Fullerol-hydrogel microfluidic spheres for in situ redox regulation of stem cell fate and refractory bone healing

The balance of redox homeostasis is key to stem cell maintenance and differentiation. However, this balance is disrupted by the overproduced reactive oxygen species (ROS) in pathological conditions, which seriously impair the therapeutic efficacy of stem cells. In the present study, highly dispersed fullerol nanocrystals with enhanced bioreactivity were incorporated into hydrogel microspheres using one-step innovative microfluidic technology to construct fullerol-hydrogel microfluidic spheres (FMSs) for in situ regulating the redox homeostasis of stem cells and promoting refractory bone healing. It was demonstrated that FMSs exhibited excellent antioxidant activity to quench both intracellular and extracellular ROS, sparing stem cells from oxidative stress damage. Furthermore, these could effectively promote the osteogenic differentiation of stem cells with the activation of FoxO1 signaling, indicating the intrinsically osteogenic property of FMSs. By injecting the stem cells-laden FMSs into rat calvarial defects, the formation of new bone was remarkably reinforced, which is a positive synergic effect from modulating the ROS microenvironment and enhancing the osteogenesis of stem cells. Collectively, the antioxidative FMSs, as injectable stem cell carriers, hold enormous promise for refractory bone healing, which can also be expanded to deliver a variety of other cells, targeting diseases that require in situ redox regulation.