Supplementary file 1_MicroRNA-driven periodontal immune homeostasis and tissue regeneration: from regulatory networks to engineering translation.docx

It then examines the core functions of miRNAs across three dimensions—osteogenic/osteoclastic differentiation, immune homeostasis, and angiogenesis—analyzes their molecular interactions with competing endogenous RNAs (ceRNAs), summarizes the intercellular communication functions of miRNAs mediated by extracellular vesicles (EVs), and provides a graded synthesis of the research evidence for core miRNAs. At the translational engineering level, this review comprehensively surveys five strategies: miRNA mimic delivery, miRNA inhibition and blockade, indirect regulation of endogenous expression, engineered EV delivery, and DNA nanorobots.

On this basis, it identifies three core bottlenecks constraining the field—the complexity of molecular regulatory networks, insufficient adaptability of delivery systems, and an incomplete preclinical validation framework—and proposes a spatiotemporally coordinated model for periodontal regeneration based on three sequential stages of intervention: “inflammation regulation, osteogenic–vascular coupling, and tissue maturation and remodeling.” This review aims to overcome the fragmentation of previous research by providing a systematic framework for elucidating the immune regulatory mechanisms of miRNA-mediated periodontal regeneration, developing smart responsive scaffolds, and conducting preclinical validation in large animals, while advancing the clinical translation of miRNA-based multi-target regulatory strategies in periodontal regeneration.</p>