Longitudinal proteomic analysis of GCF in regenerative healing of molar furcation degree II defects treated with OFD, EMD, or A-PRF+: a pilot study

This study evaluated associations between protein expression and postoperative healing scores following three periodontal regenerative procedures (Open Flap Debridement–OFD, Enamel Matrix Derivative–EMD, Advanced Platelet Rich Fibrin–A-PRF+) in molar degree II furcations over six months. Associations between baseline systemic biochemical parameters and six-month clinical outcomes were also assessed.Eighteen patients were randomly assigned to control (OFD), EMD, or A-PRF + groups. Baseline plasma biomarkers were modeled on probing depth (PD), clinical attachment level (CAL), and alveolar bone level (ABL) at six months. Gingival crevicular fluid (GCF) samples were analyzed using the Olink® Target 96 Immuno-Oncology panel at day 3, weeks 1, 2, 6, and months 3 and 6. Multivariable linear regressions identified proteins associated with the modified Early Wound Healing Index (mEHI) per treatment.Seventeen patients completed follow-up. HDL- and LDL-cholesterol and creatinine were negatively associated with PD, CAL, and ABL improvements (p < 0.05). At early timepoints, CASP-8, IL-8, and LAP TGF-β1 showed stronger associations with mEHI in A-PRF + than OFD or EMD, while ARG-1 and TRAIL demonstrated treatment-specific patterns over time. No differences were observed at month 6.High baseline cholesterol and creatinine may impair periodontal regeneration. Distinct proteomic signatures suggest differential biological pathways underlying healing across OFD, EMD, and A-PRF + procedures.