Resolution Failure in Periodontal Diseases: Dysregulated Pro-resolving Mechanisms in Chronic Inflammation and Tissue...

Periodontitis is a highly prevalent chronic inflammatory disease characterized by irreversible destruction of the tooth-supporting tissues. Although classically interpreted as the consequence of excessive inflammation that drives microbial dysbiosis, accumulating experimental and clinical evidence indicates that periodontitis can be more precisely described as a disorder of failed inflammatory resolution. In periodontal tissues-constantly exposed to microbial challenge-resolution is not a terminal event but a constitutive biological requirement essential for maintaining tissue homeostasis. This chapter examines the molecular and cellular mechanisms through which pro-resolving pathways become dysregulated in periodontitis, with particular emphasis on imbalances in lipid mediator networks, defective biosynthetic class switching, impaired receptor-mediated signaling, altered leukocyte fate decisions, and disruption of osteoimmune coupling. We further discuss how these resolution defects are functionally expressed across immune, stromal, and bone compartments, and how they reshape the inflammatory microenvironment and host-microbiome interactions. Finally, we evaluate the implications of these mechanisms for resolution pharmacology, highlighting how restoration of endogenous termination and repair programs-rather than suppression of inflammatory initiation-offers a biologically grounded therapeutic paradigm. Collectively, this chapter positions periodontitis as both a disease-specific manifestation of resolution failure and a tractable translational model for advancing resolution-based therapeutic strategies with potential relevance beyond oral tissues.