Magnetic hydroxyapatite nanobelt-stem cell hybrid spheroids for remotely patterning bone tissues

The low survival rate and poor differentiation efficiency of stem cells, as well as the insufficient integration of implanted stem cells, limit the regeneration of bone defects. Here, we have developed magnetic ferroferric oxide-hydroxyapatite-polydopamine (Fe₃O₄-HAp-PDA) nanobelts to assemble mesenchymal stem cells (MSCs) into a three-dimensional hybrid spheroid for patterning bone tissue. These nanobelts, which are featured by their high-aspect ratio and contain Fe₃O₄ nanospheres with a PDA coating, can be manipulated by a magnetic field and foster enhanced cell-nanobelt interactions. This strategy has been demonstrated to be effective for both bone marrow mesenchymal stem cells and adipose-derived mesenchymal stem cells, enabling remote manipulation of stem cell spheroids and efficient spheroid fusion, which in turn accelerates osteogenic differentiation. Consequently, this methodology serves as an efficient and general tool for bone tissue printing and can potentially overcome the low survival rate and poor differentiation efficiency of stem cells, as well as mismatched interface fusion issues.