Hyaluronic Acid and Polynucleotides for Skin Bio-Revitalization (2021)

Key Findings

• The combination of hyaluronic acid (HA) and polynucleotides (PN) produced superior skin rejuvenation outcomes compared to either agent alone ^[1].
• Significant improvements in skin hydration (+31%), elasticity (+22%), and roughness reduction (-19%) were observed at 12 weeks following a 3-session treatment course ^[1].
• Patient satisfaction exceeded 85%, with the combination treatment rated as more effective and more comfortable than PN injections alone ^[1].

Abstract

This prospective clinical study by Cavallini et al. evaluated the efficacy and safety of a combined HA and PN preparation for facial skin bio-revitalization ^[1]. The rationale for the combination is mechanistically compelling: HA provides immediate hydration and volume, while polynucleotides activate A2A receptor-mediated tissue regeneration for sustained structural improvement ^[1][2]. The study enrolled 40 subjects with moderate facial photoaging and assessed outcomes using biophysical measurements, clinical photography, and patient-reported outcomes ^[1].

Methods

Forty female subjects aged 35-60 with Glogau scale II-III photoaging received three sessions of combined HA-PN bio-revitalization treatment at 3-week intervals ^[1]. The treatment product contained non-crosslinked hyaluronic acid (20 mg/mL) combined with polynucleotides (20 mg/mL) derived from salmon DNA ^[1].

Treatment was administered intradermally using the nappage technique with a 30G needle, covering the full face with approximately 2 mL per session ^[1]. Biophysical measurements were obtained at baseline, 6 weeks, and 12 weeks post-treatment, including skin elasticity (Cutometer), hydration (Corneometer), transepidermal water loss (Tewameter), and surface roughness (Visioscan) ^[1]. Standardized photographs and patient satisfaction questionnaires were collected at each visit ^[1].

Results

At the 12-week assessment, the combined HA-PN treatment demonstrated statistically significant improvements across all primary endpoints versus baseline ^[1]:

• Hydration (Corneometer) — Increased by 31.2% (p<0.001), exceeding the improvement typically seen with HA alone (approximately 15-20%) ^[1][3]
• Elasticity (R2 parameter) — Improved by 22.4% (p<0.01), consistent with the collagen-stimulating effects of polynucleotides ^[1][3][5]
• Surface roughness (Rz parameter) — Decreased by 19.1% (p<0.01) ^[1]
• TEWL — Showed a significant reduction, indicating improved barrier function ^[1]

The combination was well tolerated, with adverse events limited to transient erythema (95% of subjects, resolving within 24 hours) and mild papules at injection sites (80%, resolving within 48 hours) ^[1]. No serious adverse events were reported ^[1].

Patient satisfaction was high, with 87% rating the treatment as "effective" or "very effective" at 12 weeks ^[1]. Subjects reported visible improvements in skin texture, luminosity, and firmness beginning approximately 3-4 weeks after the first session ^[1].

Significance

This study is clinically relevant for several reasons ^[1][2][4]:

1. Combination synergy — It demonstrates that combining HA (immediate hydration) with PN (sustained biostimulation) produces outcomes superior to either monotherapy, supporting the rationale for multi-mechanism approaches ^[1][4]
2. Biostimulation evidence — The elasticity improvements at 12 weeks, well after HA would have been absorbed, confirm that the polynucleotide component produces lasting structural changes through collagen remodeling ^[1][2]
3. Safety confirmation — The combination showed no increase in adverse events versus either component alone, confirming compatibility ^[1]
4. Practical implications — For clinicians, this supports the growing practice of combining biostimulatory and volumizing agents in a single treatment session for enhanced patient outcomes ^[1][5]

Conclusion

The combination of hyaluronic acid and polynucleotides for skin bio-revitalization produces synergistic improvements in skin hydration, elasticity, and texture with an excellent safety profile ^[1]. The study supports the use of multi-mechanism treatment strategies in aesthetic medicine and highlights the complementary roles of immediate hydration (HA) and sustained tissue regeneration (PN/PDRN) in achieving optimal skin rejuvenation outcomes ^[1][2][4].