BackgroundMany encouraging studies confirmed the ability of Zinc Oxide Nanoparticles (ZnONPs) in accelerating bone growth and mineralization. The use of Platelet Rich-Fibrin (PRF) as a sole filling material for large segmental bone defects remains questionable. The objectives are to investigate the regenerative efficacy of autologous Platelet Rich-Fibrin (PRF) and Zinc Oxide Nanoparticles (ZnONPs) in repairing large segmental bone ulnar defects in a randomized controlled study in rabbits using computed tomographic interpretations. A 12 mm critical size defect was surgically induced in the ulna of 30 rabbits (n = 10/ group). In the control group, the defect was left empty. In the PRF group, the defect is filled with PRF. In the PRF/ZnONPs group, the defect is filled with PRF that was inoculated with 0.1 ml of 0.2% ZnONPs. Radiologic healing capacity was evaluated at the first, second, and third postoperative months.ResultsStatistical analysis showed significant differences in the radiologic healing scores between the groups (P = 0.000–0.0001) at all-time points (P = 0.000–0.047) during the study.ConclusionRabbits in the PRF/ZnONPs group showed the highest appreciable bone quality and quantity followed by the PRF group with high quantity but low bone quality meanwhile, rabbits in the control group showed minimal quantity but medium bone quality. Interestingly, the addition of ZnONPs to PRF can accelerate the healing of ulnar critical-size defects in rabbits.