Rejuran HB PLUS: what a polynucleotide skin booster does, and what it does not

DNA is a chain of nucleotides. Cut and purify that chain to a particular length and you have a polynucleotide (PN); cut it shorter and the same family of material is usually called PDRN. Both are obtained from the gonads of salmonid fish, where DNA is unusually abundant, and both go through a purification sequence — lysis, filtration, endotoxin removal, chromatography, sterilisation — that strips out protein and leaves the nucleic acid behind.

One caution worth stating plainly: there is no agreed molecular-weight boundary between PN and PDRN. A 2025 cutoff has been proposed in the literature, but reviews published the same year note that no standardised criteria exist and that the two terms have been used interchangeably to the point of confusion. Any source that gives you a precise dividing number is being more confident than the field is.

How it is thought to work

In the dermis, PN forms a porous, viscous three-dimensional mesh that holds water. The prevailing explanation is that this scaffold restores viscoelasticity and gives fibroblasts a physical substrate to work against, encouraging matrix production.

It is worth being honest about the limits of that explanation. The mechanism of action of PN in human skin has not been established. A 2024 review states there is no objective data on it, and that the assumption PN behaves like PDRN — whose adenosine A2A receptor pathway is comparatively well characterised — remains a hypothesis rather than a demonstrated fact. Even for PDRN, blocking the A2A receptor reduces but does not abolish the effect, which means something else is also going on.

What is reproducible is the laboratory picture: human dermal fibroblast proliferation increases, COL1A1 and COL3A1 expression rises, and inflammatory signalling falls. Animal wound models show measurable increases in type I and type III collagen. Translating that into a promise about a human face is a larger step than most marketing copy admits.

Rejuran is a product line, not a single item, and the names are close enough to be confusing. What separates them is what has been added alongside the polynucleotide.

The manufacturer's own stated reason for adding lidocaine to HB PLUS is less painful treatment compared with the original Rejuran. That is a useful admission: discomfort with this treatment is real, not imagined, and formulation choice is the main lever against it.

No version is simply better than another. HB PLUS is the sensible default for thin, sensitive areas such as the periorbital skin, for patients with a low pain threshold, and for anyone who needs to complete a multi-session course without dreading each appointment.

Rejuran is routinely grouped with collagen stimulators such as PCL, PLLA and CaHA. The goals overlap; the biology does not.

A collagen stimulator introduces material the body recognises as foreign. Macrophages and fibroblasts are recruited to the site, and new collagen is laid down in the course of that response. It is a deliberate, controlled inflammatory reaction. The effect is larger and lasts longer — and delayed nodules and granuloma are recognised complications of that same mechanism.

Rejuran does not work this way. It does not depend on a foreign-body response. The trade-off runs in both directions: the effect is more modest, and the PN literature contains no reports of granuloma formation. That asymmetry is the main reason to reach for PN first in skin that is already thin, reactive, or has been through repeated energy-based treatment.

Six collagen boosters compared — which one fits →

Reasonable candidates

• Skin that has become thin and crepey without significant volume loss
• Periorbital skin, where volumising carries real risk
• Skin that has become reactive after repeated lasers or energy-based lifting
• Complaints centred on texture, dryness and makeup sitting poorly
• Acne scarring, where surface quality is the problem
• Patients who want to avoid particulate products because of nodule concerns

Where Rejuran alone will not get you there

• Hollowing of the cheeks or temples — PN provides no structural support. Filler or a volumising approach is required
• A softening jawline — this belongs to lifting devices or collagen stimulators
• Deep dynamic lines — botulinum toxin or filler
• A single-session solution — Rejuran is cumulative by design
• Pregnancy or breastfeeding, active infection at the treatment site, autoimmune disease, under 18

Very few patients fall cleanly on one side. Thinning skin and volume loss usually arrive together, and in that situation Rejuran on its own will underdeliver. Deciding which problem is dominant is most of what a consultation is for.

Setting this out honestly is part of the point of this page.

At the level of cell and animal work, the findings are reasonably consistent: fibroblast proliferation, increased type I and III collagen expression, reduced inflammatory cytokines.

Human clinical studies exist, but they are small. Most enrol tens of patients rather than hundreds, follow-up rarely exceeds six months, and outcomes are usually scored on subjective global-improvement scales. Standardised photography and instrumental measurement are uncommon. Reviews of the field converge on the same criticisms: heterogeneous protocols, small samples, and long-term efficacy and safety that remain uncertain.

The fair summary is this. The direction of effect on skin quality is consistent across studies; the magnitude is not something anyone can responsibly put a number on. Long-term safety data are likewise thin — and "no adverse events have been reported" is a different statement from "long-term safety has been established."

The consultation begins by separating the presenting problem into density or volume. If Rejuran is appropriate, formulation and treatment area are chosen from there.

Topical anaesthetic is applied for 20–30 minutes. The product is then placed into the dermis through a fine needle at many separate points, small volumes at roughly 3–5 mm intervals. With HB PLUS, the lidocaine diffuses as the session proceeds and later passes are usually more comfortable than the first.

Immediately afterwards, each injection point stands slightly proud of the skin. These blebs are simply product sitting in the dermis — a physical depot, not the foreign-body nodule associated with particulate stimulators — and they settle as the material is absorbed.

Miso Clinic works to a course of 3–4 sessions at 3–4 week intervals, which matches both the published protocols and the pattern reported by Korean aesthetic physicians in survey data. Scar work requires a longer programme.

Most patients return to normal activity the same day. Blebs may not be fully concealable under makeup for a day or two, so allow two or three days before anything important.

• Cleanse gently with lukewarm water on the day; do not rub the treated area
• Avoid sauna, jjimjilbang, strenuous exercise and alcohol for the first day
• Use sun protection diligently
• Resume makeup when your clinician advises
• A cold compress on the day helps if swelling concerns you

Few aesthetic treatments generate such divided accounts. The explanations we see in clinic fall into six groups.

1. The problem was never the one PN addresses

The most common. Shadowing from volume loss, or a contour that has descended, treated with a product that provides no structure. No quantity of PN corrects a structural complaint.

2. Too few sessions

Published protocols run to three or four. Single-session accounts are, unsurprisingly, the ones that dominate online reviews.

3. Judged too early

Improvement has been reported as clearer at twelve weeks than at two. Why onset is delayed is not well understood, and reviews list it as an open question.

4. The effect size is genuinely modest

In real-world data, around half of facial treatments were rated "much improved" or better — meaning the other half experienced something milder. Rejuran is not a dramatic treatment and should not be sold as one.

5. Expectations were never calibrated

Because the studies rest on subjective scales, there is no clean objective benchmark to expect. Standardised before-and-after photography under matched conditions is the practical remedy.

6. The formulation was wrong for the patient

People do abandon courses because of discomfort. Starting with a lidocaine-containing formulation makes finishing the course considerably more likely.

This reference was written and reviewed by Dr. Lee Chi-Hak, director of Miso Clinic in Daegu, South Korea. The clinic stocks six collagen boosters and skin boosters with genuinely different active materials — liquid PCL (GOURI), PN (Rejuran), hADM (Re2O, CellREDM) and CaHA (Radiesse, DCLASSY) — and selects between them according to which kind of ageing the face is actually showing. A clinic holding one product will use that product. Our comparison of all six explains how they differ, and there are separate references on liquid PCL and hADM.