Burn wounds exhibit a dynamic and heterogeneous microenvironment characterized by altered pH, excessive reactive oxygen species (ROS), dysregulated protease activity, and infection-associated signals, providing potential triggers for stimuli-responsive hydrogels. However, in vitro responsiveness does not necessarily indicate effective activation under actual burn conditions, and therapeutic efficacy in burn models alone cannot confirm in situ triggering. This review therefore examines burn-responsive hydrogels through the framework of microenvironmental signal–material response–network transformation–therapeutic output. We discuss endogenous signals, including pH, ROS, and matrix metalloproteinases, together with externally controllable stimuli such as temperature, near-infrared light, and ultrasound. Molecular functionalization, dynamic crosslinking, and multi-network architectures are analyzed in relation to wound adaptability and therapeutic outputs, including antibacterial activity, oxidative-stress regulation, and tissue regeneration. Particular emphasis is placed on distinguishing material-level responsiveness, therapeutic efficacy in burn models, and in situ activation within the burn microenvironment. Future studies should quantitatively match pathological signal ranges with material activation thresholds while balancing response fidelity, wound adaptability, biosafety, manufacturability, and long-term therapeutic efficacy to facilitate clinical translation.

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.

Background: Branched-chain amino acids (BCAAs) regulate muscle protein metabolism, yet the systematic characterization of their dose-dependent morphological effects on exercised skeletal muscle remains limited. This study investigated the dose–response relationship between BCAA supplementation and skeletal muscle adaptations in exercise-trained mice. Methods: Seventy male Kunming mice were randomly assigned to seven groups (n = 10): a background group (no exercise), a control group (exercise + saline), and five exercise groups receiving BCAAs at 1–5 g/kg/day via intragastric gavage. Mice in the exercise groups performed 45 min of swimming daily (6 days/week) for 50 days. Gastrocnemius muscles were processed using hematoxylin–eosin staining, Masson trichrome staining, Gomori aldehyde fuchsin staining, and transmission electron microscopy. Data were analyzed using one-way ANOVA with Dunnett’s post hoc test. Results: BCAA supplementation increased gastrocnemius wet weight-to-body weight ratios and promoted denser fiber packing in a dose-dependent manner up to 3–4 g/kg/day. Deep-staining fiber proportion (putatively type II-like) increased progressively with BCAA concentration, plateauing at doses ≥ 3 g/kg/day, while elastic fiber content continued to rise through 5 g/kg/day. Mitochondrial size decreased as mitochondrial number increased; membrane and cristae thickness peaked at 3 g/kg/day. Sarcomere length, myofibril diameter, sarcoplasmic reticulum size, and transverse tubule diameter exhibited increasing trends. Conclusions: These findings establish a parameter-specific dose–response framework for BCAA-induced muscle remodeling. A supplemental dose of 3 g/kg/day above background dietary intake represents an effective threshold for maximizing indices of hypertrophic gains and mitochondrial structural maturation potentially indicative of functional enhancement. Higher doses (≥4 g/kg/day) elicited additional benefits in fiber density, mitochondrial proliferation, and elastic fiber content. Supplemental BCAA dosing strategies above constant background intake should be tailored to target specific structural outcomes, with functional validation required to confirm physiological relevance.

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.