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.

Established oral squamous cell carcinoma (OSCC) remains constrained by local recurrence, inadequate lesion exposure, systemic toxicity, and therapy resistance. This narrative review evaluates a proposed microneedle–small extracellular vesicle (sEV) system for localized adjunctive treatment in three preclinical contexts: postoperative residual-disease control, local immunomodulation/checkpoint combination, and chemoradiotherapy sensitization. Direct evidence for the combined microneedle–sEV system in OSCC is not yet available; the analysis therefore integrates OSCC-specific sEV mechanisms with oral-mucosal microneedle and cross-disease engineering studies. We focus on whether the proposed microneedle–sEV system can preserve sEV potency, achieve reproducible local delivery, and meet oncologic-safety, manufacturing, and repeated-dose oral-safety requirements. The review provides a preclinical decision framework and comparator-based development criteria rather than a claim of clinical readiness.

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.

Ablative and non-ablative energy-based procedures—lasers, intense pulsed light, radiofrequency and ultrasound—rejuvenate skin by inflicting controlled, mechanism-specific injury, yet the resulting perturbation can drive erythema, barrier disruption, dyschromia and, occasionally, scarring. Hydrogel dressings are increasingly used to manage this recovery window, but design principles specific to the post-procedure microenvironment remain scattered. This narrative review synthesises how each energy modality perturbs the cutaneous microenvironment across five coupled dimensions—thermal load, barrier integrity, inflammation, pigmentation and a merged microbiome–oxidative axis—and maps six hydrogel design strategies onto these perturbations: cooling and moist barrier restoration, antioxidant and bioactive gas delivery, immunomodulation, antibacterial and photothermal design, anti-pigmentation strategies, and active delivery against aberrant remodeling. We then grade the evidence with an author-defined, scenario-adapted rubric, revealing a steep evidence cliff: 133 unique cited source records were reconciled, of which 85 original studies were graded; only three randomized trials tested gel-based formulations directly after energy-based procedures (two tested water-swollen hydrogels under the strict definition; the cliff conclusion is unchanged), and 41 of these 85 graded original studies remain at the in vitro or small-animal stage. The other 48 records comprise 34 reviews and 14 context, methods, regulatory, or out-of-scope records, each with an explicit reason for non-grading. The article uses a structured citation-level evidence audit and is not a systematic or scoping review. Evidence from burns, chronic wounds, injectable fillers, melasma, ex vivo skin, or infected animal wounds is treated as indirect and is not used to infer efficacy after aesthetic energy-based procedures. Finally, we dissect translational bottlenecks—regulatory classification and the resulting scissors gap between laboratory innovation and registration feasibility, the sterilization paradox, and manufacturing scale-up—and propose a staged roadmap from bench to clinic. Hydrogels are poised to become precision recovery platforms rather than passive dressings, provided that design, evidence and regulation advance together. Personalized, closed-loop and bioactive-cargo dressings remain research directions for prospective, adequately controlled, procedure-specific evaluation rather than established clinical capabilities.