyribonucleotide: A promising skin anti-aging agent. ScienceDirect

Who is a good candidate?

Snippet: Ideal candidates want better skin quality (glow, fine-line smoothness, bounce) rather than lift or contour; they accept a series approach and gradual change, and they’re appropriate for biostimulatory therapies.

Details:

  • Common indications: early photoaging, crepiness/thin dermis (periorbital, neck), mild acne scarring, and “tired-skin” complaints where hydration/elastin support are priorities.

  • Good-fit profiles: Fitzpatrick I–VI with realistic expectations; patients who already maintain skin health (SPF, retinoids) and want an adjunct to energy-based or topical regimens.

  • Relative poor fits: patients seeking instant volumization, sharp contour, or single-session transformations—these needs favor HA, CaHA, or PLLA (see comparison below).

  • Contraindications & cautions: active infection/dermatitis at the site, pregnancy/breastfeeding (insufficient safety data), autoimmune flares, known hypersensitivities to excipients, and anticoagulation risks per standard injectable screening. (Follow your jurisdiction’s guidance and product IFUs.)

Safety and regulation (U.S., EU/UK): what clinicians must know

Snippet: In the U.S., PN/PDRN injectables are not FDA-approved as dermal injectables as of today; many products seen on social media are unapproved for injection and should not be used in U.S. clinical practice. In the EU/UK, some PN devices carry CE marking under medical-device rules; verify classification and conformity for each brand.

Details:

  • United States: Most PN/PDRN solutions marketed for injection lack FDA approval for that route/indication. U.S. providers injecting non-approved PN products risk FDA enforcement and liability. Topical PN serums marketed strictly for cosmetic appearance without systemic effect may fit cosmetic categories, but aesthetic injectables are different.

  • EU/UK: Some PN injectables are CE-marked medical devices; classification and scrutiny vary (often Class III for implantable/injectable aesthetics), requiring notified-body review and clinical evaluation. Always verify the specific device’s certificate and IFU before purchase.

  • What is FDA-approved for skin quality? SKINVIVE™ by JUVÉDERM® (non-crosslinked HA microdroplet) is FDA-approved to improve cheek skin smoothness in adults—useful as a U.S. benchmark when discussing “skin boosters.”

Practical compliance tip: Build a formulary limited to FDA-cleared/approved injectables for U.S. practice. Educate patients who ask about “polynucleotides” that, domestically, you offer evidence-based alternatives (e.g., HA microdroplets, dilute CaHA, PLLA) with established labeling.

Treatment protocol and before/after guidance

Snippet: PN is typically delivered as intradermal micro-aliquots or fanning with a cannula over 2–3 sessions, spaced 2–4 weeks apart. Expect subtle, progressive improvements lasting roughly 6–9 months (protocol- and product-dependent), with low downtime but common transient erythema/edema.

Before (consult & planning):

  • Assess intent: “Skin looks dull/crepey” vs “I want lift.” If lift/contour is primary, consider HA/CaHA/PLLA first.

  • Baselines: standardized photos (front/obliques), close-ups of texture, melanin/erythema imaging if available.

  • Informed consent: Explain regulatory status (for U.S.), expected course of sessions, and gradual nature of change; discuss alternatives. Keep language specific (e.g., “texture and elasticity,” not “tightening”).

  • Prime the canvas: emphasize sun protection, topical retinoids (as tolerated), and spacing from resurfacing/energy procedures to minimize compounding inflammation.

During (technique notes):

  • Depth: superficial dermis; microdroplet “bleb” method or linear threading with 30–34G needles; periorbital requires ultra-conservative volumes and expertise.

  • Volumes: modest aliquots per zone; avoid over-treating; consider staged plans.

  • Adjuncts: pair with HA microdroplets or hyper-dilute CaHA in appropriate regions for synergistic collagen support—provided each product’s labeling and best practices are followed.

After (care & follow-up):

  • Immediate: cold compress PRN, avoid heat/exertion 24 hours, no makeup on puncture sites same day.

  • Follow-up: review at 2–4 weeks; reinforce skincare; schedule next session; re-photo for texture/elasticity.

  • Longevity: counsel 6–9 months as a working range pending device and patient factors; plan maintenance 1–2×/year if continuing PN, or transition to HA/CaHA/PLLA for structural goals.

