Mariano Sanz Alonso

• Shanbhag, Siddharth; Mayol, Magdalena; Domic, Danijel; Bobbili, Madhusudhan Reddy; Grillari, Johannes & Alonso, Mariano Sanz [Show all 7 contributors for this article] (2025). Harnessing the Therapeutic Potential of Cell Secretomes and Extracellular Vesicles for Craniofacial Regenerative Applications. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.70007. Full text in Research Archive Show summary

  Although tissue engineering and cell therapy have been widely investigated as promising regenerative modalities, their clinical translation has partly been limited by a lack of standardization, high costs, and regulatory barriers. Recently, cell-free therapies (CFT) in the form of cell secretomes [conditioned media (CM)] and extracellular vesicles (EVs) have emerged as viable alternatives to cell therapies. However, much of the evidence is based on preclinical studies. This scoping review aimed to summarize the current evidence for using human-derived CFT, with a focus on EVs, for craniofacial regeneration. Based on predefined inclusion criteria and a systematic search covering three electronic databases (MEDLINE, EMBASE, Web of Science), 122 animal studies (n = 27 CM, n = 95 EVs), and 4 clinical studies (n = 2 CM, n = 2 EVs), mostly reporting on bone and periodontal regeneration, were included. The use of oral-derived CFT, particularly from the periodontal ligament, dental pulp, and gingiva, was frequently reported. A wide range of pre-conditioning strategies, dosages, and delivery methods were tested. The preclinical data revealed a clear adjunctive benefit of CFT with biomaterial scaffolds versus scaffolds alone for bone and periodontal regeneration. Limited clinical data based on small patient groups confirmed the safety and feasibility of CFT, although robust evidence for efficacy is lacking. Finally, several issues related to the clinical translation of CFT have been highlighted for future consideration.

• Shanbhag, Siddharth; Stødle, Ida Haukåen; Lie, Stein Atle; Alonso, Mariano Sanz & Verket, Anders (2025). Histological Outcomes of Root Coverage Procedures: A Systematic Review With Meta‐Analysis. Journal of Periodontal Research. ISSN 0022-3484. 61(1), p. 9–29. doi: 10.1111/jre.70043. Full text in Research Archive Show summary

  Objective: To answer the focused PEOS question: In animals or humans with gingival recession defects (P) what are the histological outcomes (O) of different root coverage procedures (RCPs) (E) in preclinical or clinical studies (S)? Methods: Electronic databases (MEDLINE, EMBASE, CENTRAL) were searched for eligible studies reporting histological outcomes of RCPs in large‐animal models or humans. Histomorphometric data from animal studies were summarized as pooled means (PM) for each RCP and compared between different RCPs using effect sizes (ES) based on random‐effects meta‐analyses. Results: Overall, 41 preclinical (32 canine‐, 5 porcine‐, 4 primate‐models) and 43 clinical studies, mostly case reports/series, were included. The most frequently reported RCPs were coronally advanced flaps with or without connective tissue grafts or soft‐tissue substitutes. Biologicals, such as enamel matrix derivatives (EMD) or membranes, were sometimes used as adjuncts in RCPs. In human biopsies, healing following RCPs mostly occurred via the formation of long junctional epithelium (JE) and connective tissue (CT) adhesion. Some degree of periodontal regeneration was reported in half of the studies. In canine studies with experimentally created defects and limited observation times, PM of new bone, cementum, and CT attachment ranged from 0.17 to 0.50, 0.97 to 2.39, and 1.31 to 2.47, respectively. Meta‐analyses revealed significantly greater new cementum with inserting fibers when using biologicals, particularly EMD (ES 0.86–0.92), or membranes (ES 0.87) as adjuncts in RCPs. Conclusion: Healing following RCPs is generally characterized by “repair” (long JE and CT adhesion). Based on animal studies, the adjunctive use of biologicals or membranes in RCPs may enhance periodontal regeneration at least in the short term.

• Herrera, David; Tonetti, Maurizio S.; Chapple, Iain; Kebschull, Moritz; Papapanou, Panos N. & Sculean, Anton [Show all 68 contributors for this article] (2025). Consensus Report of the 20th European Workshop on Periodontology: Contemporary and Emerging Technologies in Periodontal Diagnosis. Journal of Clinical Periodontology. ISSN 0303-6979. 52(S29), p. 33–33. doi: 10.1111/jcpe.14152. Full text in Research Archive Show summary

  ABSTRACT Background This Consensus Workshop dealt with diagnostic methodologies in the context of surveillance, screening, assessment of stage and grade, prognosis, monitoring and prediction of periodontal status. Several elements provided the impetus for the workshop, including the limited quality of available research on diagnostic tests, the rapid development of new technologies, the implementation of the 2018 classification and the declarations of the World Health Organisation on diagnosis and oral health. Aim To update and evaluate the evidence on diagnostic methods, considering recent advances in knowledge and the implementation of the 2018 classification. Methods The European Workshop Committee of the European Federation of Periodontology guided the development of a consensus report after commissioning eight systematic reviews within three working groups. The reviews were discussed during the in‐person consensus meeting involving 70 participants from 21 different countries. Results Working Group 1 discussed innovations in traditional diagnostic approaches, justified manual probing as the reference standard and assessed the value of image‐based methods. Working Group 2 analysed diagnostic tests based on microbial and host biomarkers and genetic diagnostic tests. Working Group 3 covered emerging technologies to be used within dental and non‐dental clinical settings, focusing principally on the impact of questionnaire‐based assessments and artificial intelligence systems (AIS) in interpreting different data modalities. Conclusion Although manual periodontal probing is firmly established as the reference standard, additional approaches based on imaging, biomarkers, host genetics, questionnaires and the development of emerging applied data science methods (e.g., AIS) are increasingly integrated in periodontal diagnostics.

