3D-Printed Scaffolds of Porous Amorphous Calcium Phosphate Nanospheres Loaded with Quercetin for Promoting Bone Repair via Synergistic Osteogenesis and Immunoregulation

The implantation of 3D-printed scaffolds for bone repair could be ineffective due to the early inflammatory response. In this work, porous amorphous calcium phosphate (ACP) nanospheres were employed to not only load quercetin (Que) but also mix with octacalcium phosphate (OCP) to form biphasic calcium phosphate (BCP). Afterward, the drug-loaded nanospheres (AQ) were combined with BCP and sodium alginate (SA) to fabricate the AQ-BCP/SA scaffolds with an interconnected structure for solving the anti-inflammatory challenge and thus promoting osteogenesis. The scaffolds obtained excellent mineralizing properties due to the interaction of ACP and the OCP in the component. Additionally, the stable and continuous release of Que enabled the scaffolds to synergistically induce osteogenesis and immunoregulation. The scaffolds were capable of directly promoting osteogenic differentiation in vitro by upregulating the expression of related genes Runx2, ALP, BMP2, and OCN. Meanwhile, they were also demonstrated to be beneficial in immunoregulation by inducing macrophages to transform into M2 polarization rather than M1 polarization. In vivo evaluation also confirmed the significant osteogenic and immunoregulatory effects of the scaffolds, which were helpful for ideal bone repair. Thus, the AQ-BCP/SA scaffolds have the potential to be applied in the future bone tissue engineering area.