How polynucleotide injections compare to HA boosters, CaHA, and PLLA

Snippet: PN aims at skin quality via biologic repair; HA boosters hydrate/smooth; CaHA and PLLA are biostimulatory fillers that improve quality and structure with longer durability. Select by goal (quality vs structure), onset, durability, and regulatory status. Empire On-Demand teaches collagen-boosting biostimulators if you're a physician, dentist, or nurse looking to learn these increasingly popular procedures.

Mechanisms at a glance

  • PN/PDRN: pro-healing DNA fragments → A2A receptor, VEGF, anti-inflammatory signaling → dermal repair/elasticity. Gradual.

  • HA boosters (e.g., SKINVIVE™): non-crosslinked HA microdroplets → hydration and smoothness in the cheeks; FDA-approved in the U.S. for skin smoothness (cheeks). Subtle; ~6 months.

  • CaHA (Radiesse®): CaHA microspheres in CMC gel → immediate scaffold + collagen/elastin neogenesis; FDA-approved for NLFs and dorsum hand augmentation; off-label hyper-dilute protocols target skin quality. Durability often ≥12 months.

  • PLLA ( Sculptra®): PLLA microparticles → fibroblast activation and collagen deposition over months; FDA-approved for facial wrinkles (e.g., NLFs); onset delayed, longevity up to 2+ years after series.

Outcomes & timelines (clinically useful summary)

  • PN/PDRN: Texture, elasticity, “glow,” and fine-line softening; series of sessions, results accumulate and can persist roughly 6–9 months (evidence base still maturing).

  • HA boosters: Immediate hydration and smoother skin quality; FDA-labeled U.S. option (cheek smoothness) with ~ 6-month duration.

  • CaHA: Subtle immediate support with biostimulation for quality + structure; common maintenance annually or longer; growing literature for dilute/hyper-dilute skin-quality protocols.

  • PLLA: Minimal early change, then progressive firming/volumization as collagen builds over 3–6 months; durability up to 2 years or more post-series.

Safety & regulation

  • PN: U.S. not FDA-approved for injection; avoid unapproved PN injectables domestically. CE-marked options exist in other markets—vet certificates and IFUs.

  • HA, CaHA, PLLA: Multiple FDA-approved options with well-documented labeling, IFUs, and post-market surveillance.

Case-based decision guide (doctor-led)

Snippet: Match goal and anatomy to the right tool, then sequence biostimulators thoughtfully.

Case 1 – Periorbital crepiness in a 42-year-old runner

  • Goal: texture/elasticity; no volume.

  • Plan: If outside U.S. where CE-marked PN is available, consider PN microdroplets across malar/periorbital zones in 2–3 sessions with conservative aliquots. In the U.S., favor HA microdroplets (SKINVIVE-class for cheek skin quality) and topical/energy adjuncts.

Case 2 – Lower-face laxity with etched NLFs in a 52-year-old

  • Goal: structure + quality.

  • Plan: Hyper-dilute CaHA for dermal stimulation and skin quality; targeted HA for fold support. Space sessions 4–8 weeks; reassess collagen response at 3–4 months.

Case 3 – Midface deflation, “tired” look in a 58-year-old

  • Goal: lifting effect that lasts.

  • Plan: PLLA series (e.g., 2–3 sessions) for collagen remodeling and durability; blend with HA touch-ups for focal highlights while PLLA matures.

Practical protocol pearls

Snippet: PN is a skin-quality tool; HA/CaHA/PLLA manage quality + shape. Sequence from foundation → finish.

  • Sequence smartly: Build foundation with PLLA/CaHA when structure is lacking; finish with HA microdroplets for radiance.

  • Dose conservatively: Biostimulators work over time—avoid over-treating early.

  • Measure what matters: Use texture/elasticity scores, standardized lighting, and patient-reported outcomes (“makeup sits better,” “less crepe”).

  • Educate on evidence: PN is promising but evidence base is younger than HA/CaHA/PLLA; contrast this with Skinvive’s FDA labeling to clarify expectations in the U.S. market.

Market momentum (why patients keep asking)

Snippet: Patient demand is rising globally—search and social interest plus early clinical adoption in Europe/Asia—while analysts forecast double-digit CAGR through 2034 for PN injectables. In the U.S., conversations often pivot to FDA-approved skin boosters instead.

