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Critical-size bone defects are an important problem in clinical practice, which usually occurs in severe trauma, or tumor resection, and cannot heal completely and autonomously. Implantation of grafts is often required to promote the regeneration of critical-size bone defects. Metal ions play an important role in human health, as they affect the body's metabolism and the tissue function. Strontium ions (Sr 2+ ) can promote osteogenesis and angiogenesis. Herein, we prepared nano-hydroxyapatite (nHA)/ chitosan (CS) composite microspheres with a uniform particle size distribution and an extracellular matrix-like nanofiber structure using microfluidic technology and direct alkali-induced gelation. Strontium ions were stably added into the microspheres by using polydopamine (PDA) to chelate metal ions forming a bone repair material (nHA/CS@PDA-Sr) with good bioactivity. The coordination reaction of PDA can effectively control the release of strontium ions and avoid the negative effects caused by the high strontium concentration. Our in vitro experiments showed that the composite microspheres had good biocompatibility and that the PDA coating promotes cell adhesion. The slow release of strontium ions can effectively promote mesenchymal stem cells osteogenic differentiation and the vascularization of endothelial cells. In addition, we injected composite microspheres into cranial defects of rats to evaluate osseointegration in vivo. The results showed that nHA/CS@PDA-Sr could effectively promote bone regeneration in the defect area. This study demonstrates that composite microspheres stimulate bone repair providing a promising way for bone-defect regeneration.

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