Miso Clinic · Clinical column

Re2O in Daegu — needle or cannula: what is known and what is not yet

Re2O (acellular human dermal matrix, hADM) is the same product everywhere, yet clinics deliver it differently: a fine needle with many small passes, a blunt cannula threaded under the skin, or an automatic injector. So in consultations we are often asked, “Which one works better?” This page separates what published data can answer from what, honestly, it cannot answer yet.

Clinical column About 5 min October 2026 Miso Clinic, Daegu · Dr. Lee Chi-Hak, Medical Director

The short answer

We found no human study that compares needle and cannula for Re2O itself (PubMed and ClinicalTrials.gov, searched 9 October 2026). There is only one randomized human trial of Re2O, and it used a single method: intradermal injection. With other injectables (mostly hyaluronic acid fillers), efficacy was usually similar, and the differences showed up in pain, bruising and the plane where the product ends up. Because the injection plane and the product are different, those results cannot simply be carried over to Re2O. At Miso Clinic, Daegu (4F Bombom Building, 125 Dongdeok-ro, Jung-gu, Daegu; +82-53-428-2700) we do not fix one tool in advance; we choose between cannula and needle after checking the goal, area, schedule and pain tolerance with each patient.

What has been confirmed for Re2O

The randomized human trial of Re2O followed 20 people for 20 weeks. One side of the face received Re2O and the other hyaluronic acid, and neither the injector nor the patient knew which side was which. The registry entry lists three sessions one month apart, injected into the dermis.

So the efficacy data we have for Re2O describe what happens “when it is placed in the dermis, that way”. Whether a cannula gives the same result is not a question this trial answers.

We also could not confirm the amount used per session in the paper, the registry or the manufacturer’s public material, as noted in our Re2O consultation column. In August 2026 the manufacturer announced an advisory board to set injection sites, ranges and standard use. Put the other way round, a standard injection method is still being worked out.

Other injectables: efficacy was mostly the same

Without Re2O data, we looked at trials of other injectables that compared needle and cannula head to head.

  • Cheek volume (hyaluronic acid, 60 people, randomized by cheek): one-month improvement −1.8 with cannula, −1.9 with needle. The cannula was non-inferior.
  • Nasolabial folds (hyaluronic acid, 50 people, split-face): the cannula was non-inferior.
  • Under-eye (hyaluronic acid, 42 people): no difference in efficacy, safety or satisfaction.
  • Under-eye (hyaluronic acid, 333 people): 3-month responder rates were essentially identical (P=0.967).

There was one exception. For horizontal neck lines (20 people, one side each), evaluators, patients and injectors all judged the needle side as more improved. I read that as a sign that the tool can change the result when the target is shallow lines.

A 15-person case series of a skin booster compared serial needle, cannula and a multi-needle injector. Firmness and hydration changes were similar, and mean pain was 2.2 with the cannula and 4.6 with the needle. It was not randomized.

Pain, bruising and vascular problems

In a 25-person nasolabial study, pain, swelling, redness and bruising were all lower on the cannula side. Yet in the 333-person under-eye trial above, adverse events were reported by 4.9% with the needle and 20.9% with the cannula, the opposite direction. The claim “cannulas don’t bruise” does not hold up.

Vascular occlusion was rare with both and rarer with cannulas. In an analysis of about 1.7 million syringes reported by 370 dermatologists, it occurred in 1 per 6,410 syringes with a needle and 1 per 40,882 with a cannula. That was a retrospective survey of fillers.

On placement, the answer depends on how you define “accurate”. In a cadaver study, 60% of needle injections left the intended plane versus 0% with the cannula; the cannula, however, spread wider (25.6 vs 13.5 mm) and more often flowed back toward the entry point.

Why these results cannot be applied directly to Re2O

  1. The injection plane differs. Most trials above placed volumizing fillers subcutaneously or on the periosteum. The Re2O trial injected into the dermis. A cannula usually glides beneath the skin, so whether a product meant to stay in the dermis behaves the same way needs its own evidence.
  2. The product differs. Re2O is not a hyaluronic acid gel but particles of processed human dermis. I could not find human measurements of how those particles spread or stay depending on the tool.
  3. The dose is not public. Without knowing whether the same amount went into the same area, there is no fair basis for comparing the two methods.

What to check when you see “satisfaction of a few dozen patients”

Collected satisfaction data from patients who had each method is a reasonable starting point. To draw a conclusion, though, check these points.

  • Were needle and cannula assigned at random, or chosen by the injector based on each patient?
  • Were both sides of the same face compared, or different people?
  • Was the evaluator unaware of which method was used?
  • Did the questionnaire offer a neutral middle option such as “about the same”? One study saw satisfaction for the same treatment change from 84% to 62% depending on this (see our natural lifting column).

A comparison without these four is hard to use as evidence that one method works better.

What we decide together in consultation

Since the published evidence cannot rank the tools, the choice comes down to the goal and what you are willing to accept, not an efficacy ranking.

  • What you want to change — shallow changes such as texture and fine lines, or even treatment of a wider area
  • Where — thin-skinned areas such as under the eyes or the neck
  • Schedule — an important event within days, where limiting bruising and swelling comes first
  • Pain — how much you can tolerate, together with the anesthesia method

We do not perform Re2O with a single fixed tool. After going through these four points, we choose cannula or needle (hand injection) according to what each patient needs. Not because one works better, but because goals, areas and schedules differ from person to person.

What we could not confirm

  • A human study comparing needle and cannula for Re2O (hADM)
  • A primary source for the Re2O dose per session
  • A study measuring how much particulate hADM remains in the dermis depending on the tool
  • The injection standard the manufacturer’s advisory board will publish (no public document as of October 2026)
  • A study comparing an automatic injector with hand injection for Re2O

Re2O needle vs cannula: frequently asked questions

Is Re2O more effective with a cannula or a needle?