• Maal, Mehrnaz Beheshti; Bueno, Jaime; Koldsland, Odd Carsten; Alonso, Mariano Sanz & Verket, Anders (2025). Oral Hygiene Reinforcement With or Without Repeated Instrumentation in the Treatment of Peri‐Implant Mucositis—A Randomised Controlled Trial. Journal of Clinical Periodontology. ISSN 0303-6979. doi: 10.1111/jcpe.70012. Full text in Research Archive Show summary

  ABSTRACT Aim To assess the efficacy of repeated submarginal mechanical instrumentation, as an adjunct to oral hygiene instruction, in the treatment of peri‐implant mucositis. Material and Methods Patients with peri‐implant mucositis were allocated to a control group receiving oral hygiene instructions only, or a test group with adjunctive repeated ultrasonic instrumentation with a polyetheretherketone tip. Bleeding on probing reduction was the primary outcome. A blinded examiner recorded clinical variables, and intraoral scans were obtained at baseline, 12 weeks and 24 weeks. Results In total, 58 patients were recruited, and 50 completed the study. Clinical parameters improved from baseline in both groups. There were no significant differences in the reduction of the extent nor the severity of bleeding on probing between the control and the test group at the 12‐ and 24‐week follow‐ups, but a significantly higher reduction in the peri‐implant mucosa volume was observed in the test group from 12 to 24 weeks. Conclusions Ultrasonic instrumentation with a polyetheretherketone tip adjunctive to oral hygiene instructions did not render a higher reduction in bleeding on probing or lead to improved clinical outcomes. Still, it resulted in a higher reduction of the peri‐implant mucosa volume as compared to oral hygiene instructions alone.

• Mustafa, Kamal; Yamada, Shuntaro; Sanchez, Nerea; Mayol, Magdalena; Gjerde, Cecilie & Alonso, Mariano Sanz (2025). Cell Therapy for Periodontal, Soft-Tissue, and Craniofacial Regeneration. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.70011. Full text in Research Archive Show summary

  Periodontal and craniofacial regeneration presents significant challenges owing to the complex tissue architecture, inadequate vascularization, and diminished stem cell populations within damaged tissues. Traditionally, autologous bone grafts or alternative bone substitute materials have been employed to address these conditions; however, these approaches are constrained by donor site morbidity, limited availability, and suboptimal regenerative efficacy. The advancement of mesenchymal stem/stromal cell (MSC) biology has accelerated the development of cell-based therapies in modern dentistry, which now focuses on biologically driven approaches to regenerate tissues. MSC-based therapies currently under investigation, both preclinically and clinically, show promise for improving tissue integration and healing processes of both soft and hard tissues, attributable to their multipotent nature, immunomodulatory properties, and paracrine signaling capabilities. Nevertheless, obstacles persist, including inconsistent standardization, limited scalability, regulatory hurdles, a paucity of controlled studies, and restricted biomaterial options. This review evaluates MSC-based treatments for periodontal and craniofacial reconstruction by discussing recent research findings and existing obstacles. This review also examines future prospects, such as advanced biofabrication methods, including 3D printing and bioprinting, which have the potential to improve personalized cell therapy for periodontal and craniofacial regeneration.

• Haugen, Håvard Jostein; Bueno, Jaime; Hussain, Badra; Raquel, Osorio & Alonso, Mariano Sanz (2025). Comparative study of polymeric nanoparticles and traditional agents in dental implant decontamination. Journal of Applied Biomaterials & Functional Materials (JABFM). 23. doi: 10.1177/22808000251313948. Full text in Research Archive Show summary

  Peri-implant diseases, such as peri-implantitis, affect up to 47% of dental implant recipients, primarily due to biofilm formation. Current decontamination methods vary in efficacy, prompting interest in polymeric nanoparticles (NPs) for their antimicrobial and protein-specific cleaning properties. We focused on removing pellicle layers and their ability to resist recontamination, comparing their performance against established decontamination agents. This study evaluated the efficacy of polymeric nanoparticles (NPs) in decontaminating titanium dental implants by removing proteinaceous pellicle layers and resisting recontamination. Titanium discs were treated with saline water, PrefGel®, hydrogen peroxide (H2O2), GUM® Paroex®, or polymeric NPs, and analysed using SEM, EDX, XPS, and contact angle measurements to assess changes in surface composition, morphology, and hydrophilicity. Polymeric NPs significantly reduced nitrogen levels compared to PrefGel® (mean reduction: 2.6%, p < 0.05), indicating effective protein removal. However, their carbon reduction efficacy was similar to that of other agents. SEM images revealed that polymeric NPs disaggregated larger protein aggregates but did not fully decontaminate the surface. Contact angle analysis showed changes in hydrophilicity consistent with other treatments. Hydrogen peroxide performed best overall, achieving the lowest carbon levels post-recontamination (mean reduction: 13%, p < 0.01). While polymeric NPs exhibited unique protein-specific cleaning potential, their overall performance was comparable to traditional agents. Residual contaminants, including carbon and oxygen, persisted on all treated surfaces, indicating enhanced cleaning strategies were needed. These findings highlight the potential of polymeric NPs as an innovative approach to implant decontamination, particularly for protein-specific biofilm control. While polymeric nanoparticles introduce a novel approach to dental implant decontamination, particularly in protein removal, their overall efficacy matches existing methods, although hydrogen peroxide performed better. This research, with its thoroughness and attention to detail, instils confidence in the audience about the reliability of the research findings

