Periodontology 2000[JOURNAL]
Sun
200 papers
Adjunctive antimicrobials and host modulators in nonsurgical periodontal therapy: Focus on patients with diabetes and smokers.
Duarte PM, Lazarin R, Vilela N … +1 more , Feres M
Periodontol 2000 · 2025 Nov · PMID 41239765 · Publisher ↗
Smoking and diabetes mellitus (DM) are major risk factors for periodontitis, often leading to greater disease severity and reduced response to scaling and root planing (SRP). Consequently, adjunctive therapies have been...
Smoking and diabetes mellitus (DM) are major risk factors for periodontitis, often leading to greater disease severity and reduced response to scaling and root planing (SRP). Consequently, adjunctive therapies have been explored to enhance treatment outcomes in these high-risk populations. Given that periodontitis is an infectious-inflammatory disease, both antimicrobial and host-modulating agents have been proposed as adjuncts to support mechanical debridement. This narrative review critically evaluates clinical evidence from randomized clinical trials and systematic reviews assessing the efficacy of these adjuncts in the nonsurgical management of periodontitis in smokers and patients with DM. Local antimicrobials have shown site-specific clinical benefits like probing depth reduction and clinical attachment gain, particularly in deep pockets, although microbiological evidence is limited. Systemic antimicrobials, particularly the amoxicillin-metronidazole combination, demonstrated sustained clinical and microbiological improvements, especially in diabetic patients. Among host-modulating strategies, sub-antimicrobial dose doxycycline and locally delivered statins have shown promising effects, though high-quality, long-term evidence is still lacking. Adjunctive therapies may improve periodontal treatment outcomes in high-risk populations, particularly in cases of severe disease. Nonetheless, significant heterogeneity in study design, outcome assessment, and risk factor control limits the generalizability of current findings. Future research should prioritize rigorous methodology, stratified analyses, and the use of clinically meaningful endpoints to better inform evidence-based decisions on adjunctive therapies in patients with risk factors.
Long-term stability of sinus complication management.
Galindo-Moreno P, Testori T, Padial-Molina M … +3 more , Olaechea A, O'Valle F, Galindo-Fernandez P
Periodontol 2000 · 2025 Nov · PMID 41225708 · Publisher ↗
Maxillary sinus augmentation shows a low incidence of complications and high clinical success due to favorable biological conditions and typically transient issues. Most complications are intraoperative, such as Schneide...
Maxillary sinus augmentation shows a low incidence of complications and high clinical success due to favorable biological conditions and typically transient issues. Most complications are intraoperative, such as Schneiderian membrane perforation or hemorrhage, and are often resolved immediately. Postoperative complications, like sinusitis, graft loss, and voice alterations, are less frequent but clinically relevant. This study evaluates the long-term effects of intraoperative and postoperative complications in maxillary sinus augmentation. A specific classification was used to differentiate these complications, focusing on their impact on bone graft maintenance and dental implant survival. Special attention was given to the progression of sinus inflammatory pathology, from preoperative conditions to acute and chronic sinusitis. While intraoperative complications are generally manageable, they can predispose patients to postoperative issues that affect long-term outcomes. Sinus membrane perforation emerged as a key intraoperative factor linked to later sinusitis, compromising graft integrity and implant stability. The evolution of sinus inflammation significantly influences the long-term success of both graft material and implants. Complications in maxillary sinus augmentation, if not properly managed, can have lasting effects. Careful surgical technique and thorough postoperative monitoring are essential to mitigate risks and ensure long-term success. Recognizing the long-term impact of these complications is crucial for optimizing outcomes in maxillary sinus augmentation.
Functional requirements for guided bone regeneration/guided tissue regeneration membrane design: Progress and challenges.
Zhan H, Shi R, Ni H … +5 more , Li H, Yuan C, Lin K, Sculean A, Miron RJ
Periodontol 2000 · 2025 Nov · PMID 41221631 · Publisher ↗
Guided tissue regeneration (GTR) and guided bone regeneration (GBR) membranes are critical for reconstructing periodontal/bone defects, but existing membranes face limitations in osteogenic potential, antibacterial effic...
