MicroRNA146a-loaded Magnesium Silicate Nanospheres promote bone regeneration with inflammatory microenvironment

Abstract The reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a clinical challenge as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSN) to load a nucleic acid drug - microRNA146a-5p (miR146a), fabricating a nanobiomaterial complex MSN-miR146a with high oligo transfection efficiency. This complex showed a potent promoting effect on osteogenic differentiation of human dental pulp stem cells with upregulated expression of osteogenesis markers including alkaline phosphatase, collagen Ⅰ, Runt-related transcription factor 2, osteopontin and Osterix. Additionally, miR146a was observed to have an anti-inflammatory effect by reducing CD40high M1 pro-inflammatory mouse bone marrow derived macrophages under lipopolysaccharide stimulation, with MSN simultaneously upregulating Arginase-1high or CD163high M2 pro-regenerative BMMs. The osteogenic-promoting and immunoregulatory effects of MSN-miR146a were further validated in a mouse-infected mandibular bone defect model delivered by photocuring hydrogel. Collectively, the MSN-miR146a complex revealed great potential in treating inflammatory irregular oral-maxillofacial bone defects.