Periodontal regeneration requires coupled angiogenesis and osteogenesis, while current strategies to promote angiogenesis face limitations such as poor cytokine stability and safety concerns. Nanosilicates (nSi), as bioactive nanomaterials with potent properties, show promise for enhancing bone regeneration via osteogenic pathways. However, their pro-angiogenic potential and precise mechanisms, particularly within the periodontal microenvironment, remain poorly understood. This study addresses this knowledge void by introducing nSi into rat periodontal defects, revealing significantly enhanced vascular network formation and bone repair in vivo. Crucially, through intervention in relevant signalling pathways, this research provides the first evidence for the molecular mechanism underlying nSi-induced angiogenesis in endothelial cells. We demonstrate that nSi regulate microtubule homeostasis via the MAPK-mediated MAP4 signalling pathway, facilitating STAT3 nuclear translocation and ultimately promoting angiogenic differentiation. This mechanistic elucidation fills a critical gap in understanding the nSi–cytoskeleton–transcriptional regulation axis. These findings offer fundamental insights to guide the rational design and optimisation of nSi-based biomaterial systems for vascularised periodontal regeneration.
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2025 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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