Guided tissue regeneration (GTR) and guided bone regeneration (GBR) membranes are critical for reconstructing periodontal/bone defects, but existing membranes face limitations in osteogenic potential, antibacterial efficacy, degradation kinetics, mechanical stability, and immunomodulation within the complex oral microenvironment. This review aims to explore cellular interactions between alveolar bone regenerative cells and GBR/GTR membranes, membrane design strategies based on biological functions, and advancements in material engineering to overcome current clinical challenges. A comprehensive search strategy was implemented across PubMed, Scopus, Web of Science databases, as well as clinical trials registers. Data pertinent to membrane synthetic methodology, biological behavior, tissue regeneration outcomes were retrieved from the original studies. A qualitative assessment was performed. Overall, ideal GBR/GTR membranes must meet several functional requirements: (i) Clinical necessities include biocompatibility, selective permeability for nutrient exchange, and clinical operability. GTR aims to create and maintain a stable isolated space to protect blood clots, thereby enabling blood clots and the newly formed tissue to effectively block the migration of epithelial cells. GBR demands rigid space maintenance to resist mucosal compression in edentulous ridges, with greater emphasis on mechanical stability for large bone defects. Degradation kinetics must align with slower bone formation (3-6 months). (ii) Appropriate surface properties (roughness, morphology, stiffness, wettability, charge) and porosity/pore size are critical for cell behavior. (iii) Membrane-based biological regulation can promote cell adhesion and migration, and balance osteoclastogenesis and osteogenesis. Optimization strategies include incorporating bioactive substances for bone regeneration, immunomodulatory agents for anti-inflammatory responses, and antibacterial additives for clinical performance. GBR/GTR membranes require multifunctional integration of barrier functionality, tailored biodegradation, mechanical robustness, and proactive bioactivity (osteogenic, angiogenic, immunomodulatory, and antibacterial). Future designs must prioritize understanding cell-material interactions to develop membranes that dynamically synchronize with the regenerative microenvironment. This review provides a foundation for developing next-generation membranes that effectively address complex oral microenvironment challenges and significantly improve clinical outcomes in bone defect reconstruction. Optimized membranes will enhance space maintenance, reduce infection rates, mitigate premature degradation, and improve predictability in reconstructing periodontal and alveolar bone defects, ultimately advancing regenerative outcomes in implant dentistry and periodontal surgery.
Antibiotics in the treatment of young patients with molar-incisor pattern periodontitis (C-MIP).
Miguel MMV, Santamaria MP, Casarin RCV … +3 more , Stolf CS, Branco-de-Almeida LS, Shaddox LM
Periodontol 2000 · 2025 Nov · PMID 41185144 · Publisher ↗
Grade C molar-incisor pattern periodontitis (C-MIP) is characterized by an aggressive and rapid loss of tooth-supporting structures, affecting 1st molars incisors. This response seems to be due to an exaggerated host inf...
Grade C molar-incisor pattern periodontitis (C-MIP) is characterized by an aggressive and rapid loss of tooth-supporting structures, affecting 1st molars incisors. This response seems to be due to an exaggerated host inflammatory response triggered by a dysbiotic and specific microbial environment. With higher prevalence in young individuals of lower socioeconomic status and African descendants, or from mixed-race populations, this disease also shows a strong familial aggregation that points to a genetic contribution, not yet fully elucidated. Despite the high focus on 1st molar and incisor permanent dentition with usual onset around puberty, this aggressive attachment bone loss has also been reported in the primary dentition, with some retrospective studies suggesting a possible disease initiation in the prepubertal stages. A. actinomycetemcomitans has been strongly implicated in C-MIP severity and progression, although newer technologies have pointed out some other associated species implicated in this disease. Although several clinical therapies have been proposed to treat C-MIP over time, nonsurgical mechanical treatment with systemic antibiotics (ABX) has shown a positive impact on clinical, immunological, and microbiological outcomes in the short and long term, both in primary and permanent affected dentitions. Despite the limited comparative clinical trials approaching C-MIP, the combination of adjunctive amoxicillin (AMX) and metronidazole (MTZ) with nonsurgical debridement is the most recommended ABX regimen to date. Several bacterial species associated with C-MIP are also reduced following this regimen, along with an increased number of health-associated species and modulation of the inflammatory response, both locally and systemically, associated with clinical parameters of success. Despite the systemic ABX benefits, the authors emphasize the importance of early diagnosis and patients' compliance with frequent maintenance care to sustain successful outcomes. Surgical intervention may also be recommended based on remaining residual pockets, along with residual intrabony defects and furcation involvement. In this review, the authors also highlight a comparison of treatment approaches with generalized forms of the disease in young individuals (C-G) and discuss potential future strategies to understand better, prevent, and successfully treat this aggressive disease.
Relationship between vitamin D deficiency and early implant failure and osseointegration.
Miron RJ, Estrin NE, Paz A … +6 more , Gruber R, Farshidfar N, Zhang Y, Sculean A, Wiedemann TG, Ahmad P
Periodontol 2000 · 2025 Oct · PMID 41163589 · Publisher ↗
BACKGROUND: This systematic review investigated the relationship between pre-operative vitamin D levels and implant osseointegration and implant-related outcomes. It also assessed studies involving vitamin D supplementat...
BACKGROUND: This systematic review investigated the relationship between pre-operative vitamin D levels and implant osseointegration and implant-related outcomes. It also assessed studies involving vitamin D supplementation before implant placement. METHODS: In vivo experimental and clinical studies published up to May 15, 2025, were reviewed. Out of 151 initially identified publications, 43 met the inclusion criteria. RESULTS: In total, 16 animal and 27 human studies were included. Most animal studies investigated vitamin D supplementation before implant placement (nine studies), whereas six studies explored vitamin D coatings on implant surfaces. Animal models included osteoporosis, diabetes mellitus, ultraviolet (UV) light deficiency, chronic kidney disease-induced uremia, and orchiectomy. A positive effect was found for vitamin D on implant osseointegration in 13 of the 16 studies. The human studies comprised three case reports, 10 retrospective studies, three prospective case series, eight prospective controlled trials (2-4 cohorts), and three randomized clinical trials (RCTs). Collectively, 22 of the 27 human studies supported a beneficial association between adequate vitamin D levels and improved implant osseointegration or reduced early implant failure. Vitamin D deficiency was associated with up to a fourfold increase in early implant failures. Pre-surgical supplementation with vitamin D enhanced implant osseointegration, improved bone-implant-contact (BIC), promoted peri-implant bone preservation, and reduced early implant failures, even among high-risk populations (i.e., diabetics). When implant-related parameters such as pocket depths, radiographic marginal bone levels, or implant stability were measured, significantly poorer outcomes were consistently observed in vitamin D-deficient groups. CONCLUSIONS/CLINICAL RELEVANCE: Evidence from both animal and human studies strongly indicates that vitamin D deficiency impairs both new bone formation and BIC. Supplementation, particularly in patients with systemic conditions, may improve implant osseointegration outcomes. Pre-operative screening and correction of vitamin D deficiency are recommended to optimize implant success. Additional well-designed prospective clinical trials and RCTs are needed to further elucidate the extent of the correlation between serum vitamin D deficiency and the risk of implant failure.
