Stem cell-based bone repair in vivo relies on both the osteogenic differentiation of stem cells and the immune activities of immune cells. The lack of effective means to simultaneously tune the local osteoinductive and inflammatory microenvironments is one of the major obstacles to the treatment of bone defects. Herein, we report calcium nervonate nanoparticles as a dual-functional therapeutic platform combining osteoinduction and immunomodulation for bone regeneration. Calcium nervonate nanoparticles will be decomposed into calcium ion (Ca²⁺) and nervonic acid in acidic lysosomes after being taken up by cells. The released Ca²⁺ and nervonic acid can then contribute to the osteogenic and anti-inflammatory microenvironments, respectively. In vitro experiments demonstrate that calcium nervonate nanoparticles promote the osteogenic differentiation of mesenchymal stem cells and alleviate the inflammatory response caused by lipopolysaccharide-activated macrophages. In vivo bone defect repair experiments confirm that calcium nervonate nanoparticles have better performance for promoting bone regeneration than Ca²⁺ or nervonic acid alone. This work develops a new bone regeneration approach by exploring calcium nervonate nanoparticles as a dual-functional platform, which has great promise in repairing bone defects.

基于干细胞的体内骨修复依赖于干细胞的成骨分化和免疫细胞的免疫活性。缺乏同时调节局部骨诱导和炎症微环境的有效手段是治疗骨缺损的主要障碍之一。在此，我们报告了神经酸钙纳米粒子作为一种双重功能治疗平台，结合了骨诱导和免疫调节以促进骨再生。神经酸钙纳米粒被细胞摄取后，在酸性溶酶体中分解为钙离子（Ca ^{2+ ）和神经酸。}释放的 Ca ²⁺和神经酸可以分别促进成骨和抗炎微环境。体外实验表明，神经酸钙纳米粒促进间充质干细胞的成骨分化，减轻脂多糖激活的巨噬细胞引起的炎症反应。体内骨缺损修复实验证实，神经酸钙纳米粒子比单独的Ca ²⁺或神经酸具有更好的促进骨再生的性能。这项工作通过探索神经酸钙纳米粒子作为双功能平台，开发了一种新的骨再生方法，在修复骨缺损方面具有巨大前景。