Comparative Evaluation of Injectable Platelet-Rich Fibrin with and Without Microneedling in Periodontal Regeneration: A Prospective Split-Mouth Clinical Study

<b>Background/Objectives:</b> Periodontal disease is a prevalent chronic inflammatory condition that often progresses to irreversible tissue destruction. This study aimed to evaluate the clinical efficacy of a combined minimally invasive periodontal therapeutic protocol scaling and root planing (SRP) with injectable platelet-rich fibrin (i-PRF) and microneedling (MN) compared to conventional SRP with i-PRF alone in patients with stage II-III periodontitis. <b>Methods:</b> A prospective split-mouth clinical study was conducted on 54 patients diagnosed according to the 2018 EFP/AAP classification. Each participant received SRP + i-PRF in the upper arch (control) and SRP + i-PRF + MN in the lower arch (test). Periodontal parameters clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) were measured at baseline, 1, 3, and 6 months. Data were analyzed using Friedman and Wilcoxon tests with Bonferroni correction. <b>Results:</b> Both treatment protocols produced significant longitudinal improvements in CAL, BOP, and PI (<i>p</i> < 0.001). The most pronounced BOP reduction occurred within the first month, while CAL improvement was progressive and stabilized after six months. The Combined protocol achieved slightly greater CAL gain at 6 months (mean difference ≈ 0.46 mm; <i>p</i> = 0.0013), indicating a modest yet statistically significant advantage in attachment recovery. Correlation analyses confirmed a coherent healing trajectory characterized by early inflammation resolution, plaque control, and later tissue stabilization. <b>Conclusions:</b> Both i-PRF-based regenerative approaches significantly improved periodontal parameters. The addition of MN enhanced CAL recovery and may favor early vascularization and collagen remodeling. Although the clinical difference was limited, the biological plausibility and sustained improvement suggest that MN could represent a valuable adjunct to non-surgical regenerative periodontal therapy. Longer-term studies are warranted to assess the durability of these effects.