Long-term stability of soft tissue augmentative procedures at implant sites.
Tavelli L, Barootchi S, Akhondi S … +4 more , Tseng ES, Garcia-Valenzuela FS, Urban IA, Wang HL
Periodontol 2000 · 2025 Oct · PMID 41147360 · Publisher ↗
BACKGROUND: Peri-implant soft tissue phenotype plays a pivotal role in the long-term success of dental implants, influencing health, esthetic, and patient-reported outcomes. This review explores the long-term stability o...
BACKGROUND: Peri-implant soft tissue phenotype plays a pivotal role in the long-term success of dental implants, influencing health, esthetic, and patient-reported outcomes. This review explores the long-term stability of soft tissue augmentation procedures at implant sites, focusing on keratinized mucosa (KM), mucosal thickness (MT), and supracrestal tissue height (STH), and investigating predictors for the stability of the soft tissue margin over time. MATERIALS AND METHODS: A narrative review aiming at identifying clinical studies reporting on the long-term outcomes of soft tissue augmentation procedures at implant sites was conducted. RESULTS: Robust evidence demonstrates that an inadequate soft tissue phenotype, particularly limited KM and thin MT, is associated with increased inflammation, soft tissue dehiscence, and marginal bone loss. Clinical trials and longitudinal studies show that augmentative procedures, including autogenous free gingival grafts, connective tissue grafts, and soft tissue substitutes, lead to stable outcomes in terms of soft tissue levels, volume, and esthetics. Techniques targeting MT and STH, especially through bilaminar approaches, further enhance long-term peri-implant tissue stability. Additionally, soft tissue augmentation has proven effective for managing peri-implant soft tissue dehiscences and improving papilla height, with the stability of the outcomes reported for up to 10 years. CONCLUSIONS: This review highlights the synergistic role of KM, MT, and STH in supporting peri-implant health, esthetics, and long-term tissue stability, and underscores the need for personalized treatment planning based on peri-implant phenotype. Clinical recommendations for when and how to intervene are provided based on the best available evidence. CLINICAL RELEVANCE: Long-term data support the importance of soft tissue augmentation in ensuring implant success, particularly in esthetically demanding zones and compromised sites.
Missing teeth and all-cause mortality in US adults.
Eke PI, Wei L, Thornton-Evans G … +2 more , Greenlund K, Borgnakke WS
Periodontol 2000 · 2025 Jun · PMID 41126559 · Publisher ↗
This study explored the associations between tooth loss and all-cause mortality among 8710 community-dwelling US adults aged ≥30 years who participated in the National Health and Nutrition Examination Surveys (NHANES) II...
This study explored the associations between tooth loss and all-cause mortality among 8710 community-dwelling US adults aged ≥30 years who participated in the National Health and Nutrition Examination Surveys (NHANES) III in 1988-1994 and subsequently were linked to the 2006 National Center for Health Statistics (NCHS) public-use mortality records. At baseline, 22.3% had all 28 non-third molar teeth, 36.4% were missing 1-5 teeth, 28.0% 6-27 teeth, and 13.3 % all 28 teeth. During 12-18 (mean = 14.2) years, 2,385 participants died with 22.4% of the deceased being edentulous versus 12.7% having 28 teeth. Age-adjusted mortality rate was 29.3 (±0.6)/1000 person-years among the former versus 9.9 (±1.3) among the latter. Age-adjusted mortality was associated with edentulism, with edentate being 2.6 times (HR = 2.58; 95% CI: 1.81-3.69) more likely to have died than fully dentate, though attenuated upon further adjustment to 45% greater risk (HR = 1.45; 95% CI: 1.02-2.05). In contrast, this association between mortality and missing some, but not all teeth, was non-significant upon adjustment for all covariates. In conclusion, edentulism-but not missing <28 teeth-among US adults aged >30 years was statistically significantly associated with all-cause mortality over an average of 14.2 years later.
Empiric or individually targeted antimicrobial therapy. Historical perspective and current state.
Mombelli A, Edwards L, Nibali L
Periodontol 2000 · 2025 Oct · PMID 41123046 · Publisher ↗
BACKGROUND: Current periodontal treatment strategies are primarily informed by population-level data, emphasizing average patient outcomes. Adjunctive antibiotic use-typically amoxicillin combined with metronidazole-is g...
