β-Tricalcium phosphate nanoparticles induce macrophage polarization to M1-type through mitochondrial oxidative stress activation

β-Tricalcium phosphate (β-TCP), frequently employed for bone tissue regeneration, can induce inflammation during the initial phases of implantation within the organism. However, mechanisms by which β-TCP nanoparticles (NPs) cause this inflammatory response is rarely reported. This project aims to investigate the causes of the macrophage inflammatory response induced by β-TCP NPs. Here, macrophage-like RAW264.7 cells were co-cultured with conditioned medium containing β-TCP NPs to identify the pathways through which β-TCP NPs influence inflammation and polarization of macrophages. This effect is achieved by modulating mitochondrial oxidative stress in the immune microenvironment. The results demonstrated that β-TCP NPs caused mitochondrial swelling, increased intracellular calcium ions, reduced mitochondrial membrane potential, as well as decreased the level of adenosine triphosphate (ATP) and translocase of outer mitochondrial membrane 20 (TOMM20). These NPs further lead to mitochondrial oxidative damage. These alterations promoted the polarization of macrophage to M1-type. Exogenous mitochondrial-targeted Antioxidants could block this M1-type macrophage polarization. The findings of this work suggest that β-TCP NPs induce macrophage inflammation and contribute to M1 macrophage polarization, primarily through the activation of mitochondrial oxidative stress. These insights could guide the development of improved β-TCP formulations to mitigate inflammatory responses in bone regeneration applications.

Macrophages; Macrophagic inflammation; Mitochondria; Polarization; ROS production; β-TCP nanoparticles.