Periodontitis influences systemic health through mechanisms that extend far beyond the periodontal pocket, yet the vehicles that mediate this dissemination remain incompletely defined. Within the “red complex” of periodontitis, Tannerella forsythia (Tf) has long been overshadowed by Porphyromonas gingivalis and Treponema denticola, and its extracellular vesicles (EVs) have been correspondingly neglected. This review synthesizes a decade of evidence to reposition Tf EVs as a distinct nanoscale virulence-delivery platform. Their biogenesis couples outer-membrane budding to the type IX secretion system (T9SS), and the crystalline surface layer (S-layer) appears to be actively reprogrammed—rather than passively shed—to accommodate vesicle curvature, a mechanism so far supported by compositional evidence. Their cargo is selectively enriched in T9SS substrates, TonB-dependent receptor/SusD-like nutrient-acquisition proteins, and extensively O-glycosylated virulence factors. Mechanistically, as demonstrated directly at the vesicle level in cellular models, Tf EVs engage Toll-like receptor 2 (TLR2), autonomously prime and activate the inflammasome, and drive IL-12-dependent Th1 polarization. These properties define a “purely pro-inflammatory” immunological identity that distinguishes Tf EVs from those of P. gingivalis and Fusobacterium nucleatum. Signature cargo, including BspA, miropin, and PepO, suggests potential links between Tf EVs and cardiovascular, articular, and pulmonary diseases; however, these systemic associations are currently inferred mainly from whole-cell, isolated-virulence-factor, or epidemiological evidence, rather than from direct Tf EV-level experiments, and are therefore presented here as testable hypotheses. We critically appraise isolation and standardization practices, delineate priority gaps such as unverified vesicle subtypes and unexplored small RNA cargo, and propose a four-step roadmap from subtype isolation to clinical cohorts. Tf EVs warrant recognition as an independent research object and a candidate druggable target for periodontitis, whereas their contribution to its systemic comorbidities awaits direct causal validation at the EV level.

Introducing reversible covalent linkages, such as Schiff base bonds and disulfide bonds, into natural polymer networks like chitosan and hyaluronic acid has become an important research direction in the hydrogel field. This strategy seeks to reconcile the limited strength of physically crosslinked gels with the poor adaptability of permanently crosslinked gels. Although dynamic covalent networks, self-healing natural-polymer hydrogels, and injectable oral or periodontal materials have each been reviewed, these topics are often treated separately. The unresolved question addressed here is how to select dynamic bonds and regulate their exchange kinetics under the coupled constraints of the oral cavity, including salivary washout, masticatory friction, local pH/ROS/glucose fluctuations, required retention and degradation periods, and manufacturability. This review therefore focuses on dynamic covalent-crosslinked hydrogels built from natural polymer backbones and evaluates three mainstream bond types: Schiff base bonds, disulfide bonds, and boronic ester bonds. Following an oral-specific design framework of “pathological signals—bond response—property trade-offs—scenario fit—translation bottlenecks”, it examines local drug delivery and tissue-repair applications in periodontitis and oral ulcers and discusses dentin hypersensitivity and pulp protection only as potential extension directions. Diagnostic sensing, molecular imaging, and receptor-mediated targeting are outside the evidence base of this review and are not claimed as established applications. The review summarizes trade-off rules between mechanical performance and dynamic functions and identifies bottlenecks in multi-network regulation, sterilization, and clinical translation. Its added value lies in linking bond chemistry to oral-specific design constraints, rather than cataloguing hydrogel examples alone.