3D-printed tricalcium phosphate scaffolds with Quercetin-zinc chelation for osteogenic, antibacterial and anti-osteosarcoma activity.

Craniomaxillofacial bone defects and implant-related infections require materials that support regeneration while providing localized therapeutic action. Quercetin offers osteogenic, antibacterial, and anticancer activity, but poor stability and bioavailability limit direct use. To address this, a Quercetin-zinc (Q-Zn2+) complex is loaded onto 3D-printed (3DP) tricalcium phosphate (TCP) scaffolds, where zinc coordination stabilizes Quercetin through metal-ligand interactions and enables controlled release. The release behavior of Q-Zn2+ from 3DP TCP and its antibacterial effects remain unexplored. Characterization of the complex shows that Zn2+ chelates with Quercetin's hydroxyl and carbonyl groups. Release studies at pH 5.0 and pH 7.4 show sustained delivery of Quercetin over 24 days, reaching 16% release at pH 5.0 and 5% at pH 7.4 for complexed Quercetin. In vitro evaluation shows that Q-Zn2+-loaded scaffolds increase osteoblast viability by 42%, reduce osteosarcoma viability by ∼55%, and achieve 93% inhibition of Staphylococcus aureus compared to TCP control. Zn2+ chelation stabilizes Quercetin release while improving osteoblast viability and suppressing bacterial and osteosarcoma growth from 3DP TCP scaffolds. This approach offers a route for controlled therapeutic delivery of Quercetin in calcium phosphate bone graft materials.