Increasing i-PRF with vitamins A and C: a lever for periodontal regeneration?

The management of intra-osseous defects in patients with stage III periodontitis represents a major clinical challenge, requiring protocols that combine clot stability with enhanced regenerative potential. While the modified minimally invasive surgical technique (M-MIST) has already proven effective in limiting morbidity, the biological optimization of the filling remains a current issue. This study specifically addresses this lever by utilizing injectable platelet-rich fibrin (i-PRF) not only as a platelet concentrate, but as a sustained-release vector for synergistic biomolecules: vitamins A and C.

The objective of this triple-blind randomized controlled trial was to compare the clinical and radiographic efficacy of i-PRF enriched with vitamins A and C (VitA+C/i-PRF) versus conventional i-PRF, both combined with the M-MIST technique. Conducted on 28 patients with stage III grade B periodontology, this study evaluates whether the incorporation of these vitamins at concentrations inducing cellular pluripotency significantly improves bone defect healing at 6 and 9 months.

The central hypothesis is based on the synergistic effect of vitamins A and C on cellular regenerative capacities. The authors test whether this combination, delivered in situ via the release kinetics of i-PRF, achieves superior clinical attachment gain (CAL), a more marked reduction in probing depth (PD), and better radiographic bone fill (RBF) compared to the use of i-PRF alone.

Methodology: a triple-blind clinical trial

This parallel-group randomized controlled trial (RCT) included 28 patients diagnosed with stage III, grade B periodontology. The study compared the efficacy of the M-MIST (Modified Minimally Invasive Surgical Technique) surgical technique combined with two different regeneration protocols.

The cohort was randomly divided into two groups:

• Test Group (n=14): Treatment with M-MIST combined with injectable platelet-rich fibrin (i-PRF) augmented by a combination of vitamins A and C (VitA+C).
• Control Group (n=14): Treatment with M-MIST combined with i-PRF alone.

In parallel, an in vitro phase characterized the release kinetics of vitamins A and C from the i-PRF matrix over a 7-day period, using high-performance liquid chromatography (HPLC). Clinically, parameters were recorded at baseline, then at 3, 6, and 9 months. The primary endpoint was the change in radiographic linear defect depth (RLDD). Secondary measures included clinical attachment level (CAL), probing depth (PD), gingival recession (GML), as well as radiographic bone fill (RBF) percentage and radiographic bone density (RBD), evaluated at 6 and 9 months.

Superior clinical and radiographic gains with the VitA+C combo

This triple-blind randomized study, conducted on 28 patients (n=14 per group) suffering from stage III grade B periodontology, demonstrates that the addition of vitamins A and C to i-PRF outperforms the use of i-PRF alone in the treatment of intra-osseous defects using the M-MIST technique.

Radiographic analysis: accelerated bone regeneration

The primary endpoint, the reduction in radiographic linear defect depth (RLDD), showed a significantly more marked improvement in the test group as early as 6 months (p < 0.05). This superiority is confirmed by the radiographic bone fill (RBF) percentage.

Radiographic Parameter	6-month results	9-month results
RLDD Reduction	Significant superiority of the VitA+C group (p < 0.05)	Improvement maintained in both groups
Bone filling (RBF %)	Significantly higher (VitA+C group)	Significantly higher (VitA+C group)
Relative Bone Density (RBD)	No significant intergroup difference	No significant intergroup difference

Clinical parameters: a marked benefit at 9 months

While both groups showed significant improvements over time for all parameters (CAL, PD, GML, RLDD), the group receiving vitamin-enriched i-PRF reached an additional milestone by the end of the follow-up. In the dental practice, this translates into better long-term periodontal stability.

• Clinical Attachment Gain (CAL): Significantly higher in the VitA+C group at 9 months (p < 0.05).
• Probing depth (PD) reduction: Statistical superiority of the test group at 9 months (p < 0.05).
• Tissue stability: Plaque (PI) and gingival (GI) indices were monitored, confirming overall tissue health with no reported adverse effects.

In vitro release kinetics

High-performance liquid chromatography (HPLC) analysis characterized the release kinetics of biomolecules over 7 days. i-PRF acts as a sustained-release vector, allowing vitamins A and C to maintain concentrations capable of inducing cellular pluripotency at the core of the bone defect during the critical healing phase.

Clinical analysis: the synergistic effect of vitamins A and C

The results of this triple-blind randomized trial conducted on 28 patients (n=14 per group) highlight the strategic interest of transforming i-PRF into a sustained-release vector. By supplementing i-PRF with a specific cocktail of vitamins A and C (VitA+C), the authors observed a reduction in radiographic lesion depth (RLDD) and a significantly higher radiographic bone fill (RBF) rate at 6 months compared to i-PRF used alone. This superiority is maintained at 9 months, confirming the positive impact of this combination on regeneration kinetics.

Why this difference? HPLC analysis shows that i-PRF ensures a sustained release of vitamins over 7 days. Clinically, this prolonged presence in the site treated by the M-MIST technique seems to stimulate local cellular pluripotency. Clinical attachment gain (CAL) and pocket depth (PD) reduction are thus more pronounced in the test group at the end of the 9-month follow-up. Notably, no intergroup difference was observed regarding bone density (RBD), suggesting that the vitamin effect relates more to the filling volume and soft tissue stability than to short-term intrinsic mineralization.

The study nevertheless presents limitations, notably a restricted sample size and an exclusive focus on stage III grade B periodontitis. While the M-MIST technique is already recognized for limiting morbidity and ensuring clot stability, the addition of VitA+C represents here a simple and cost-effective biological optimization. The data confirm that i-PRF alone improves parameters compared to baseline, but that the vitamin synergy allows for achieving statistically superior clinical and radiographic results.

Summary of results

This randomized clinical trial conducted on 28 patients (stage III, grade B) demonstrates that the addition of vitamins A and C to i-PRF outperforms i-PRF alone during an M-MIST procedure. At 9 months, the test group shows significantly superior clinical attachment gain (CAL) and pocket depth (PD) reduction, as well as greater radiographic bone fill (RBF), validating i-PRF as an effective sustained-release carrier over 7 days.

In concrete terms, for the practitioner:

• Optimize your regeneration protocols: Enriching i-PRF with vitamins A and C constitutes a simple lever to improve clinical and radiographic parameters of deep intrabony defects.
• Opt for the M-MIST / Biomolecules combo: The minimally invasive surgical technique (M-MIST) ensures clot stability, while the VitA+C/i-PRF complex boosts local cellular pluripotency.
• Harness release kinetics: Use i-PRF as a biological carrier to maintain a therapeutic concentration of essential nutrients directly at the surgical site during the critical healing phase.

The use of platelet-rich fibrin (PRF) as a sustained-release carrier opens new perspectives in periodontal regeneration. This recent triple-blind randomized clinical trial evaluated the impact of an i-PRF "augmented" by a combination of vitamins A and C (VitA+C) in the treatment of intrabony defects.

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