• Palombo, David; Rivara, Federico; Nogueira, Liebert Parreiras; Vignoletti, Fabio; Esporrin, Javier Sanz & Haugen, Håvard Jostein [Show all 7 contributors for this article] (2025). Three-Dimensional Hard And Soft Tissue Healing At Implants With A Modified Neck Design: An In Vivo Preclinical Study. Clinical Implant Dentistry and Related Research. ISSN 1523-0899. doi: 10.1111/cid.70065. Full text in Research Archive
• Smedås, Anne Kari; Paris, Lovise Gangeskar; Anam, Niyaz Abdulbaqi Abdulmajid; Kristoffersen, Einar Klæboe; Alonso, Mariano Sanz & Mustafa, Kamal Babikeir Elnour [Show all 8 contributors for this article] (2025). Secretomes of Gingival Fibroblasts From Periodontally Diseased Tissues: A Proteomic Analysis. Clinical and Experimental Dental Research. 11(1). doi: 10.1002/cre2.70103. Full text in Research Archive Show summary

  Objective: Cell secretomes represent a promising strategy for periodontal and bone regeneration. The objective of this study was to characterize the secretome of human gingival fibroblasts (GF) from periodontally diseased tissues (GF-perio) using proteomics. Materials and Methods: Conditioned media of GF-perio from periodontitis patients (n = 6, 48-h serum-free culture) were subjected to liquid chromatography with tandem mass spectrometry. Global profiles, differentially expressed proteins (DEPs), and functional/gene-set enrichment (FEA) were analyzed using bioinformatics. Selected bone regeneration-related proteins were additionally measured using a multiplex immunoassay. Conditioned media of GF from periodontally healthy subjects were used as a reference. Results: Overall, 1833 proteins were detected in GF-perio secretomes, including several growth factors, cytokines, chemokines, and extracellular matrix proteins important for wound healing and regeneration. Key bone-related cytokines (FGF2, MCP1, GPNMB, MMP2, IL6, IL8) were confirmed by an immunoassay. Compared to the reference group, 127 exclusive proteins and 73 DEPs (p < 0.05) were identified in the GF-perio group. FEA revealed significant enrichment of “exosome” and “cytoplasm” related cellular components in GF-perio secretomes. Conclusion: The secretome of GF from periodontally diseased tissues may hold therapeutic potential, with several proteins important for wound healing and regeneration, especially those related to exosome functions.

• Papageorgiou, Spyridon N.; Antonoglou, Georgios N.; Eliades, Theodore; Martin, Conchita & Alonso, Mariano Sanz (2024). Orthodontic treatment of patients with severe (stage IV) periodontitis. Seminars in orthodontics. ISSN 1073-8746. p. 1–12. doi: 10.1053/j.sodo.2024.01.004. Full text in Research Archive
• Bueno, Jaime; Martinez, Maria; Ambrosio, Nagore; Rosal, Juan del; Robledo-Montaña, Javier & Gamonal, Juan D. [Show all 16 contributors for this article] (2024). Comparison of Micro-CT and Morphometric Outcomes in a Modified Experimental Rat Model of Periodontitis. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.13354. Full text in Research Archive Show summary

  Aim To assess the correlation between micro-computed tomography (micro-CT) and linear morphometric measurements in terms of mandibular bone levels in a modified experimental periodontitis model in rodents to study the mechanisms of association between periodontal destruction and neuroinflammation. Methods The proposed in vivo experimental periodontitis model involves the administration of oral rinses with Porphyromonas gingivalis and Fusobacterium nucleatum, four times per week during 4, 8 or 12 weeks, in 24 male Wistar Hannover rats (180 g, 5 weeks old). After euthanasia, hemi-mandibles were collected. One hemi-mandible was analysed using morphometry, while the other was assessed with micro-CT. Linear measurements were taken at the buccal aspect and furcation level for both techniques, and volumetric measurements were also obtained with micro-CT. Passing–Bablok regression analysis was used to compare the results of both techniques, with morphometric measurements serving as the reference. Moreover, Lin's Concordance correlation coefficient was calculated to assess the level of agreement. Periodontal clinical variables with neuroinflammatory parameters from the frontal cortex were used to evaluate the association between the resulting condition and neuroinflammation. Results Twenty-one out of the initial 24 rats were analysed. The micro-CT linear measurements demonstrated high concordance values with the linear morphometric measurements at the buccal surfaces of the roots in molars (r = 0.714) but not at the furcation area (r = 0.052). At 12 weeks, there was a significant impact on neuroinflammation with significant decreases in iNOS levels and p-mTOR levels at 4 and 8 weeks. Conclusion The proposed in vivo experimental periodontitis model demonstrated a high degree of correlation between morphometric and micro-CT measurements in buccal areas but not at the furcation level. Concomitantly, there was a significant temporary modulation of the neuroinflammatory response.