Internal resources

FAQs

Are polynucleotide injections the same as fillers?

No. PN/PDRN primarily targets skin quality and repair, not volume. Fillers like HA, CaHA, and PLLA either hydrate/smooth (HA) or biostimulate for structure and long-term collagen (CaHA/PLLA).

Are PN injectables FDA-approved in the U.S.?

As of October 16, 2025, PN/PDRN injectables are not FDA-approved for injection in the U.S. Using unapproved PN injectables may expose providers to enforcement risk. Consider FDA-approved alternatives (e.g., HA microdroplets for cheek skin smoothness).

How many PN sessions are typical, and how long do results last?

Common protocols use 2–3 sessions spaced 2–4 weeks apart; observed improvements can persist ~6–9 months, then require maintenance—recognizing product and patient variability.

What makes HA “skin boosters” different from standard HA fillers?

SKINVIVE™ represents FDA-labeled HA microdroplet therapy for cheek skin smoothness, emphasizing hydration and texture rather than contour. Traditional HA fillers are crosslinked gels for shape/volume.

Can PN be combined with lasers, RF microneedling, or peels?

Yes, but sequence thoughtfully to avoid cumulative inflammation. Many clinicians stage energy-based work first, allow recovery, then add PN/HA microdroplets. (Follow device and product IFUs.)

Is hyper-dilute CaHA really a “skin quality” treatment?

Evidence and expert practice support dilute/hyper-dilute CaHA for dermal biostimulation and skin quality, in addition to its volumizing indications.

How does PLLA compare on longevity?

After a series, PLLA improvements often build over 3–6 months and may last up to 2 years or more—longer than HA boosters and typically longer than PN reports.

What are the most common adverse events with PN?

Similar to other microinjections: transient erythema, edema, tenderness, pinpoint bruising. Serious events are uncommon when products are properly regulated and technique is sound; data are still developing—use approved alternatives in the U.S.

Does PN help acne scars?

Early evidence and clinical experience suggest modest gains in texture and elasticity, useful as part of multimodal scar care; stronger evidence exists for HA/energy-based combinations.

What do you tell patients who ask for “salmon DNA injections”?

Clarify that U.S. practices should stick to FDA-approved injectables. For “skin quality,” consider HA microdroplets; for structure + quality, consider CaHA or PLLA—then revisit PN if and when approved locally.

Conclusion

Bottom line: Polynucleotide injections are a promising regenerative tool for skin quality—but U.S. adoption hinges on regulatory pathways and more high-quality trials. Right now, you can deliver similar or superior patient value by matching goals to mechanisms: HA microdroplets (hydration/smoothness), CaHA (biostimulation + structure), and PLLA (durable collagen remodeling). Ready to sharpen technique, safety, and outcomes?

Upgrade your skills with Empire On-Demand. Stream expert-led modules on HA skin boosters, hyper-dilute CaHA, and PLLA—including patient selection, mapping, dilution math, and complication management—so you can offer the right treatment, for the right patient, at the right time.

Thanks for contacting us. We'll get back to you as soon as possible.
By Stephen Cosentino
Mar 04, 2025

Most of us have experienced that slightly sinking sensation when we look in the mirror and spot the signs of aging. Whether it's the appearance of new or deepening wrinkles, loose skin, or the loss of your jawline, aging is a natural process (even if its effects aren't always welcome!)

Dealing With the Signs of Aging

At Empire Medical Training, we believe it's important to celebrate your natural beauty and be confident in yourself. Aging is a gift in so many ways, but we also understand that not everyone feels their best when their appearance changes. 

And, if you've not always applied your SPF, eaten well, slept deeply, or generally invested in your self-care, you may find that the signs of aging are hitting a little faster than you'd like! 

The Challenge of Modern Life and Aging

We all live busy and stressful lives, and it shows in our faces, especially when this stress is combined with other environmental factors such as pollution, UV (not just from the sun, but also from digital devices), and second-hand smoke, even if we don't smoke ourselves.

Embracing Aging... Your Way

The good news is, that there are so many ways to tackle the signs of aging, whether you're interested in lip augmentation, a cheek lift, or jawline contouring. Search for 'fillers near me' and you'll find so many options. 