We found no human study comparing the two for Re2O. With other injectables (mostly hyaluronic acid fillers) efficacy was usually similar, and one trial on shallow neck lines favored the needle.

Does a cannula hurt less and bruise less?

Many studies found less pain and bruising with a cannula. But in a 333-person under-eye trial, adverse events were reported by 4.9% with the needle and 20.9% with the cannula. It cannot be said that cannulas do not bruise.

How was Re2O injected in its clinical trial?

The one randomized human trial (20 people, 20 weeks, split-face) used three intradermal sessions one month apart. It has no data on cannula delivery.

Which carries the lower risk of vascular occlusion?

In a survey of about 1.7 million filler syringes, it was 1 per 6,410 syringes with a needle and 1 per 40,882 with a cannula. Both are rare, and these are filler data, so we do not transfer them directly to Re2O.

Which tool does Miso Clinic use for Re2O?

We do not fix one in advance. We check what you want to change, the area, your schedule and pain tolerance, then choose cannula or needle (hand injection).

What is the Re2O dose per session?

We could not confirm a primary source for the dose per session in the paper, the registry or the manufacturer’s public material, so we do not state a number.

Can I trust satisfaction comparison videos?

They are a reasonable starting point. Without random assignment, same-person comparison, blinded evaluation and a neutral answer option, they are weak evidence of which method works better.

Read next

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Who wrote this

Written and reviewed by Lee Chi-Hak, MD, director of Miso Clinic, Daegu. The treatment standards and injection design set out here are the ones we use in practice.

Miso Clinic
Medical directorLee Chi-Hak, MD
Address4F Bombom Building, 125 Dongdeok-ro, Jung-gu, Daegu, South Korea · Exit 1, Kyungpook National University Hospital Station
Phone+82-53-428-2700
HoursWeekdays 11:00–19:00 (lunch 13:00–14:00) / Saturday 10:00–16:00 (no lunch break) / Closed Sundays and public holidays
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Reference libraryAll booster and device references

References

  1. Randomized human trial of Re2O — Lee YI et al., Int J Mol Sci 2026;27(5):2193, DOI 10.3390/ijms27052193. 20 participants · 20 weeks · split-face (Re2O on one side, hyaluronic acid on the other) · injector and patient blinded.
  2. Registry — ClinicalTrials.gov NCT07155278 (Yonsei University, started November 2024 · completed May 2025). Three sessions one month apart, intradermal injection.
  3. Cheek volume, needle vs cannula — Jones D et al., Dermatol Surg 2021;47(12):1590–1594, DOI 10.1097/DSS.0000000000003246. Hyaluronic acid, 60 participants, randomized by cheek. One-month improvement −1.8 (cannula) vs −1.9 (needle); cannula non-inferior.
  4. Nasolabial folds, needle vs cannula — Beer K et al., Clin Cosmet Investig Dermatol 2023;16:959–972, DOI 10.2147/CCID.S402315. Hyaluronic acid, 50 participants, split-face; cannula non-inferior.
  5. Under-eye, needle vs cannula (42 participants) — Nikolis A et al., Aesthet Surg J 2022;42(3):285–297, DOI 10.1093/asj/sjab284. No between-group difference in efficacy, safety or satisfaction.
  6. Under-eye, needle vs cannula (333 participants) — Biesman BS et al., Aesthet Surg J 2024;44(9):1001–1013, DOI 10.1093/asj/sjae073. No difference in 3-month responder rate (P=0.967). Adverse events reported by 4.9% (needle) vs 20.9% (cannula).
  7. Horizontal neck lines, needle vs cannula — Siperstein R et al., Dermatol Surg 2022;48(4):423–428, DOI 10.1097/DSS.0000000000003391. Hyaluronic acid, 20 participants, one side of the neck each. Evaluators, patients and injectors all rated the needle side as more improved.
  8. Skin booster delivery case series — Booysen K, Lin F. J Cosmet Dermatol 2026;25(1):e70660, DOI 10.1111/jocd.70660. Hyaluronic acid + glycerol, 15 participants; serial needle, cannula, multi-needle injector. Similar results; pain 2.2 (cannula) vs 4.6 (needle). Not randomized.
  9. Pain and bruising, nasolabial folds — Hexsel D et al., Dermatol Surg 2012;38(2):207–214, DOI 10.1111/j.1524-4725.2011.02195.x. 25 participants; less pain, swelling, redness and bruising on the cannula side.
  10. Frequency of vascular occlusion — Alam M et al., JAMA Dermatol 2021;157(2):174–180, DOI 10.1001/jamadermatol.2020.5102. Retrospective survey of 370 dermatologists, about 1.7 million syringes. Needle 1 per 6,410 syringes, cannula 1 per 40,882 syringes. Fillers only.
  11. Placement depth (cadaver) — Pavicic T et al., J Drugs Dermatol 2017;16(9):866–872. Off-target plane 60% (needle) vs 0% (cannula), but spread 25.6 vs 13.5 mm and reflux 90.2% vs 33.3%.
  12. Narrative review — Lee KWA et al., JPRAS Open 2025;48:415–424, DOI 10.1016/j.jpra.2025.12.002.
  13. Manufacturer advisory board — Dailypharm (Korean trade press), 24 August 2026: L&C Bio launched a Re2O advisory board to define indications, injection sites and ranges, and standard use. No public document as of October 2026.

Everything in this column is general information and does not replace medical diagnosis or treatment. Effects and side effects vary with individual skin condition, age and underlying illness, and the same result is not guaranteed for everyone. Any decision to proceed should be made in an in-person consultation with a physician.

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