• Shanbhag, Siddharth; Al-Sharabi, Niyaz Abdulbaqi Abdulmajid; Fritz-Wallace, Katarina; Kristoffersen, Einar Klæboe; Bunæs, Dagmar Fosså & Mario, Romandini [Show all 9 contributors for this article] (2024). Proteomic Analysis of Human Serum Proteins Adsorbed onto Collagen Barrier Membranes. Journal of Functional Biomaterials. 15(10). doi: 10.3390/jfb15100302. Full text in Research Archive Show summary

  Collagen barrier membranes are frequently used in guided tissue and bone regeneration. The aim of this study was to analyze the signature of human serum proteins adsorbed onto collagen membranes using a novel protein extraction method combined with mass spectrometry. Native porcine-derived collagen membranes (Geistlich Bio-Gide®, Wolhusen, Switzerland) were exposed to pooled human serum in vitro and, after thorough washing, subjected to protein extraction either in conjunction with protein enrichment or via a conventional surfactant-based method. The extracted proteins were analyzed via liquid chromatography with tandem mass spectrometry. Bioinformatic analysis of global profiling, gene ontology, and functional enrichment of the identified proteins was performed. Overall, a total of 326 adsorbed serum proteins were identified. The enrichment and conventional methods yielded similar numbers of total (315 vs. 309), exclusive (17 vs. 11), and major bone-related proteins (18 vs. 14). Most of the adsorbed proteins (n = 298) were common to both extraction groups and included several growth factors, extracellular matrix (ECM) proteins, cell adhesion molecules, and angiogenesis mediators involved in bone regeneration. Functional analyses revealed significant enrichment of ECM, exosomes, immune response, and cell growth components. Key proteins [transforming growth factor-beta 1 (TGFβ1), insulin-like growth factor binding proteins (IGFBP-5, -6, -7)] were exclusively detected with the enrichment-based method. In summary, native collagen membranes exhibited a high protein adsorption capacity in vitro. While both extraction methods were effective, the enrichment-based method showed distinct advantages in detecting specific bone-related proteins. Therefore, the use of multiple extraction methods is advisable in studies investigating protein adsorption on biomaterials.

• Shanbhag, Siddharth; Sanz-Esporrin, Javier; Kampleitner, Carina; Lie, Stein Atle; Mustafa, Kamal & Gruber, Reinhard [Show all 7 contributors for this article] (2024). Peri-implant bone regeneration in pigs. International Journal of Implant Dentistry. doi: 10.1186/s40729-024-00572-9. Full text in Research Archive Show summary

  Purpose To review the current literature to answer the focused question: in the experimental pig model (population), which types of peri-implant bone defects (exposure) have been used evaluate different modes of therapy and what is their capacity for spontaneous healing and regeneration (outcome)? Methods Following PRISMA guidelines, electronic databases were searched for studies reporting peri-implant bone defects in the maxillae or mandibles of pigs. Those studies which reported a control group of untreated defects with assessment of spontaneous regeneration [new bone area (BA)] and/or re-osseointegration [new bone-to-implant contact (BIC)] via quantitative radiography or histomorphometry were included in a random effects meta-analysis for the outcomes BA and BIC. Results Overall, 21 studies, mostly performed in the mandibles of minipigs, were included. Most studies reported ‘acute’ intrabony (circumferential and/or dehiscence; n = 12) or supra-alveolar defects (horizontal; n = 4). Five studies attempted to induce ‘chronic’ peri-implantitis lesions using ligatures with conflicting results. Meta-analyses revealed pooled estimates (with 95% confidence intervals) of 48.07% BIC (30.14–66%) and 64.31% BA (42.71–85.91%) in intrabony defects, and 52.09% BIC (41.83–62.35%) and 28.62% BA (12.97–44.28%) in supra-alveolar defects. Heterogeneity in the meta-analysis was high (I2 > 90%). Conclusion Current evidence for peri-implant bone regeneration in pigs is mainly based on acute intrabony defects, which demonstrate a high capacity for spontaneous regeneration and re-osseointegration. The evidence for chronic peri-implantitis is limited and does not clearly indicate a spontaneous progression of the disease in this animal model.

