Gingerol-zinc complex loaded 3D-printed calcium phosphate for controlled release application

The therapeutic potential of natural medicines in treating bone disorders is well-established. Modifications in formulation or molecular structure can enhance their efficacy. Gingerol, an osteogenic active compound derived from ginger roots (Zingiber officinale), can form metal ion complexes. Zinc (Zn), a trace element that combats bacterial infections and promotes osteoblast proliferation, can be complexed with gingerol to form a G-Zn⁺² complex. This study investigates a porous 3D-printed (3DP) calcium phosphate (CaP) scaffold loaded with the G-Zn⁺² complex for drug release and cellular interactions. The scaffold is coated with polycaprolactone (PCL) to control the drug release. Diffusion-mediated kinetics results in 50% release of the G-Zn⁺² complex over 6 weeks. The G-Zn⁺² complex demonstrates cytotoxicity against MG-63 osteosarcoma cells, indicated by the formation of apoptotic bodies and ruptured cell morphology on the scaffolds. G-Zn⁺² PCL-coated scaffolds show a 1.2 ± 0.1-fold increase in osteoblast cell viability, and an 11.6 ± 0.5% increase in  alkaline phosphatase compared to untreated scaffolds. Treated scaffolds also exhibit reduced bacterial colonization against Staphylococcus aureus bacteria, highlighting the antibacterial potential of the G-Zn⁺² complex. The functionalized 3DP CaP scaffold with the G-Zn⁺² complex shows significant potential for enhancing bone regeneration and preventing infections in low-load-bearing applications.