Background and Objectives: This study aimed to evaluate the effects of advanced platelet-rich fibrin (A-PRF+) tissue regeneration therapy on clinical periodontal parameters in non-smokers and smoker patients. The anticipated biological mechanisms of A-PRF+ include stimulating angiogenesis, thereby promoting the formation of new blood vessels, which is essential for tissue healing. Additionally, A-PRF+ harnesses the regenerative properties of platelet-rich fibrin, contributing to the repair and regeneration of periodontal tissues. Materials and Methods: The study was conducted on 55 patients, divided into two groups: non-smoker patients (n = 29) and smoker patients (n = 26). A single operator conducted the surgical procedure. Following the administration of local anesthesia with articaine 4% with adrenaline 1:100,000 precise intracrevicular incisions were made, extending towards the adjacent teeth, until the interproximal spaces, with meticulous attention to conserving the interdental gingival tissue to the greatest extent possible. Extended, full-thickness vestibular and oral flaps were carefully lifted, and all granulation tissue was meticulously removed from the defect without altering the bone contour. After debridement of the defects, A-PRF+ was applied. BOP (bleeding on probing), PI (plaque index), CAL (clinical attachment loss), and probing depth (PD) were determined at baseline and six months post-surgery. Results: Significant reductions were observed in PD and CAL after six months. In the non-smokers group, PD decreased from 7.0 ± 1.0 mm to 3.1 ± 0.1 mm (p < 0.001), while in the smokers group, PD decreased from 6.9 ± 1.1 mm to 3.9 ± 0.3 mm (p < 0.001). CAL decreased in the non-smokers group from 5.8 ± 0.7 mm to 2.6 ± 0.2 mm and from 5.7 ± 0.9 mm to 3.2 ± 0.2 mm (p < 0.001) in smokers. Notably, the reductions in CAL and PD were statistically more significant in the non-smokers group. Conclusions: Even though the clinical periodontal improvements were considerable in smoker patients, they did not reach the level observed in non-smoker patients.

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