• Khan, Sadia Nazir; Ribeiro-Vidal, Honorato; Virto, Leire; Bravo, Enrique; Nuevo, Paula & Koldsland, Odd Carsten [Show all 8 contributors for this article] (2024). The Decontamination Effect of an Oscillating Chitosan Brush Compared With an Ultrasonic PEEK-Tip: An In Vitro Study Using a Dynamic Biofilm Model. Clinical Oral Implants Research. ISSN 0905-7161. doi: 10.1111/clr.14360. Full text in Research Archive
• Hussain, Badra; Grytten, Jostein Ivar; Rongen, Gunnar; Alonso, Mariano Sanz & Haugen, Håvard Jostein (2024). Surface Topography Has Less Influence on Peri-Implantitis than Patient Factors: A Comparative Clinical Study of Two Dental Implant Systems. ACS Biomaterials Science and Engineering. 10(7), p. 4562–4574. doi: 10.1021/acsbiomaterials.3c01809. Full text in Research Archive Show summary

  Objectives: This study aims to assess the risk of peri-implantitis (PI) onset among different implant systems and evaluate the severity of the disease from a population of patients treated in a university clinic. Furthermore, this study intends to thoroughly examine the surface properties of the implant systems that have been identified and investigated. Material and methods: Data from a total of six hundred and 14 patients were extracted from the Institute of Clinical Dentistry, Dental Faculty, University of Oslo. Subject- and implant-based variables were collected, including the type of implant, date of implant installation, medical records, recall appointments up to 2022, periodontal measurements, information on diabetes, smoking status, sex, and age. The outcome of interest was the diagnosis of PI, defined as the occurrence of bleeding on probing (BoP), peri-implant probing depth (PD) ≥ 5 mm, and bone loss (BL). Data were analyzed using multivariate linear and logistic regression. Scanning electron microscopy, light laser profilometer, and X-ray photoelectron spectroscopy were utilized for surface and chemical analyses. Results: Among the patients evaluated, 6.8% were diagnosed with PI. A comparison was made between two different implant systems: Dentsply Sirona, OsseospeedTM and Straumann SLActive, with mean follow-up times of 3.84 years (SE: 0.15) and 3.34 years (SE: 0.15), respectively. The surfaces have different topographies and surface chemistry. However, no significant association was found between PI and implant surface/system, including no difference in the onset or severity of the disease. Nonetheless, plaque control was associated with an increased risk of developing PI, along with the gender of the patient. Furthermore, patients suffering from PI exhibited increased BL in the anterior region. Conclusion: No differences were observed among the evaluated implant systems, although the surfaces have different topography and chemistry. Factors that affected the risk of developing PI were plaque index and male gender. The severity of BL in patients with PI was more pronounced in the anterior region. Consequently, our findings show that success in implantology is less contingent on selecting implant systems and more on a better understanding of patient-specific risk factors, as well as on implementing biomaterials that can more effectively debride dental implants.

• Carvalho, Érika B. S.; Romandini, Mario; Sadilina, Sofya; Sant'Ana, Adriana C. P. & Alonso, Mariano Sanz (2023). Microbiota associated with peri-implantitis—A systematic review with meta-analyses. Clinical Oral Implants Research. ISSN 0905-7161. doi: 10.1111/clr.14153. Full text in Research Archive Show summary

  Abstract Aim To answer the following PECO question: “In systemically healthy human subjects (P), which are the differences between peri‐implantitis (E) and peri‐implant health/mucositis (C) in terms of bacterial presence/count (O)?” Materials and Methods Cross‐sectional studies fulfilling specific inclusion criteria established to answer the PECO question were included. Two review authors independently searched for studies, screened the titles and abstracts, did full‐text analysis, extracted the data from the included reports, and performed the risk of bias assessment through an adaptation of the Newcastle/Ottawa tool for cross‐sectional studies and of the JBI critical appraisal checklist. In case of disagreement, a third reviewer author took the final decision. Study results were summarized using random effects meta‐analyses. Results A total of 12 studies were included, involving 1233 participants and 1513 implants. Peri‐implantitis was associated with the presence of S . epidermidis (Odds ratio, OR = 10.28 [95% Confidence interval, CI: 1.26–83.98]), F .  nucleatum (OR = 7.83 [95% CI: 2.24–27.36]), T .  denticola (OR = 6.11 [95% CI: 2.72–13.76]), T .  forsythia (OR = 4.25 [95% CI: 1.71–10.57]), P .  intermedia (OR = 3.79 [95% CI: 1.07–13.35]), and P .  gingivalis (OR = 2.46 [95% CI: 1.21–5.00]). Conversely, the presence of A .  actinomycetemcomitans (OR = 3.82 [95% CI: 0.59–24.68]), S .  aureus (OR = 1.05 [95% CI: 0.06–17.08]), and C .  rectus (OR = 1.48 [95% CI: 0.69–3.17]) was not associated with peri‐implantitis. Conclusions Peri‐implantitis is associated with the presence of S .  epidermidis and specific periodontopathogens ( P .  gingivalis , T .  forsythia , T .  denticola , F .  nucleatum , and P .  intermedia ). (CRD42021254589)

• Baima, Giacomo; Minoli, Margherita; Michaud, Dominique S.; Aimetti, Mario; Alonso, Mariano Sanz & Loos, Bruno G. [Show all 7 contributors for this article] (2023). Periodontitis and risk of cancer: Mechanistic evidence. Periodontology 2000. ISSN 0906-6713. doi: 10.1111/prd.12540. Full text in Research Archive Show summary

