Regenerative endodontic approaches for immature necrotic permanent teeth must balance biological efficacy, clinical practicality and long-term aesthetic outcomes. This study evaluates a novel regenerative protocol using autologous advanced platelet-rich fibrin plus (A-PRF+) scaffold sealed exclusively with glass ionomer cement (GIC) and compares it to conventional calcium hydroxide apexification used as the control. Twenty-eight patients were prospectively enrolled and followed for 12 months alongside a retrospectively selected historical control group. Outcomes were evaluated through standardised blinded clinical, radiographic and vitality assessments. The A-PRF+ protocol demonstrated significantly faster periapical healing, superior root lengthening, increased dentinal wall thickness and apical closure (p < 0.0001), with excellent aesthetic outcomes and no reported tooth discolouration. Pulpal blood flow measured by laser Doppler flowmetry indicated vitality restoration in 93% of cases. Preliminary linear regression identified treatment duration as a significant predictor of apical closure (p < 0.0001), with possible enhancement by additional patient-specific variables. These findings validate the A-PRF+ protocol as a highly effective, aesthetically favourable and predictable regenerative strategy, establishing a new benchmark for the management of immature necrotic teeth and laying the foundation for personalised predictive endodontic care. Future studies should include multicentre randomised controlled trials to confirm long-term clinical sustainability and generalisability.