But it's vital that you choose a highly skilled and accredited aesthetics practitioner who knows how to integrate surgical and non-surgical practices to deliver the best, tailored results for your unique needs, preferences, and situation.

We'll cover this more shortly, but for now, let's take a look at the fascinating topic of nonsurgical facelifts. Firstly, what is a nonsurgical facelift, and how is it different from a traditional plastic surgery facelift?

Why plastic surgery facelifts are less popular

A lot of people reach an age where they feel that the signs of aging are coming thick and fast, and what they see in the mirror doesn't reflect how they feel inside! 

But at the same time, the risks of traditional plastic surgery - correctly called a rhytidectomy - can be significant, and this type of aesthetic work can also be very expensive.

Let's be honest too, most of us have seen people who have received a traditional plastic surgery facelift and the results are very obvious, especially if they have had more than one facelift. 

Traditional plastic surgery facelifts are permanent but they tend to need renewing every few years as the effects of age continue. They are medical procedures with clear risks and if they are carried out poorly, they can leave side effects such as physical scarring (or worse.)

The rise of non surgical facelifts

Because many people were concerned about the dangers of traditional plastic surgery facelifts, and the many risks associated with a 'facelift gone wrong' (from unnaturally taut results that change the individual's appearance to medical complications), aesthetics industries have developed an alternative, which is generally known as the non surgical facelift.

If you love the thought of minimally-invasive aesthetics procedures, tailored for jawline contouring, cheek lifting, or lip augmentation, the non surgical facelift might be the aesthetics treatment for you!

What is a non surgical facelift in aesthetics?

A nonsurgical facelift is an aesthetic procedure that is only very minimally invasive. However, it delivers excellent results that are comparable to traditional plastic surgery, and it can be tailored or combined with other services, such as fillers, to deliver clear and desired effects (lip augmentation, a cheek lift, or jawline contouring, for example.)

Nonsurgical facelifts are also less expensive than plastic surgery facelifts, they have shorter recovery times and they also have fewer side effects overall. However, because this kind of aesthetic treatment is non-surgical, it is temporary. 

How long does a nonsurgical facelift last? 

A non surgical facelift will usually last from around 3-4 months to perhaps two years, depending on the treatment, the patient, and the individual factors involved.

For most people though, especially anyone already searching for 'fillers near me' the prospect of a nonsurgical facelift is highly appealing. Let's take a closer look at what you need to know. 

How effective are nonsurgical facelifts?

Non surgical facelifts are an aesthetic treatment that can be used to achieve specific results for problem areas. For example, your aesthetic practitioner might combine a thread lift, or cheek lift, use Botox for lip augmentation and jawline contouring, and inject dermal fillers to add volume back into areas of your face for a youthful, plump finish.

Can nonsurgical facelifts be used for all aesthetic goals?

No, these 'light touch' procedures are less effective for more serious aesthetic complaints, or situations where the client wants a permanent change to his or her face.

If you are concerned about widespread sagging skin (perhaps for example if you have lost a lot of weight, or have sun damage), or if you have very deep facial creases (perhaps from stress, genetics, smoking, or other underlying factors), traditional plastic surgery may be the best route.

In all instances, the first point is to discuss your concerns and the possibilities for aesthetic treatment with a skilled aesthetics professional with the right qualifications, training, experience, and certification. 



Why you must use highly skilled aesthetics practitioners 

The skill of the aesthetics practitioner will very much determine the results of a nonsurgical facelift, as this combination treatment requires expertise, professional judgment, experience, and deep knowledge of the various aesthetics procedures that can be applied for the best possible results. 

For this reason, at Empire Medical Training, we never recommend simply searching for 'fillers near me', or 'Botox near me', to find your nearest beautician without establishing their professional credentials, certifications, and insurance. 

As a leading national provider of CME for the aesthetics industry, we can provide you with information on highly skilled and certified aesthetics professionals in your area. 

Please contact us for more information or find out more about the courses we offer to see the quality of our offer and the credentials of our faculty. After all, when you're dealing with your face, you can't leave anything to chance!

Why Are Nonsurgical Facelifts Less Risky than Traditional Plastic Surgery Facelifts?

Traditional plastic surgery facelifts require a general anesthetic. This is inherently risky but it is required because the surgery involves deep incisions. These incisions are also riskier because, as surgical sites, they will require full healing and there is always a risk of infection. 