  Abstract This review aims to critically analyze the pathways of interaction and the pathogenic mechanisms linking periodontitis and oral bacteria with the initiation/progression of cancer at different body compartments. A higher risk of head and neck cancer has been consistently associated with periodontitis. This relationship has been explained by the local promotion of dysbiosis, chronic inflammation, immune evasion, and direct (epi)genetic damage to epithelial cells by periodontal pathobionts and their toxins. Epidemiological reports have also studied a possible link between periodontitis and the incidence of other malignancies at distant sites, such as lung, breast, prostate, and digestive tract cancers. Mechanistically, different pathways have been involved, including the induction of a chronic systemic inflammatory state and the spreading of oral pathobionts with carcinogenic potential. Indeed, periodontitis may promote low‐grade systemic inflammation and phenotypic changes in the mononuclear cells, leading to the release of free radicals and cytokines, as well as extracellular matrix degradation, which are all mechanisms involved in carcinogenic and metastatic processes. Moreover, the transient hematogenous spill out or micro‐aspiration/swallowing of periodontal bacteria and their virulence factors (i.e., lipopolysaccharides, fimbriae), may lead to non‐indigenous bacterial colonization of multiple microenvironments. These events may in turn replenish the tumor‐associated microbiome and thus influence the molecular hallmarks of cancer. Particularly, specific strains of oral pathobionts (e.g., Porphyromonas gingivalis and Fusobacterium nucleatum ) may translocate through the hematogenous and enteral routes, being implicated in esophageal, gastric, pancreatic, and colorectal tumorigenesis through the modulation of the gastrointestinal antitumor immune system (i.e., tumor‐infiltrating T cells) and the increased expression of pro‐inflammatory/oncogenic genes. Ultimately, the potential influence of common risk factors, relevant comorbidities, and upstream drivers, such as gerovulnerability to multiple diseases, in explaining the relationship cannot be disregarded. The evidence analyzed here emphasizes the possible relevance of periodontitis in cancer initiation/progression and stimulates future research endeavors.

• Romandini, Pierluigi; Marruganti, Crystal; Romandini, William Giuseppe; Alonso, Mariano Sanz; Grandini, Simone & Romandini, Mario (2023). Are periodontitis and dental caries associated? A systematic review with meta-analyses. Journal of Clinical Periodontology. ISSN 0303-6979. doi: 10.1111/jcpe.13910. Full text in Research Archive Show summary

  Abstract Aim The epidemiological relationship between periodontitis and caries remains controversial, and evidence synthesis is currently lacking. Therefore, this systematic review was designed to answer the following PECO question: ‘In human adults (P), do subjects suffering from periodontitis (E) have higher presence/number of untreated carious lesions and caries experience (O) than subjects not suffering from periodontitis (C)?’. Materials and Methods Observational studies that met specific inclusion criteria established to answer to the PECO question were included. Two review authors independently searched for eligible studies, screened the titles and abstracts, carried out the full text analysis, extracted the data and performed the risk of bias assessment. In case of disagreement, a third review author took the final decision during ad hoc consensus meetings. Data synthesis was carried out through random‐effects meta‐analyses. Results A total of 18 studies on 21 cohorts, involving 135,018 participants, were included. Meta‐analyses showed a significant association between periodontitis and the presence of at least one tooth with either untreated carious lesions (odds ratio [OR] = 1.63; 95% confidence interval [CI]: 1.32–2.01; p  &lt;.00; I 2  = 83.0%) or caries experience (decayed and filled teeth ≥ 1) (OR = 1.27; 95% CI: 1.01–1.59; p  = .038; I 2  = 90.0%). Moreover, subjects with periodontitis exhibited a higher number of surfaces (difference in means [MD] = 0.86; 95% CI: 0.46–1.27; p  &lt;.001; I 2  = 0.0%) and teeth (MD = 0.35; 95% CI: 0.28–0.42; p  &lt;.001; I 2  = 69.6%) with untreated carious lesions, as well as a higher number of teeth with caries experience (standardized difference in means  [SMD] = 1.46; 95% CI: 0.15–2.78; p  = .029; I 2  = 98.9%) compared with those without periodontitis. Sensitivity analyses focusing on severe periodontitis as exposure mostly showed consistent results. Estimates for caries experience were only slightly attenuated in adjusted models compared with crude models. Subgroup analyses by caries location also indicated that periodontitis was associated only with root caries, while it was not with caries affecting the anatomical crown. Conclusions Periodontitis was found to be associated with the presence and number of treated/untreated root carious lesions. Therefore, caries‐specific preventive measures (e.g., fluorides) should be considered for individuals with periodontitis.

• Strauss, Franz Josef; Marruganti, Crystal; Romandini, Mario; Cavalla, Franco; Neira, Patricio & Jiménez, Francisco J. [Show all 9 contributors for this article] (2023). Epidemiology of mid-buccal gingival recessions according to the 2018 Classification System in South America: Results from two population-based studies. Journal of Clinical Periodontology. ISSN 0303-6979. doi: 10.1111/jcpe.13847. Full text in Research Archive Show summary