BACKGROUND: Current periodontal treatment strategies are primarily informed by population-level data, emphasizing average patient outcomes. Adjunctive antibiotic use-typically amoxicillin combined with metronidazole-is guided by clinical markers of disease severity and progression risk. However, such broad-spectrum regimens may disrupt the oral and gut microbiota, contributing to antimicrobial resistance. AIM: This chapter evaluates the rationale for empirical versus individualized use of antimicrobial agents in periodontal therapy. MATERIALS AND METHODS: A critical review of existing literature was conducted to assess the clinical efficacy and risks of empirical protocols and to explore the potential of personalized antimicrobial strategies. RESULTS: Evidence from clinical trials does not consistently support superior outcomes with microbiologically or biologically guided antimicrobial therapy. The cost-effectiveness and patient benefit of such testing remain unclear. Nonetheless, variability in pathogenic profiles, microbiome dynamics, individual host responses, and pharmacological factors supports a move toward personalized therapeutic approaches. Advances in personalized medicine-utilizing genetic testing, biomarkers, and machine learning-enable integration of genomic, proteomic, and metabolomic data to inform targeted interventions, potentially improving efficacy and minimizing adverse effects. CLINICAL RELEVANCE: The future of periodontal therapy is likely to integrate population-based evidence with individualized treatment planning. This hybrid model aims to enhance clinical outcomes by combining broad evidence-based guidelines with patient-specific data, reflecting a shift toward precision medicine in clinical practice.
Nitrate metabolism and periodontal health: The roles of nitric oxide in microbial killing and immunoregulation.
Rosier BT, Hajishengallis G, Wink DA … +1 more , Mira A
Periodontol 2000 · 2025 Oct · PMID 41102935 · Publisher ↗
BACKGROUND: Dietary nitrate, primarily sourced from vegetables, is reduced by oral bacteria to nitrite and subsequently to nitric oxide (NO), a molecule with antimicrobial and immunoregulatory properties, as well as vaso...
BACKGROUND: Dietary nitrate, primarily sourced from vegetables, is reduced by oral bacteria to nitrite and subsequently to nitric oxide (NO), a molecule with antimicrobial and immunoregulatory properties, as well as vasodilatory and other cardiometabolic effects. Studies have shown that nitrate supplementation can lower blood pressure, reduce gingival inflammation, and lead to a shift toward microbial eubiosis in the periodontium. However, a paradox arises: nitrate and nitrite-when produced via NO synthase (NOS) activity during chronic inflammation-can serve as biomarkers of periodontitis. AIM: This narrative review aims to (1) examine the molecular mechanisms underlying the health benefits of NO, particularly those stimulated by nitrate-rich vegetable intake; and (2) explore how chronic inflammation can alter the local environment leading to nitrate and nitrite accumulation. MATERIALS AND METHODS: A targeted literature search was conducted in PubMed and Google Scholar to identify articles related to NO, nitrate metabolism, inflammation, and/or periodontitis. RESULTS: Under homeostatic conditions, NO can react with bacterial iron-sulfur clusters, promoting the elimination of sensitive species, and with host soluble guanylyl cyclase (sGC), activating cGMP signaling pathways that suppress inflammation. In contrast, the inflammatory milieu of periodontitis is characterized by elevated levels of reactive oxygen species (ROS) and free heme, both of which act as NO scavengers, thereby diminishing its bioavailability. Importantly, the reaction of NO with ROS generates various reactive nitrogen species (RNS), which differ functionally from NO. These RNS can be converted into nitrate and/or nitrite (e.g., peroxynitrite, ONOO, decomposes into nitrate), contributing to their accumulation. Additionally, oxidative stress promotes NOS uncoupling, converting NOS from a NO-producing to a ROS-producing enzyme. Furthermore, periodontitis is associated with an impaired nitrate-reduction capacity of the oral microbiota, further decreasing NO levels. CLINICAL RELEVANCE: Oxidative stress and reduced NO availability may drive periodontal dysbiosis and contribute to the systemic impact of periodontitis. These disease-related conditions could be mitigated through dietary interventions with nitrate-rich vegetables and adjunctive use of nitrate-reducing probiotics, which warrants further investigation.
Novel and emerging antimicrobial strategies in the management of oral infections.
Unlu O, Yakar N, Kantarci A
Periodontol 2000 · 2025 Oct · PMID 41088717 · Publisher ↗
BACKGROUND: Antibiotics marked a pivotal turning point in human civilization, enhancing social interactions and extending human life expectancy. In addition to their success in treating systemic infectious diseases, they...