Why Are Non Surgical Facelifts Less Expensive than Traditional Plastic Surgery Facelifts?

Nonsurgical facelifts are cheaper than surgical facelifts for a number of reasons:

  1. Plastic surgery facelifts must be performed by a board-certified plastic surgeon. Nonsurgical facelifts can be performed by aesthetics professionals.
  2. Nonsurgical facelifts don't require an operating suite or an overnight stay. They can be performed in your aesthetic practitioner's offices, and you can go home immediately afterward. 
  3. Nonsurgical facelifts do not require a team of support staff to aid the procedure or recovery
  4. Nonsurgical facelifts have a shorter recovery team and require less of a follow-up than a traditional plastic surgery facelift. 



Is There One Type of Nonsurgical Facelift?

No, and this is the beauty of this aesthetic procedure! When you work with a skilled practitioner, you can combine treatments to achieve the effect of a full facelif, but with different minimally or non-invasive procedures to achieve your desired looks. 

For example, you might have hyaluronic acid to achieve a cheek lift, and Botox for lip augmentation and jawline contouring, with a chemical peel for a completely refreshed and rejuvenated appearance across your entire face. 

You also can (and most likely will) have different procedures done at different times, so that the effects are gradually layered for the best results. This also creates a more subtle finish that doesn't surprise people with a sudden severe change in your appearance!

What Are the Most Popular Types of Nonsurgical Facelift?

From botox to fat injections, a good aesthetics practitioner will have various tools and techniques on offer to deliver that look you hope for.

At Empire Medical Training we constantly invest in the latest training for all current and emerging aesthetics protocols and technologies, so our graduates are at the cutting edge of this exciting industry. 

The three types of nonsurgical facelifts are typically the most popular:

Thread Lifts for a Cheek Lift and Jawline Contouring

If you have loose skin in your cheeks, eyes, forehead, or chin, a thread lift (also known as a barbed thread lift or PDO thread lift depending on the medical thread used), can be highly effective. This procedure will stimulate elastic and collagen production whilst simultaneously tightening the treated area. 

The production of new collagen and elastin will work over the course of a few months to restore lost volume naturally and gradually, and the overall effects of the thread lift will typically last for 1-2 years.

Because of the gradual improvement, clients who have aesthetics thread lifts usually say that friends, colleagues, and loved ones ask them what their secret is because the results are effective but subtle and gradual. 

Botox Injections (Neuromodulator Injection)

Search for 'Botox near me' and you will find endless local listings because Botox is so incredibly popular! Botox and other branded neuromodulation drugs relax overactive muscles to smooth out fine lines. 

This is a quick and simple in-clinic procedure with low risks, so long as it is performed by a skilled and certified aesthetics professional. 

The results don't last as long as with a thread lift, but it's very easy to get targeted Botox touch-ups when you need them, with minimal downtime (many people nip in to get a Botox session on their lunch break!) 

Botox is also affordable and skilled practitioners can even use it to change the contours of a person's face, for example, to straighten a nose, or for jawline contouring, as well as to soften laughter lines and frown lines.

Dermal Filler Injections

Dermal fillers are also called soft tissue fillers, and these highly popular aesthetic procedures restore volume to hollow or sagging areas of the face. For example, they can be used for lip augmentation or to create fuller cheeks. Hyaluronic acid is the most common type of dermal filler, but other types include PMMA and calcium hydroxylapatite and PMMA.

When delivered by a skilled dermal filler practitioner, the results can be superb, and depending on the filler chosen, can last for six months to several years.

Again, as with thread lifts and Botox, dermal fillers have low risks and side effects. However, because they involve injections, it's important to choose a certified provider who has completed an accredited dermal filler training course, and who continues to invest in their CME.

At Empire Medical Training, our aesthetic graduates are committed to becoming the finest practitioners in their chosen fields. Fully certified, highly skilled, and trained by incredibly respected faculty, our students undertake comprehensive training to offer their clients the best possible results. Why not browse our course list to find out more?

Speak to the Aesthetic Training Experts

Our friendly team is always here to answer any questions you might have about aesthetic training, aesthetic procedures, and the industry in general. Whether you're looking for a trusted practitioner or considering an aesthetic career yourself, talk to us for advice you can trust.