The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin‐8 (IL‐8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL‐8, during which neutrophils are recruited to the implanted site and are N2‐polarized, which then secrete stromal cell‐derived factor‐1α (SDF‐1α) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF‐1/CXCR4 (C‐X‐C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'‐kinase (PI3K)/Akt pathway and β‐catenin‐mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil‐initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.

Massive blood loss and bacterial infection are major challenges for global public health. In this study, we developed tannic acid (TA)-loaded mesoporous silica (MS) nanoparticles for both hemorrhage control and effective antibacterium via covalent conjugation and electrostatic adsorption. The TA-absorbed MS could significantly relieve hemolysis and facilitate blood contact, therefore efficiently promoting protein adhesion and the contact activation pathway of the coagulation cascade with desirable hemostasis. Comparably, with increasing TAs absorption, the bleeding control and antibacterial performance were improved simultaneously, especially for 15TMS. Hemostasis tests demonstrated that the 15TMS could reduce the hemostatic time by 65% both in vitro and in vivo, with lower blood loss and could exhibit better antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis as well as promote wound healing. However, the TAs-loaded MS via chemical grafting (15T-g-MS) significantly reduced the surface area of MS, by replacing the Si–OH on the MS, and thus it exhibited worse bleeding control and antibacterial efficacy than 15TMS. Furthermore, all the samples exhibited excellent cell viability. Based on these results, it can be concluded that the 15TMS would be a promising material platform for designing hemostats in more extensive clinical application.