The Loading of Dipyridamole and Calcium Sulfate into the Gelatin-Coated Porous Bioceramics to Synergistically Regulate Segmental Bone Regeneration

The treatment of large segmental bone defects has always been a medical challenge. Although various methods have been developed, each of them has its own drawbacks. To overcome the drawbacks, in situ tissue regeneration has bright prospects. Herein, we developed dipyridamole (D)/calcium sulfate (CS)-loaded, gelatin (G)-coated porous β-tricalcium phosphate (TCP) scaffolds using an indirect 3D printing and surface coating method to treat the 15 mm ulnar bone defects of rabbits. In vitro simulation experiments demonstrated that the as-prepared scaffolds could establish a dynamic acidic microenvironment with relative and variable concentrations of D, calcium ion, and phosphate anion. In vitro mesenchymal stem cell (MSC) coculture experiments displayed that four components, G, D, CS and TCP, could synergistically regulate the adhesion, proliferation, recruitment, migration, and osteogenic differentiation of MSCs. In vivo experiments displayed that the as-prepared scaffolds could recruit and capture endogenous MSCs, mediate the ulnar bone defects to bridge within 12 weeks, and match a desirable degradation rate. The as-prepared scaffolds with high in situ osteogenic activity are attributable to the synergistic effect of four components, which regulated the osteoblastic-osteoclastic imbalance of the bone remodeling cycle.