A β-Si₃N₄/HA composite materials with biomimetic mineralized CaCO₃ coating promote angiogenesis and bone regeneration...

The local immune microenvironment within bone defects dynamically orchestrates bone regeneration through intricate interactions between immune cells and bone marrow mesenchymal stem cells (BMSCs). Hydroxyapatite (HA), a commonly used bioceramic to mend bone defects, lacks the capacity to effectively control the crucial change in macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2). Its inherent biological inertness may consequently affect early inflammatory responses and subsequent tissue repair processes. To overcome this limitation and enhance the immunomodulatory capability of HA, we devised a dual modification strategy that combines bulk modification with surface functionalization. First, β-Si₃N₄ was incorporated as an active silicon ion source to construct a β-Si₃N₄/HA composite ceramic substrate. Subsequently, this substrate underwent surface modification via Si₃N₄ hydrolysis to drive biomimetic mineralization, forming a calcium carbonate (CaCO₃) coating and yielding a β-Si₃N₄/HA@CaCO₃ composite material. This composite exhibited excellent biocompatibility. Crucially, under simulated inflammatory conditions, it effectively induced macrophages the pro-inflammatory M1 state to the anti-inflammatory M2 state. This immunomodulatory shift generated a pro-osteogenic immune microenvironment, which significantly enhanced rat BMSCs' (rBMSCs') osteogenic differentiation. Additionally, through indirect immunomodulation, the altered immunological environment stimulated angiogenesis in human umbilical vein endothelial cells (HUVECs). Collectively, these in vitro findings indicate that the β-Si₃N₄/HA@CaCO₃ composite material holds great promise for overcoming the biological inertness of traditional bioceramics. It represents a comprehensive, potential strategy for bone defect repair that synergistically combines mechanical compatibility, immunomodulation, and facilitation of multi-tissue regeneration.