BACKGROUND: Antibiotics marked a pivotal turning point in human civilization, enhancing social interactions and extending human life expectancy. In addition to their success in treating systemic infectious diseases, they have significantly improved periodontal treatment outcomes as an adjunct therapy. The current status of systemic antibiotics in periodontal therapy is well established. However, antibiotic-resistant bacteria emerged as a result of their overuse and misuse. It is estimated that by 2050, infections caused by multidrug-resistant bacteria could result in the deaths of 10 million people annually. Beyond promoting the expansion of resistant species, broad-spectrum antimicrobials also eliminate commensal microorganisms and disrupt the microbial balance in distant organs, both of which are essential for maintaining overall health. AIM: This narrative review acknowledges how the use of systemic antibiotics has contributed to our understanding of the role of microbial factors as therapeutic targets, presents novel and emerging technologies that will advance the field, and highlights emerging strategies aimed at eliminating oral disease-related microbial species without inducing antimicrobial resistance or causing dysbiosis in distant parts of the body. MATERIALS AND METHODS: A literature search of the National Library of Medicine (MEDLINE/PubMed) database was conducted to identify publications related to new and developing antimicrobial approaches for treating oral infections without triggering antibiotic resistance or creating dysbiosis in other parts of the body. RESULTS: Previous studies suggest that targeted antimicrobials directed against oral pathobionts and locally effective antibiotics applied at disease sites are potential strategies to reduce the large-scale emergence of antimicrobial resistance and minimize microbiota disruption. Selective action is fundamental to the development of a targeted antimicrobial strategy: An ideal antimicrobial treatment should be highly specific to pathogenic microorganisms without harming the host or its commensal microbiota. In addition to targeted antibiotics and localized drug delivery systems, probiotics, antibodies, phage therapy, photodynamic therapy, and vaccination are promising approaches for addressing the issues associated with broad-spectrum antibiotics. FUTURE DIRECTIONS: The WHO has recommended a global action plan that calls for the development of novel antimicrobials or innovative therapeutic approaches for infectious diseases. New methods are required, extensive education programs should be offered worldwide, and stricter criteria for dental antibiotics should be developed using a comprehensive approach.
Analgesic effects of platelet-rich fibrin (PRF): A systematic review.
Estrin NE, Tran TB, Ahmad P … +4 more , Farshidfar N, Romanos GE, Sculean A, Miron RJ
Periodontol 2000 · 2025 Oct · PMID 41084140 · Publisher ↗
BACKGROUND: Platelet-rich fibrin (PRF), a second-generation autologous platelet concentrate, has gained significant interest for its anti-inflammatory and regenerative characteristics. While its role in tissue healing is...
BACKGROUND: Platelet-rich fibrin (PRF), a second-generation autologous platelet concentrate, has gained significant interest for its anti-inflammatory and regenerative characteristics. While its role in tissue healing is well-recognized, the analgesic potential of PRF remains under-investigated. AIM: The primary objective of this systematic review was to critically evaluate any pain-reported outcome of PRF across all medical and dental procedures in human studies. The secondary objective was to also evaluate outcomes regarding swelling reduction with PRF and other patient-reported outcomes such as quality of life and analgesic consumption in all included studies. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar databases was performed for comparative clinical studies assessing PRF's influence on postoperative pain. Eligible studies included human clinical trials comparing PRF with non-PRF controls, with pain-reported outcomes as the primary outcome. Data on swelling and other patient-reported outcomes, including analgesic use and quality of life, was also evaluated as a secondary objective; however, studies that evaluated these outcomes alone were excluded. A total of 200 comparative clinical studies were included, covering a diverse range of procedures including third molar extractions, palatal wound healing, mucogingival procedures, periodontal/bone procedures, maxillary sinus lifts, endodontic procedures, orthodontic procedures, oral lesions, alveolar osteitis, oroantral communications, medically induced osteonecrosis of the jaw, temporomandibular joint disorders, orthopedic procedures, facial surgery and aesthetics, and other fields of medicine. However, heterogeneity in PRF preparation methods and outcome measures precluded a meta-analysis. RESULTS: Almost all studies reported reduced pain levels in the PRF group compared with non-PRF controls, with additional benefits observed in terms of swelling reduction, decreased analgesic use, and improved patient-reported outcomes. Importantly, it was observed that procedures that tend to generate the most patient-reported pain, such as 3rd molar extractions and autogenous soft tissue grafting from the hard palate, generally reported much lower pain scores following PRF use (72%-85% of studies) and significantly reduced postoperative analgesic use (87.5% of studies). CONCLUSIONS: The autologous nature of PRF, along with the sustained release of bioactive factors, likely plays a vital role in modulating inflammation and promoting tissue healing, hence enhancing patient comfort and recovery. As PRF continues to gain traction in clinical practice, integrating well-designed comparative studies with standardized outcome measures will be necessary to completely understand its therapeutic potential and inform evidence-based guidelines regarding its application.
The efficacy of biologic factors on the surgical therapy of periodontal suprabony defects: A systematic review and network meta-analysis of randomized clinical trials.
Chew C, Donos N, Corbella S … +3 more , Manso I, Castellini G, Calciolari E
Periodontol 2000 · 2025 Sep · PMID 41017124 · Publisher ↗
OBJECTIVES: This systematic review investigated the efficacy of biologic factors in the surgical treatment of periodontal suprabony defects. MATERIALS AND METHODS: Three databases were searched to identify RCTs comparing...
