Shaping Orthodontics of the Future: Concepts and Implications from a Cellular and Molecular Perspective

Orthodontic tooth movement (OTM) is accompanied by sterile inflammation, a necessary biological process that facilitates tooth displacement but also contributes to adverse effects, including hyalinization and orthodontically induced external apical root resorption (OEARR). Despite advancements in orthodontic therapies, the inflammatory response-regulated by dynamic interactions between tissue-specific cells and their molecular mediators-remains a critical factor influencing treatment outcomes. This review summarizes the current understanding of the cellular and molecular mechanisms underlying OTM, with a focus on how these insights can support the development of targeted therapeutic strategies. These include cell- and molecule-based therapies, biomaterial-mediated delivery systems, and applications of artificial intelligence (AI). Notably, AI offers promising opportunities for modeling and simulating biological responses, enabling the optimization of individualized treatment planning. We further discuss current clinical practices and highlight emerging experimental findings, with an emphasis on unresolved research questions pivotal to improving therapeutic efficacy and reducing complications such as OEARR. This comprehensive overview aims to inform future directions in orthodontics by integrating mechanistic knowledge with technological innovation.