  Abstract Aim The aim of this investigation was to estimate the prevalence, severity and extent of mid‐buccal gingival recessions (GRs; classified according to the 2018 Classification System) and to identify their risk indicators in the South American population. Materials and Methods Epidemiological data from two cross‐sectional studies—performed on 1070 South American adolescents and 1456 Chilean adults—were obtained. All participants received a full‐mouth periodontal examination by calibrated examiners. GR prevalence was defined as the presence of at least one mid‐buccal GR ≥ 1 mm. GRs were also categorized into different recession types (RTs) according to the 2018 World Workshop Classification System. Analyses for RT risk indicators were also performed. All analyses were carried out at the participant level. Results The prevalence of mid‐buccal GRs was 14.1% in South American adolescents and 90.9% in Chilean adults. In South American adolescents, the prevalence of RTs was 4.3% for RT1 GRs, 10.7% for RT2 GRs and 1.7% for RT3 GRs. In Chilean adults, the prevalence of RT1 GRs was 0.3%, while the prevalence of RT2 and RT3 GRs was 85.8% and 77.4%, respectively. Full‐Mouth Bleeding Score (FMBS; &lt;25%) was associated with the presence of RT1 GRs in adolescents. The risk indicators for RT2/RT3 GRs mainly overlapped with those for periodontitis. Conclusions Mid‐buccal GRs affected 14.1% of South American adolescents, whereas they affected most of the Chilean adult population (&gt;90%). While RT1 GRs are more commonly observed in a non‐representative cohort of South American adolescents (when compared to Chilean adults), the majority of Chilean adults exhibit RT2/RT3 GRs.

• Thieu, Minh Khai Le; Stoetzel, Sabine; Rahmati, Maryam; Khassawna, Thaqif El; Verket, Anders & Sanz-Esporrin, Javier [Show all 9 contributors for this article] (2022). Immunohistochemical comparison of lateral bone augmentation using a synthetic TiO<inf>2</inf> block or a xenogeneic graft in chronic alveolar defects. Clinical Implant Dentistry and Related Research. ISSN 1523-0899. doi: 10.1111/cid.13143. Full text in Research Archive Show summary

  Objectives To evaluate osteogenic markers and alveolar ridge profile changes in guided bone regeneration (GBR) of chronic non-contained bone defects using a non-resorbable TiO2 block. Material and methods Three buccal bone defects were created in each hemimandible of eight beagle dogs and allowed to heal for 8 weeks before GBR. Treatment was assigned by block randomisation: TiO2 block: TiO2-scaffold and a collagen membrane, DBBM particulates: Deproteinised bovine bone mineral (DBBM) and a collagen membrane, Empty control: Only collagen membrane. Bone regeneration was assessed on two different healing timepoints: early (4 weeks) and late healing (12 weeks) using several immunohistochemistry markers including alpha smooth muscle actin (α-SMA), osteopontin, osteocalcin, tartrate-resistant acid phosphatase and collagen type I. Histomorphometry was performed on Movat Pentachrome and Von Kossa/Van Gieson stained sections. Stereolithographic models were used to compare alveolar profile changes. Results The percentage of α-SMA and osteopontin increased in TiO2 group after 12 weeks of healing at the bone-scaffold interface, while collagen type I increased in the empty control group. In the defect area, α-SMA decreased in the empty control group, while collagen type I increased in the DBBM group. All groups maintained alveolar profile from 4 to 12 weeks, but TiO2 group demonstrated the widest soft tissue contour profile. Conclusions The present findings suggested contact osteogenesis when GBR is performed with a TiO2 block or DBBM particulates. The increase in osteopontin indicated a potential for bone formation beyond 12 weeks. The alveolar profile data indicated a sustained lateral increase in lateral bone augmentation using a TiO2 block and a collagen membrane, as compared to DBBM and a collagen membrane or a collagen membrane alone.

• Hussain, Badra; Haugen, Håvard Jostein; Aass, Anne Merete; Alonso, Mariano Sanz; Antonoglou, Georgios & Bouchard, Philippe [Show all 23 contributors for this article] (2021). Peri-Implant Health and the Knowing-Doing Gap—A Digital Survey on Procedures and Therapies. Frontiers in Dental Medicine. 2(726607). doi: 10.3389/fdmed.2021.726607. Full text in Research Archive Show summary

  Objectives: Peri-implant tissue maintenance and treatment is becoming a serious challenge in implantology. With increasing numbers of implants being placed, more cases of peri-implant mucositis and peri-implantitis is seen. A digital survey on peri-implant disease management was issued to experts in periodontology and implantology to identify the tools and procedures most commonly used today to treat peri-implant diseases and successfully manage peri-implant health. The primary aim was to assess whether there is consensus in the choice of treatment to manage peri-implant diseases and to prevent their recurrence once treated. The secondary aim was to obtain insight into future protocols and /or devices, and the research and development needed. Materials and Methods: Participants in this digital survey were professionals specialising in periodontology, oral surgery, and implant dentistry. The questionnaire included both a series of closed- and open-ended questions. A total of 16 countries participated. The survey was sent by e-mail to 70 individuals, 66 received the survey and 37 of receivers responded, two of the participants were excluded due to insufficient filling of the survey. In the end 35 respondents completed the survey. Results: Respondents agree that the efficacy of mechanical and chemical decontamination of implant surfaces needs to be improved and better documented. It is a common opinion that the current remedies, mostly adapted from periodontal practises, do not provide effective and reliable clinical outcomes when treating peri-implant ailments. There is a general agreement amongst experts that regularly scheduled (3–6-month intervals) maintenance treatments are essential for maintaining peri-implant health in patients experiencing implant complications. Respondents are also concerned about unnecessary use of systemic antibiotics for managing peri-implant health. Conclusion: Regardless of agreements in parts, there was no observed consensus on the most effective treatment options for treating peri-implantitis. The experts all agree it is an urgent need for well-designed, long-term follow-up randomised and controlled clinical trials comparing interventions to provide an evidence-based strategy for peri-implant health management.

