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PDRN Microneedling Treatment Protocol

A clinical protocol for combining PDRN with microneedling to enhance collagen induction therapy. Covers device selection, needle depth, PDRN application timing, and post-treatment care.

Dr. Min-Ji Park

Dr. Min-Ji Park

MD, Board-Certified Dermatologist

7 minSeptember 1, 2025Updated March 25, 2026

Overview

This protocol describes the combination of microneedling (percutaneous collagen induction therapy) with PDRN application to enhance skin rejuvenation outcomes [1][4]. Microneedling creates controlled micro-injuries in the skin, triggering the wound healing cascade and opening transient microchannels that allow topically applied PDRN to penetrate directly to the dermal level [4]. This combination leverages two complementary mechanisms: the collagen induction response from microneedling and the A2A receptor-mediated regeneration from PDRN [2][5].

Rationale

Microneedling alone stimulates collagen through the wound healing response [4]. Adding PDRN amplifies this response in several ways [2][3]:

  • Enhanced fibroblast activation — PDRN directly stimulates the fibroblasts recruited by the microneedling wound response [2][3]
  • Improved angiogenesis — PDRN upregulates VEGF, enhancing blood supply to the treated tissue and improving healing quality [5]
  • Anti-inflammatory modulation — PDRN's A2A receptor activation helps manage post-needling inflammation, reducing downtime [2]
  • Nucleotide supply — PDRN provides building blocks for the DNA synthesis required by rapidly proliferating cells during healing [2][3]

Patient Selection

Indications

  • Mild to moderate photoaging (fine lines, uneven texture, loss of elasticity) [1][4]
  • Acne scarring (rolling and boxcar types) [4]
  • Post-inflammatory hyperpigmentation [3]
  • Skin dullness and dehydration [1][6]
  • Enlarged pores [4]

Contraindications

  • Active acne or skin infection at treatment site [4]
  • Active herpes simplex — prescribe antiviral prophylaxis if history present
  • Known hypersensitivity to fish-derived products
  • Pregnancy or breastfeeding
  • Keloid tendency (relative — use conservative needle depth)
  • Current isotretinoin use or within 6 months of discontinuation [4]
  • Anticoagulant therapy (relative — assess bleeding risk)

Pre-Treatment Preparation

  1. Consultation — Assess skin condition, review medical history, discuss realistic expectations, obtain informed consent, and capture baseline photographs under standardized lighting [1][4].
  2. Skin preparation (2 weeks prior) — Discontinue retinoids, AHAs, and BHAs 5-7 days before treatment. Consider pre-treatment with a gentle PDRN serum to prime fibroblasts [3].
  3. Day of treatment — Cleanse the face thoroughly with a gentle antiseptic (chlorhexidine 0.05%). Remove all makeup, sunscreen, and skincare products.
  4. Anesthesia — Apply topical anesthetic cream (lidocaine 2.5%/prilocaine 2.5%) under occlusion for 20-30 minutes. Remove and re-cleanse completely before treatment [4].

Equipment

  • Motorized microneedling pen (recommended) or manual derma roller [4]
  • Sterile needle cartridges: 12-pin or 36-pin (pen) or 0.5-1.5 mm (roller)
  • PDRN serum or solution (topical-grade for application during needling)
  • Injectable PDRN skin booster (optional, for post-needling intradermal injection)
  • Sterile gauze and soothing post-treatment mask

Treatment Technique

Step 1: First PDRN application

Apply a generous layer of PDRN serum to the cleansed, anesthetized face immediately before microneedling [3]. This ensures PDRN is available to enter the microchannels as they are created.

Step 2: Microneedling

Perform microneedling systematically across the face, zone by zone [4]:

ZoneNeedle DepthPassesNotes
Forehead0.5-1.0 mm3-4Avoid brow ridge
Cheeks1.0-1.5 mm4-6Deepest treatment zone
Nose0.5 mm2-3Gentle pressure
Periorbital0.25-0.5 mm2-3Very light pressure, shorter needle
Perioral0.5-1.0 mm3-4Follow natural lines
Jawline/chin1.0-1.5 mm3-4Standard depth

Technique notes:

  • Maintain consistent speed and pressure across each zone [4]
  • Move the device in vertical, horizontal, and diagonal passes for uniform coverage [4]
  • Re-apply PDRN serum between zones as needed to keep the skin moist and ensure continued ingredient delivery [3]
  • Target endpoint: uniform pinpoint bleeding and mild erythema across all treated zones [4]

Step 3: Final PDRN application

After completing microneedling, apply a final layer of PDRN serum to the entire face while microchannels remain open (within 5-10 minutes of needling) [3]. Gently press the serum into the skin using light patting motions — do not rub or drag.