OBJECTIVES: This systematic review investigated the efficacy of biologic factors in the surgical treatment of periodontal suprabony defects. MATERIALS AND METHODS: Three databases were searched to identify RCTs comparing open-flap debridement (OFD) combined with biologic factors only, or combined with bone substitute, and/or barriers to the same intervention without biologics or OFD in terms of probing pocket depth (PPD) reduction, clinical attachment level (CAL) gain, and number of pockets closed. Risk of bias was performed according to RoB 2. Pairwise meta-analyses and frequentist network meta-analyses by using random-effects models were performed. GRADE was employed to assess the certainty of evidence. RESULTS: Ten studies reporting on 253 subjects were included. Overall, adding biologics to OFD leads to a significant improvement in post-treatment PPD and CAL at 9-12 months, with enamel matrix derivative (EMD) having the highest probability of being the best biologic for changes in PPD (-1.91 mm, 95% CI: -3.02, -0.81) and CAL (-2.24 mm, 95% CI: -2.68, -1.79) at a low level of evidence. CONCLUSION: The addition of biologics provides an adjunctive benefit in post-treatment PPD and CAL. However, data should be interpreted with caution due to the heterogeneity of studies, limited data available, risk of bias, and low/moderate evidence.
Use of liquid platelet-rich fibrin (liquid PRF) in temporomandibular joint disorders: A narrative review with clinical recommendations.
Farshidfar N, Amiri MA, Estrin NE … +4 more , Ahmad P, Zhang Y, Sculean A, Miron RJ
Periodontol 2000 · 2025 Sep · PMID 41006956 · Publisher ↗
AIM: This narrative review aimed to gather evidence from comparative and non-comparative clinical studies to assess: (1) whether the administration of liquid platelet-rich fibrin (liquid PRF) provides any clinical benefi...
AIM: This narrative review aimed to gather evidence from comparative and non-comparative clinical studies to assess: (1) whether the administration of liquid platelet-rich fibrin (liquid PRF) provides any clinical benefits for managing temporomandibular disorders (TMD), and if so, based on comparative clinical studies, (2) whether it offers more benefits than no treatment or other treatment modalities, either as a standalone therapy or as an adjunct. MATERIALS AND METHODS: To compile all relevant data, we performed a systematic search of PubMed, Scopus, and Web of Science, supplemented by a Google Scholar search for gray literature and a manual screening of reference lists from eligible studies and relevant reviews, up to April 22, 2025. A total of 23 clinical studies (19 comparative and 4 non-comparative) were ultimately included in this review. RESULTS: Across the included studies, the administration of liquid PRF has been shown to have beneficial effects in reducing pain and enhancing maximum mouth opening (MMO) in patients with TMD. In the majority of studies, the adjunctive use of liquid PRF following arthrocentesis demonstrated greater positive effects compared with arthrocentesis alone. When used adjunctively with arthrocentesis, liquid PRF also showed comparable or superior clinical outcomes in terms of pain reduction and MMO improvement compared with platelet-rich plasma (PRP) and hyaluronic acid (HA). CONCLUSIONS: Based on these findings, the administration of liquid PRF following arthrocentesis appears to be a promising approach for the management of TMD. To support clinical application, this review also presented a step-by-step protocol to guide dental and medical practitioners in the effective use of liquid PRF in patients with TMD. However, further well-designed randomized clinical trials with standardized methodologies are required to strengthen the evidence base and confirm the therapeutic benefits of liquid PRF in the management of TMD due to the high variability among the included studies.
Serum cytokines in periodontal diseases.
Ahmad P, Slots J, Siqueira WL
Periodontol 2000 · 2025 Jun · PMID 40995683 · Full text
Periodontal disease, including gingivitis and periodontitis, is a chronic inflammatory condition that leads to the destruction of the supporting structures of teeth. The disease is characterized by a complex immune respo...
Periodontal disease, including gingivitis and periodontitis, is a chronic inflammatory condition that leads to the destruction of the supporting structures of teeth. The disease is characterized by a complex immune response, where cytokines play a central role in regulating both inflammation and tissue breakdown. Cytokines are small signaling proteins that mediate communication between immune cells, driving the progression of periodontal diseases by activating immune cells, promoting osteoclast differentiation, and stimulating the production of matrix metalloproteinases. This leads to the degradation of periodontal ligament fibers, alveolar bone resorption, and eventual tooth loss. Cytokines contribute not only to localized tissue damage but also to systemic inflammation. Given that periodontal diseases are a chronic inflammatory diseases, their systemic implications are significant. Increasing evidence shows an association between periodontal diseases and other systemic conditions, suggesting that serum cytokine levels could provide valuable insights into both periodontal and systemic health. Understanding the role of serum cytokines in periodontal diseases is critical for identifying systemic inflammatory patterns and disease progression. Evaluating serum cytokine profiles may lead to the discovery of new diagnostic biomarkers and therapeutic targets. Cytokine-modulating therapies could potentially reduce the inflammatory burden in periodontal diseases and improve patient outcomes, especially in individuals with comorbid systemic conditions. This review highlights the current evidence on serum cytokines in periodontal diseases and emphasizes the need for further research to develop cytokine-targeted therapies for improved management of periodontal diseases.
Antibiotic-mediated immune modulation in periodontitis.
Suárez LJ, Arce RM, Furquim CP … +4 more , Gonçalves C, Kantarci A, Feres M, Castro Dos Santos NC
Periodontol 2000 · 2025 Sep · PMID 40944344 · Publisher ↗
Periodontitis is a chronic inflammatory disease affecting the supporting structures of the teeth. Although initiated by dysbiotic microbial communities, its progression is largely driven by the host's uncontrolled inflam...
