Accelerated Bone Regeneration by Gold-Nanoparticle-Loaded Mesoporous Silica through Stimulating Immunomodulation

Bone repair and regeneration are greatly influenced by the local immune microenvironment. In this regard, the immunomodulatory capability of biomaterials should be considered when evaluating their osteogenic effects. In this study, we investigated the modulatory effects of gold nanoparticle (AuNP)-loaded mesoporous silica nanoparticles (Au-MSNs) on macrophages and the subsequent effects on the behavior of osteoblastic lineage cells. The results demonstrate that Au-MSNs could generate a favorable immune microenvironment by stimulating an anti-inflammatory response and promoting the secretion of osteogenic cytokines by macrophages. As a result, there is an enhancement of osteogenic differentiation in preosteoblastic MC3T3 cells as assessed by the increased expression of osteogenic markers, alkaline phosphatase (ALP) production, and calcium deposition. The immunomodulatory effects and direct osteogenic stimulation by Au-MSNs synergistically increased the osteogenic differentiation capability of MC3T3 cells as a result of crosstalk between Au-MSN-conditioned macrophages and Au-MSN-treated osteoblasts in a coculture system. An in vivo study further revealed that Au-MSNs could accelerate new bone formation in a critical-sized cranial defect site in rats based on computed tomography analysis and histological examination. Together, this novel Au-MSNs could significantly promote osteogenic activity by modulating the immune microenvironment, showing its therapeutic potential for bone tissue repair and regeneration.