Effect of Hydroxyapatite Nanowires on Formation and Bioactivity of Osteoblastic Cell Spheroid

Compared with traditional high-density cell spheroids, which are more prone to core necrosis, nanowires effectively improve the biological activity of core cells in spheroids, emanating more innovations for optimizing the internal cell survival environment and providing differentiation signals. In this study, hydroxyapatite nanowires (HAW), which provide numerous material exchange channels for internal cells by interpenetrating into cell spheroids, were added to osteoblast precursor (MC3T3-E1) cell spheroids. HAW, synthesized using the hydrothermal method, was used as a regulatory material to prepare uniformly sized 3D composite spheroids with good biological activity. Subsequently, material characterization and biocompatibility tests were performed on HAW, and the biological activity and osteogenic differentiation ability of the cell spheroids were tested. Notably, in 2D coculture, HAW displayed a certain attraction to MC3T3-E1 cells and promoted cell aggregation toward it. The content of HAW determined whether composite cell spheroids can form aggregated spherical structures, and incorporation of HAW alleviated core necrosis and enhanced the osteogenic phenotype. In summary, these findings indicate that the prepared HAW-bone cell composite spheroids can potentially be used as building blocks for the construction of large high-density biomimetic tissues and organoids using 3D bioprinting technology.