Periodontitis is a chronic inflammatory disease affecting the supporting structures of the teeth. Although initiated by dysbiotic microbial communities, its progression is largely driven by the host's uncontrolled inflammatory response. While antibiotics have conventionally been employed in periodontitis therapy for their antimicrobial efficacy, emerging evidence suggests that certain antibiotics possess significant immune-modulatory properties independent of their bactericidal or bacteriostatic effects. This review explores the multifaceted immunomodulatory mechanisms by which various classes of antibiotics influence host immune cells and inflammatory pathways relevant to periodontal pathogenesis. Antibiotics were found to influence innate (e.g., pattern recognition receptors, neutrophils, macrophages, epithelial barriers, cytokine production) and acquired immunity (e.g., T and B cells). Additionally, they impact key osteoimmunology components, including interactions between immune and bone cells, the RANKL/osteoprotegerin pathway, and matrix metalloproteinase activity. Understanding the immunomodulatory actions of antibiotics enhances our understanding of their therapeutic potential in managing chronic inflammatory diseases, such as periodontitis. These properties may support inflammation resolution, immune regulation, and tissue repair, offering promising directions for future research and clinical application.
Biological definition of periodontal diseases: A historical review of host-response diagnostics and their implications for disease classification.
Bostanci N, Grant MM, Kebschull M
Periodontol 2000 · 2025 Sep · PMID 40936359 · Publisher ↗
BACKGROUND: Understanding periodontal diseases through a biological lens has been a central aim in periodontal research. Visionary pioneers in the field established the foundations of our knowledge, providing invaluable...
BACKGROUND: Understanding periodontal diseases through a biological lens has been a central aim in periodontal research. Visionary pioneers in the field established the foundations of our knowledge, providing invaluable insights into disease mechanisms and progression. OBJECTIVE: This review highlights the evolving understanding of periodontal diseases, with particular focus on the transition from traditional diagnostic methods to molecular-based approaches. MATERIALS AND METHODS: A narrative review was undertaken through a comprehensive literature search, synthesizing both historical perspectives and contemporary evidence. RESULTS: Over recent decades, fundamental discoveries have significantly advanced our knowledge of periodontal pathogenesis. Despite this, current diagnostic protocols and classification systems remain largely reliant on clinical phenotypes such as pocket depth, attachment loss, and radiographic changes. These measures, while valuable, lack the precision to capture the underlying biological processes. To address this gap, a variety of biological samples (such as saliva, blood, gingival tissue and gingival crevicular fluid) have been explored as potential sources of diagnostic information. Investigations have identified diverse biomarkers, ranging from specific bacterial species and their products to host-derived enzymes, immune mediators, and tissue degradation products originating from the periodontal tissues. These findings colectively underscore the promise of molecular-based strategies to enhance disease detection and monitoring. CONCLUSION: There is growing momentum toward the development of rapid, non-invasive, molecular diagnostic tools for periodontitis. Such approaches could not only enable earlier and more precise diagnosis within dentistry, but may also extend to applications in broader medical and non-dental settings.
Ideal soft tissue graft in periodontal and peri-implant applications: A scoping review.
Yon M, Calciolari E, Mardas N … +2 more , Sculean A, Donos N
Periodontol 2000 · 2025 Sep · PMID 40936322 · Publisher ↗
Soft tissue grafts (STG) are used in a wide range of clinical situations including volume augmentation, keratinized tissue increase, and recession coverage around teeth and implants. Each STG, produced from different sou...
Soft tissue grafts (STG) are used in a wide range of clinical situations including volume augmentation, keratinized tissue increase, and recession coverage around teeth and implants. Each STG, produced from different sources and processed with various techniques, possesses unique material properties and interaction with the host tissues, which ultimately impacts healing and clinical outcome. Certain STG material characteristics may be considered ideal depending on specific clinical requirements, such as mechanical strength, volume stability, and angiogenicity. Hybrid materials and graft engineering may further improve STG properties and provide new graft options. This scoping review evaluates the ideal characteristics of STG in periodontal and peri-implant applications.
Long-term clinical outcomes of periodontal regeneration of intrabony defects: A systematic review and meta-analysis.
Wang HL, Hazrati P, Calatrava J … +2 more , Saleh MS, Alrmali AE
Periodontol 2000 · 2025 Sep · PMID 40931709 · Publisher ↗
This systematic review and meta-analysis aimed to evaluate the long-term clinical outcomes of regenerative procedures compared with access flap surgery for the treatment of intrabony defects, with a minimum follow-up per...
