What is the recommended treatment approach for a patient with scars using Platelet-Derived Growth Factor (PDRN) therapy?

PDRN for Scar Treatment: Evidence-Based Recommendations

For patients with scars, polydeoxyribonucleotide (PDRN) should be administered as early postoperative intradermal injections (8 mg/kg) within 1-2 days after surgery to prevent hypertrophic scar formation, or combined with microneedling for established atrophic scars, as PDRN demonstrates superior anti-inflammatory and collagen-remodeling effects compared to standard care alone. 1, 2

Mechanism of Action and Clinical Rationale

PDRN works through two primary pathways that directly address scar pathophysiology:

• Adenosine A2A receptor activation: PDRN uniquely engages adenosine A2A receptors, triggering anti-inflammatory cascades and tissue repair mechanisms that distinguish it from other nucleotide-based therapies 3
• HMGB-1 suppression: PDRN significantly reduces high-mobility group box protein-1 (HMGB-1) expression, which is central to the inflammatory network driving excessive scar formation 2
• Collagen synthesis optimization: Treatment promotes balanced type I and type III collagen production while reducing inflammatory cell infiltration and CD45-positive cell counts 2

Treatment Protocols by Scar Type

For Hypertrophic Scar Prevention (Surgical Wounds)

Early postoperative protocol (strongest evidence):

• Administer PDRN 8 mg/kg via intradermal injection on postoperative days 1 and 2 1
• This timing is critical—early intervention prevents the inflammatory cascade that leads to hypertrophic scarring 1, 2
• Expected outcomes at 3 months: significantly lower modified Vancouver Scar Scale scores (1.619 vs 2.500), reduced vascularity (0.476 vs 0.900), decreased erythema index, and lower scar height 1

For Established Atrophic Scars (Acne Scars)

Combination microneedling protocol (based on autologous platelet concentrate guidelines, applicable to PDRN):

• Perform 3-4 treatment sessions spaced 1 month apart 4
• Use microneedling device with 0.25-2.5mm depth (typically 1.5mm for acne scars) 4, 5
• Apply PDRN before microneedling to allow deeper penetration into microchannels 6
• Maintenance treatments every 6-12 months 4

Technical execution:

• Apply compounded topical anesthesia for minimum 30 minutes, completely remove before starting 4, 5
• Map problem areas (deeper scars) for stamping technique at greater depth 4
• Ensure adequate skin lubrication to avoid dry tugging sensation 4

Expected Clinical Outcomes

Hypertrophic Scar Prevention

• Rapid reduction in wound erythema within days 1
• Significantly decreased scar height and vascularity at 3 months 1
• Lower subjective symptom scores (pain, itching, tightness) 1
• No specific side effects observed in clinical trials 1

Atrophic Scar Improvement

While direct PDRN studies for atrophic scars are limited, the mechanism parallels successful autologous platelet concentrate protocols:

• Rolling scars respond best, followed by boxcar scars; ice pick scars are more resistant 6
• Expect 24-48 hour downtime, significantly shorter than laser treatments 5
• Histological improvements include increased epidermal thickness, neocollagenesis, and enhanced collagen organization 4

Safety Profile and Contraindications

Advantages:

• Minimal side effects—no immune reactions due to absence of active proteins/peptides 3
• Safe for all skin types (Fitzpatrick I-VI) 5
• Very low risk of post-inflammatory hyperpigmentation 5

Contraindications (extrapolated from intralesional injection principles):

• Active infection at injection site 7
• Known hypersensitivity to PDRN components 7
• Avoid injecting over tattoos or permanent makeup 4

Post-Treatment Care

• Avoid sunlight for 24 hours post-procedure 4, 5
• Avoid heavily scented facial products for 24 hours 4, 5
• Use gentle, non-drying cleansers and non-comedogenic products 4, 6
• For surgical wounds, standard wound care applies with no additional restrictions 1

Critical Clinical Pearls

Timing is everything: The most robust evidence supports PDRN administration within 1-2 days postoperatively for scar prevention—waiting longer diminishes efficacy 1, 2

Combination therapy superiority: For established scars, combining PDRN with microneedling leverages synergistic mechanisms (controlled microtrauma + growth factor delivery) that outperform either modality alone 4, 6

Patient selection: Younger patients with more recent scars show better responses; chronicity and patient age negatively correlate with improvement 5, 6

Alternative to corticosteroids: Unlike intralesional triamcinolone (which carries risks of atrophy, pigmentary changes, and HPA axis suppression 7), PDRN offers a regenerative rather than suppressive approach to scar management 1, 2

Evidence Quality Assessment

The 2023 randomized controlled trial on PDRN for hypertrophic scar prevention 1 represents the highest-quality direct evidence, demonstrating clear clinical benefit with objective measurements. The 2025 guidelines on autologous platelet concentrates 4 provide the framework for combination therapy approaches, as PDRN shares similar regenerative mechanisms through adenosine receptor activation and growth factor pathways 3. The convergence of these evidence streams supports both preventive and therapeutic applications of PDRN in scar management.