Ginger extract release from 3D printed calcium phosphate scaffolds for bone regeneration

The development of multifunctional bone scaffolds that promote early osteogenesis and angiogenesis is a promising strategy for treating critical-sized bone defects. In this study, 3D-printed tricalcium phosphate (3DP TCP) scaffolds were loaded with ginger extract, a natural compound with known anti-inflammatory and regenerative properties. In vitro release study shows sustained ginger extract release over 28 days, with accelerated release under acidic conditions. Ginger extract enhanced osteoblast viability (1.3-fold at day 11), upregulates osteogenic genes including BGLAP (6.3-fold), RUNX2 (4.9-fold), and ALPL (8.1-fold), while supresses osteoclast activity by downregulating RANKL (up to 11-fold). TRAP assay, resorption pit analysis, and actin ring staining confirm reduced osteoclastogenesis. Angiogenesis study showed a 7.5-fold increase in endothelial tube formation and a 19 % enhancement in vitro wound healing. In vivo, ginger extract-loaded scaffolds implanted in rat distal femur defects shows increase in new bone formation, with SRBS staining showing 38.1 % bone area compared to 19.3 % in control, and Masson-Goldner staining showing 43.3 % mineralized bone area versus 25.9 % in control. These results underscore the potential of ginger extract-loaded 3DP TCP scaffolds as a bioactive platform for enhancing bone regeneration through osteoinduction, anti-resorptive effects, and angiogenesis.