This systematic review and meta-analysis aimed to evaluate the long-term clinical outcomes of regenerative procedures compared with access flap surgery for the treatment of intrabony defects, with a minimum follow-up period of 5 years. A systematic review protocol following PRISMA guidelines was conducted. Both electronic and manual searches were conducted to identify randomized clinical trials (RCTs) on regenerative treatment of deep intrabony defects (≥3 mm) with a follow-up of at least 5 years. Primary outcome variables were probing depth (PD) reduction, clinical attachment level (CAL) gain, recession depth (REC) and tooth loss. Meta-analyses and meta-regressions were performed using random-effects models. Seventeen RCTs published from 2004 to 2022, accounting for 501 defects, with follow-ups ranging from 5 to 20 years, were included. Thirteen studies with some concerns and four with high risks of bias were identified. Meta-analyses revealed that after ≥5 years of follow-up, guided tissue regeneration (GTR) on the intrabony defect resulted in significant CAL gain (3.27 mm; 95% CI: 2.90-3.65) and PD reduction (4.04 mm; 95% CI: 3.69-4.38) compared with baseline. After ≥5 years, regenerative procedures with biologics, bone grafts, or both showed significant improvements in CAL gain (3.21 mm; 95% CI: 2.72-3.70) and PD reduction (3.92 mm; 95% CI: 3.39-4.44). GTR on the intrabony defects obtained higher long-term CAL gain (1.52 mm; 95% CI: 0.06-3.10) and PD reduction (0.89 mm; 95% CI: 0.22-1.99) than OFD (open flap debridement); however, none of the outcomes reached statistical significance (p = 0.06; p = 0.115). Meta-regression identified significant associations between outcomes and factors, such as follow-up time, surgical technique, membrane type, and baseline measurements. The certainty of evidence was low for CAL and PD outcomes, but high for REC. Long-term studies indicate that regenerative procedures for the intrabony defects, particularly GTR, provide significant improvements in clinical parameters compared with baseline. However, the evidence does not conclusively demonstrate the superiority of regenerative approaches over OFD in the long term.
Recent advancements in artificial intelligence-powered cancer prediction from oral microbiome.
Soghli N, Khormali A, Mahboubi D … +2 more , Peng A, Miguez PA
Periodontol 2000 · 2025 Jun · PMID 40931708 · Full text
Oral cancer is a major global health burden, ranking sixth in prevalence, with oral squamous cell carcinoma (OSCC) being the most common type. Importantly, OSCC is often diagnosed at late stages, underscoring the need fo...
Oral cancer is a major global health burden, ranking sixth in prevalence, with oral squamous cell carcinoma (OSCC) being the most common type. Importantly, OSCC is often diagnosed at late stages, underscoring the need for innovative methods for early detection. The oral microbiome, an active microbial community within the oral cavity, holds promise as a biomarker for the prediction and progression of cancer. Emerging computational techniques in the artificial intelligence (AI) field have enabled the analysis of complex microbiome data sets to unravel the association between oral microbiome composition and oral cancer. This review provides a comprehensive overview of learning-based algorithms applied to oral microbiome data for cancer prediction. In particular, this work discusses how typical machine learning (ML) algorithms, such as logistic regression, random forests, and artificial neural networks, identify the unique microbial patterns associated with oral cancer and other malignancies. A search was conducted in Pubmed covering a 10-year period. The goal was to identify previous studies focused on the role of the oral microbiome in oral cancer prediction using AI-powered tools. The search strategy identified 3382 records in total, of which 44 studies met the inclusion criteria. While AI has shown a transformative power in understanding and revealing the oral microbiome's role in cancer studies, its application in clinical settings requires further efforts on standardization of protocols, curation of diverse cohorts, and validation through large-scale multi-centric and longitudinal studies. The integration of AI with oral microbiome analysis holds significant promise for improving early detection, risk stratification, and personalized treatment strategies for OSCC. By identifying unique microbial patterns associated with cancer, AI-driven models offer a noninvasive, cost-effective tool to predict disease progression and guide clinical decision-making. However, translating these advancements into routine clinical practice requires standardized protocols, diverse patient cohorts, and validation through large-scale, longitudinal studies. Once implemented, this approach could transform oral cancer management, enabling timely interventions and improving patient outcomes.
Long-term stability of transcrestal sinus augmentation.
Stuhr SH, Saleh MHA, Testori T … +2 more , Wang HL, Decker AM
Periodontol 2000 · 2025 Sep · PMID 40926615 · Publisher ↗
Transcrestal sinus augmentation has emerged as a minimally invasive alternative to lateral window techniques for vertical bone augmentation in the edentulous maxilla. Since its early introduction and modification over th...
Transcrestal sinus augmentation has emerged as a minimally invasive alternative to lateral window techniques for vertical bone augmentation in the edentulous maxilla. Since its early introduction and modification over the last several decades, this technique has demonstrated predictable outcomes for implant placement in regions with limited bone height. This narrative review examines the current understanding and evolution of transcrestal sinus floor elevation (TSFE), focusing on factors related to long-term stability. We evaluate the procedure's foundational principles, including osteotome-mediated bone condensation and controlled fracture of the sinus floor, which contribute to enhanced primary implant stability. The review addresses critical aspects of treatment planning, surgical execution, and postoperative management while examining potential complications and their resolution. Special attention is given to emerging technologies and materials that may influence treatment outcomes. By synthesizing current evidence and clinical experience, this review aims to provide clinicians with a comprehensive framework for optimizing TSFE procedures and managing potential complications, ultimately working toward a standardized approach through a proposed clinical checklist. Finally, we provide a standardized checklist for TSFE outcome reporting in research studies to facilitate more consistent, reproducible, and comprehensive documentation of surgical procedures, complications, and long-term stability.
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