• Virto, Leire; Cano, Pilar; Jiménez-ortega, Vanesa; Fernández-mateos, Pilar; González, Jerián & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2018). Melatonin as adjunctive therapy in the treatment of periodontitis associated with obesity. Journal of Clinical Periodontology. ISSN 0303-6979. 45(11), p. 1336–1346. doi: 10.1111/jcpe.13013. Full text in Research Archive Show summary

  Aims To study the effect of adjunctive systemic administration of melatonin to standard mechanical periodontal therapy in obese rats with experimental periodontitis. Materials and methods In 42 Wistar rats with an initial body weight of 180 g., half (n=21) were fed with a high‐fat diet to induce obesity. In both obese and normal‐weight groups, experimental periodontitis was subsequently induced through oral gavages with a combination of Porphyromona gingivalis and Fusobacterium nucleatum. Both groups were randomly allocated to either, no treatment or periodontal treatment consisting on standard mechanical debridement, with either adjunctive chlorhexidine or melatonin. Outcomes were evaluated by the changes in clinical parameters (probing depth modified gingival index, plaque dental index and bleeding on probing), in bone resorption and in the levels of biomarkers in plasma and in gingival tissue (inflammatory cytokines, insulin, leptin, osteocalcin, osteopontin, plasminogen activator inhibitor‐1, intercellular adhesion molecule 1, E‐selectin and lipids). Results In the obese‐periodontitis group, adjunctive melatonin administration resulted in reduced gingival inflammation and bleeding on probing, with significant reductions in probing depth and enhanced bone repair demonstrated by Micro‐CT (15% reduction in alveolar bone destruction) when compared with the same group treated with adjunctive CHX or the normal‐weight rats with either melatonin or CHX. In this melatonin‐treated obese‐periodontitis group, a significant impact on biochemical biomarkers was also demonstrated in both gingival and plasma samples, when compared with the other groups, with significant reductions in pro‐inflammatory cytokines. Conclusions Adjunctive melatonin therapy significantly reduced alveolar bone loss and exerted a protective anti‐inflammatory effect mainly in those experimental animals affected by the co‐morbidity of periodontitis and obesity.

• Virto, Leire; Haugen, Håvard Jostein; Fernández-mateos, Pilar; Cano, Pilar; González, Jerián & Jiménez-ortega, Vanesa [Show all 8 contributors for this article] (2018). Melatonin expression in periodontitis and obesity: An experimental in-vivo investigation. Journal of Periodontal Research. ISSN 0022-3484. 53(5), p. 825–831. doi: 10.1111/jre.12571. Full text in Research Archive Show summary

  Background and Objective: Melatonin deficiency has been associated with obesity and systemic inflammation. This study aims to evaluate whether melatonin could interfere with the mechanisms of co-morbidity linking obesity and periodontitis. Material and Methods: Twenty-eight male Wistar rats were randomly divided in 4 groups: control group (Con) (fed with standard diet); high-fat diet group (HFD) (fed with a diet containing 35.2% fat); Con group with induced periodontitis (Con-Perio) and HFD group with induced periodontitis (HFD-Perio). To induce periodontitis, the method of oral gavages with Porphyromonas gingivalis ATCC W83K1 and Fusobacterium nucleatum DMSZ 20482 was used. Circulating melatonin levels were analyzed by multiplex immunoassays. Periodontitis was assessed by alveolar bone loss (microcomputed tomography and histology) and by surrogate inflammatory outcomes (periodontal pocket depth, modified gingival index and plaque dental index). Results: Plasma melatonin levels were significantly decreased (P < .05) in the obese rats with periodontitis when compared with controls or with either obese or periodontitis rats. Alveolar bone loss increased 27.71% (2.28 µm) in HFD-Perio group compared with the Con group. The histological analysis showed marked periodontal tissue destruction with osteoclast activity, particularly in the HFD-Perio group. A significant negative correlation (P < .05) was found between periodontal pocket depth, modified gingival index and circulating melatonin levels. Conclusion: Obese and periodontitis demonstrated significantly lower melatonin concentrations when compared with controls, but in obese rats with periodontitis these concentrations were even significantly lower when compared with either periodontitis or obese rats. These results may indicate that melatonin deficiency could be a key mechanism explaining the co-morbidity effect in the association between obesity and periodontitis.

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• Herrera, David; Alonso, Mariano Sanz & Barkvoll, Pål (2024). Fit for the future: rethinking education in periodontology - European Federation of Periodontology. Full text in Research Archive Show summary

  David Herrera, chair of the European Workshop Committee, Mariano Sanz, co-chair of the Perio Workshop 2023, and ADEE past president Pål Barkvoll explore the consensus outcomes of Perio Workshop 2023 on education in periodontology.

• Haugen, Håvard Jostein; Thieu, Minh Khai Le; Sanz-Esporrin, Javier; Alonso, Mariano Sanz & Verket, Anders (2021). GUIDED BONE REGENERATION OF CHRONIC NON-CONTAINED BONE DEFECTS USING A VOLUME STABLE POROUS TIO2 SCAFFOLD: AN EXPERIMENTAL IN VIVO STUDY. Full text in Research Archive

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