Step 4 (Optional): PDRN intradermal injection

For enhanced results, follow microneedling with targeted PDRN skin booster injections using the nappage technique in areas of greatest concern (periorbital, nasolabial, cheeks) [1][6]. Use a 32G needle, 0.01-0.02 mL per point, spaced 5-10 mm apart.

Step 5: Post-treatment mask

Apply a soothing hydrogel or bio-cellulose mask for 15-20 minutes to calm the skin and deliver additional hydration [1].

Treatment Schedule

PhaseSessionsIntervalPurpose
Induction3-4 sessionsEvery 3-4 weeksBuild collagen response and tissue remodeling [1][4]
Maintenance1 sessionEvery 2-3 monthsSustain and extend results [1]

Allow a minimum of 3 weeks between sessions to ensure complete healing and collagen maturation before re-treating [4].

Post-Treatment Care

Immediate (first 24 hours)

  • Apply prescribed PDRN serum or recovery serum only — no other actives [3]
  • Avoid touching the face, applying makeup, or swimming
  • Mild to moderate erythema, tightness, and sensitivity are expected and typically resolve within 24-48 hours [4]
  • Avoid vigorous exercise, saunas, and hot showers

Days 2-7

  • Continue PDRN serum application twice daily [3]
  • Use gentle cleanser and moisturizer only
  • Avoid retinoids, AHAs, BHAs, vitamin C, and other active ingredients
  • Apply broad-spectrum SPF 50+ sunscreen every morning — mandatory [1][4]
  • Mild flaking or dryness may occur around days 3-5 — moisturize generously but do not pick or exfoliate

Week 2 onward

  • Resume normal skincare routine gradually [4]
  • Continue daily PDRN serum for ongoing support between treatment sessions [3]
  • Maintain consistent sun protection

Expected Outcomes

Results are progressive and cumulative over the treatment course [1][4]:

  • Week 1-2 — Improved hydration, subtle glow, smoother texture as initial inflammation resolves [1]
  • Week 4-8 — Visible improvement in fine lines, skin elasticity, and overall skin quality as new collagen is deposited [1][4]
  • Week 8-16 — Peak collagen remodeling with maximum improvement in firmness, pore size reduction, and scar improvement [4]
  • Ongoing — Results maintained and extended with maintenance sessions and daily PDRN serum use [1][3]

Clinical studies and clinical experience suggest that the combination of microneedling with PDRN produces superior results compared to either treatment alone, with faster recovery and less downtime than microneedling without PDRN [1][2][5].

Reviewed by Dr. Sarah Chen, PhD, Molecular Biology

References

  1. [1]
    Kim TH, Kim JH, Lee SH, Park ES. Biostimulatory effects of polydeoxyribonucleotide for facial skin rejuvenation. Journal of Cosmetic Dermatology. 2019;18(6):1767-1773. doi:10.1111/jocd.12958
  2. [2]
    Squadrito F, Bitto A, Irrera N, et al.. Pharmacological Activity and Clinical Use of PDRN. Current Pharmaceutical Design. 2017;23(27):3948-3957.
  3. [3]
    Colangelo MT, Galli C, Gentile P. Polydeoxyribonucleotide: A Promising Biological Platform for Dermal Regeneration. Current Pharmaceutical Design. 2020;26(17):2049-2056.
  4. [4]
    Aust MC, Fernandes D, Kolokythas P, Kaplan HM, Vogt PM. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity. Plastic and Reconstructive Surgery. 2008;121(4):1421-1429. doi:10.1097/01.prs.0000304612.57234.2f
  5. [5]
    Galeano M, Bitto A, Altavilla D, et al.. Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair and Regeneration. 2008;16(2):208-217. doi:10.1111/j.1524-475X.2008.00361.x
  6. [6]
    Cavallini M, Papagni M, Trocchi G. Hyaluronic acid and polynucleotides combination for skin bio-revitalization. Dermatologic Therapy. 2021;34(1):e14572. doi:10.1111/dth.14572
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