SustainedFisetin Release Prevents Orthodontic Ti-6Al‑4VScrew Failure by Suppressing Peri-Implantitis and Alveolar Bone Resorption

In clinical practice, mini-screws of titanium-6-aluminum-4-vanadium alloy with an extra low interstitial (ELI) grade (Ti-6Al-4V ELI) are widely used as orthodontic anchorages. However, in orthodontic treatment, Ti-6Al-4V mini-screw failure because of peri-implantitis is a major challenge. To prevent damage caused by peri-implantitis, we developed a novel Ti-6Al-4V disc/screw coated with poly(lactide-<i>co</i>-glycolide) incorporating fisetin, a naturally occurring flavonoid with anti-inflammatory and antiosteoclastogenic/osteogenic properties. Sustained fisetin release from the Ti-6Al-4V disc and its anti-inflammatory and antiosteoclastogenic/osteogenic differentiation properties were demonstrated using in vitro cell culture experiment. In addition, in a rat model of peri-implantitis, sustained fisetin release from the Ti-6Al-4V screw suppressed inflammation progression, reduced alveolar bone resorption, and stabilized screw movement. These findings highlight sustained fisetin-release Ti-6Al-4V screws as a promising strategy for enhancing orthodontic mini-screw stability and success through peri-implantitis prevention.