Background: The aim of this feasibility study was to investigate the concentration level of CCL-20/MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin in the Peri-Implant Crevicular Fluid (PICF), from patients diagnosed with peri-implant mucositis and peri-implantitis, and to compare them with PICF from patients with healthy implants. Methods: Participants with at least one dental implant with healthy peri-implant tissues, peri-implant mucositis, or peri-implantitis were included. PICF was collected using paper strips from healthy and diseased peri-implant sites (n = 19). Biomarker levels were analyzed using a custom Multiplex ELISA Assay Kit. Results: In comparison to peri-implant health, the peri-implant mucositis group showed an increased concentration of CCL-20 MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin. The peri-implantitis group had the lowest median concentration of Osteoprotegerin (1963 ng/mL); this group had a similar concentration of RANKL (640.84 ng/mL) when compared to the peri-implant health group. BAFF/BLyS (17.06 ng/mL) showed the highest concentration in the peri-implantitis group. Conclusions: This feasibility study suggests that IL-23 and RANKL may help to elucidate the pathogenesis during the conversion from peri-implant health to peri-implantitis. Further research is required in BAFF/BLyS for the early diagnosis of peri-implantitis.

The need to predict, diagnose and treat peri-implant diseases has never been greater. We present a systematic review of the literature on the changes in the expression of biomarkers in peri-implant crevicular fluid (PICF) before and after treatment of peri-implantitis. Bacterial composition, clinical and radiographic parameters, and systemic biomarkers before and after treatment are reported as secondary outcomes. A total of 17 studies were included. Treatment groups were non-surgical treatment or surgical treatment, either alone or with adjunctive therapy. Our findings show that non-surgical treatment alone does not influence biomarker levels or clinical outcomes. Both adjunctive photodynamic therapy and local minocycline application resulted in a reduction of interleukin (IL)-1β and IL-10 twelve months after treatment. Non-surgical treatments with adjunctive use of lasers or antimicrobials were more effective at improving the clinical outcomes in the short-term only. Access flap debridement led to matrix metalloproteinase (MMP)-8 and tumour necrosis factor-α reduction twelve months post-surgery. Surgical debridement with adjunctive antimicrobials achieved a decrease in MMP-8 at three months. Adjunctive use of Emdogain^™ (EMD) was associated with a reduction in 40 PICF proteins compared to access flap surgery alone. Surgical interventions were more effective at reducing probing pocket depth and bleeding on probing both in the short- and long-term. Surgical treatment in combination with EMD was found to be more effective in resolving inflammation up to twelve months.

Background: Periodontitis is a chronic inflammatory disease associated with a dysbiotic biofilm. Many pathogens have been related with its progression and severity, one of which is Aggregatibacter actinomycetemcomitans, a Gram-negative bacteria with seven serotypes (a–g) according with the structure of its LPS, with serotype b defined as the most virulent compared with the other serotypes. The aim of this study was to evaluate the response of oral keratinocytes and macrophages to A. actinomycetemcomitans. Methods: Oral keratinocytes (OKF6/TERT2) and macrophages (THP-1) were infected with A. actinomycetemcomitans serotypes a, b and c. The expression of IL-1β, IL-6, IL-8, IL-18, TNF-α, MMP-9, RANKL, TLR-2, TLR-4, TLR-6, thymic stromal lymphopoietin (TSLP), and ICAM-1 was evaluated by qPCR at 2 and 24 h after infection. Results: An increase in the expression of these molecules was induced by all serotypes at both times of infection, with macrophages showing higher levels of expression at 24 h compared to epithelial cells in which the highest levels were observed in the first hours after infection. Conclusions: Keratinocytes and macrophages contribute to the inflammation in periodontitis from the early stages of infection, producing the first waves of cytokines, acting as the first signal for professional immune cell recruitment and modulation of more specific immune responses.

Background: The oral microbiome changes across the lifespan and is modulated by behavioral and metabolic exposures. Tobacco consumption, suboptimal hygiene, and frequent sugar intake disrupt microbial homeostasis, thereby increasing vulnerability to chronic oral diseases. While diet influences systemic metabolic and inflammatory health, evidence describing persistent, direct ecological effects on oral microbial communities remains limited. Objective: The objective of this study is to synthesize mechanistic insights on how dietary patterns shape the oral microbiome and influence systemic inflammatory or metabolic risk. Methodology: A narrative, non-systematic review was conducted through expansive literature exploration. Peer-reviewed original and clinical studies reporting defined dietary exposures caloric restriction, plant-based diets, inorganic nitrate and fiber intake, and high-fat or high-sugar processed diets, were qualitatively evaluated for mechanistic relevance. Key findings: Plant-enriched, high-fiber diets, nitrate intake, and caloric restriction were associated with reduced oxidative stress, lower pro-inflammatory cytokines, and greater diversity of commensal taxa, suggesting improved ecological stability. In contrast, processed diets promote metabolic conditions that indirectly remodel the oral habitat, favoring dysbiosis and a niche permissive to periodontitis. Conclusion: The diet–oral microbiome–systemic inflammation axis is bidirectional and clinically relevant. Understanding both direct ecological regulation and indirect metabolic effects is essential to support precision nutrition strategies aimed at maintaining oral microbial balance and systemic inflammatory risk mitigation.

Osteoarthritis is a degenerative disease affecting the TMJ. It is the most common TMJ disorder and shows a higher prevalence in women and older people. TMJ osteoarthritis (TMJ-OA) is characterized by variable degrees of inflammation, destruction of the articular cartilage, and sub-chondral bone resorption. In this context, diverse pro-inflammatory cytokines, chemokines, enzymes, and bone-resorptive associated factors have been considered as possible markers of active TMJ-OA. The molecular balance is determinant not only for initiation and progression, but also for the clinical expression of the disease. Recent advances in the biochemical analysis of synovial fluid from affected patients have provided new insights into the patho-physiology of the TMJ-OA; however, its molecular pathogenesis still remains unclear. Recently, a Th1 and Th17-dominated immune response has been associated with the inflammatory and destructive events characteristic of TMJ-OA and, in particular, the Th17 lymphocyte pathway has a pivotal role in the increased production of RANKL, which is involved in osteoclast activation and subsequent sub-chondral bone resorption. Understanding the TMJ physiology and pathogenesis of the TMJ-OA, together with the key molecular determinants of the TMJ tissue destruction, will enable the development of new chair-side point of care diagnostics and more conservative treatment modalities with minimal complications.

Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium with seven serotypes (a–g) according to the structure of its LPS, has been defined as one of the most important pathogens in the development of a dysbiotic periodontal biofilm and the onset of periodontitis (an inflammatory chronic disease of the tissues around the teeth), where the serotype b is characterized as the most virulent compared with the other serotypes. The aim of this study was to evaluate the expression of the macrophage polarization markers M0, M1, and M2 against A. actinomycetemcomitans. Methods: THP-1 cells were infected with A. actinomycetemcomitans serotypes a, b, and c. The expression of CD11b, CD4, CD14, and CD68 for M0; IL-6, HLA/DRA, and CXCL10 for M21, and IL-10, CD163, fibronectin-1 or FN1, and CCL17 was evaluated by qPCR at 2 and 24 h after infection. Results: An increase in the expression of these molecules was induced by all serotypes at both times of infection, showing higher levels of expression to the M1 panel at 2 and 24 h compared to other markers. Conclusions: A. actinomycetemcomitans has a role in the macrophage polarization to the M1 phenotype in a non-serotype-dependent manner.