New Approaches in Etiology, Diagnosis and Treatment of Periodontal Disease

Abstract

Dentistry is under continuous progress. Especially periodontal research and new therapeutic approaches have been developed in the last decades. The mechanism of periodontal disease development, diagnosis, classification system, and treatment protocol are disputed. At the same time, genetics with single-nucleotide polymorphisms (SNPs) signify the role of predisposition in periodontal disease. The relationship between periodontitis and systemic health is considered as an uncontested reality, and comorbidities with other diseases have been proved. Some recent advances and future perspectives in treatment field are immunomodulation, prebiotics, and vaccines, while biomaterials, like emdogain, and minimal invasive surgery are evolved frequently in periodontal treatment. This chapter presents and analyzes the total progress and changes in every aspect of periodontology from the past to now and the future.

1. Introduction

Periodontology is the field of dentistry that concerns the supporting tissues of teeth. In the last years, periodontology has been evolved, and numerous advances are in progress. For example, in the past decades, periodontitis, the infectious disease of gingiva, is considered as a degenerative disease, while now it is proven that it is caused by bacteria. Moreover, the classification system of periodontitis has been modified, based on recent knowledge about progression of the disease, predisposing factors, and state of periodontal destruction.

We conducted a search on the electronic database PubMed, Cochrane, and Scopus up to December 2023. We used as keywords the terms we referred previously.

2. New classification and its application

The previous classification system for periodontal diseases, established in 1999, gave rise to uncertainties and divisions within the dental community. Coupled with the exponential growth of knowledge in recent years, there arose a necessity for a revised classification system that would be more user-friendly, reflective of the latest insights into the etiology and progression of periodontal diseases, and adaptable to evolving clinical practices. To address these needs, a collaborative effort between the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) convened the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions in Chicago from November 9 to 11, 2017, with preliminary discussions commencing in early 2015 [1].

This organizing committee oversaw the creation of 19 review papers and four consensus reports, covering various facets of periodontology and implant dentistry. The task assigned to the authors was twofold: to update the 1999 classification of periodontal diseases and conditions and to formulate a corresponding framework for peri-implant diseases and conditions. Additionally, reviewers and workgroups were tasked with defining relevant case scenarios and establishing diagnostic criteria to aid clinicians in applying the new classification effectively. The outcomes and recommendations of the workshop were reached through consensus agreement among the participants.

Herein, we present a brief overview of the modifications introduced compared to the 1999 classification.

The workshop addressed unresolved issues from the previous classification by delineating between the presence of gingival inflammation at individual sites and the definition of a case of gingivitis. Consensus was reached that bleeding on probing should serve as the primary indicator for setting thresholds for diagnosing gingivitis. Furthermore, the workshop provided clear definitions for periodontal health and gingival inflammation in cases of reduced periodontium following successful periodontal treatment. Specific criteria were established to distinguish between cases of gingival health and inflammation post-treatment, based on bleeding on probing and residual sulcus/pocket depth. This differentiation underscores the importance of comprehensive maintenance and monitoring for patients successfully treated for periodontitis. It was acknowledged that while a patient with gingivitis can revert to a state of health, a patient with periodontitis remains so for life, necessitating lifelong supportive care to prevent disease recurrence. Additionally, the workshop reorganized the classification of non-plaque-induced gingival diseases and conditions based on primary etiology.

Concerning periodontitis, the workshop recognized three identifiable forms: necrotizing periodontitis, periodontitis as a manifestation of systemic disease and the conditions previously categorized as “chronic” or “aggressive” periodontitis, now consolidated under the single category of “periodontitis.” This consolidation was accompanied by the introduction of a multidimensional staging and grading system for periodontitis. Staging primarily considers disease severity at presentation and the complexity of disease management, while grading provides supplementary information regarding the biological features of the disease, including historical disease progression, treatment prognosis, and its potential impact on overall health. Staging comprises four categories (stages 1 through 4), determined by various clinical parameters such as clinical attachment loss, bone loss, probing depth, presence of bony defects, tooth mobility, tooth loss attributed to periodontitis, number of teeth loss, and complication of a case. Grading encompasses three levels (grades A, B, and C) and incorporates factors such as the patient’s general health status, smoking habits or metabolic control in diabetes, as far as disease progression, allowing clinicians to tailor treatment plans accordingly. For a comprehensive understanding of the new classification system for periodontitis, readers are directed to the consensus report and case definition paper on periodontitis.

Furthermore, the revised classification now encompasses systemic diseases and conditions affecting the periodontal supporting tissues. Rare systemic disorders, like Papillon-Lefèvre Syndrome, often present with severe early-onset periodontitis and are classified under “Periodontitis as a Manifestation of Systemic Disease,” categorized by the primary systemic condition. Other systemic conditions, such as neoplastic diseases, may affect the periodontal tissues independent of plaque-induced periodontitis and are classified based on the primary systemic disease under “Systemic Diseases or Conditions Affecting the Periodontal Supporting Tissues.” Common modifiers of periodontitis, like uncontrolled diabetes mellitus, are acknowledged within the new clinical classification as descriptors in the staging and grading process, acknowledging their potential impact on disease progression and treatment outcomes.

The new classification system also introduces revised case definitions for the treatment of gingival recession, incorporating interproximal clinical attachment loss assessments and evaluation of the exposed root and cementoenamel junction. Additionally, a new classification of gingival recession is proposed, integrating clinical parameters such as gingival phenotype and exposed root characteristics. The term “periodontal biotype” has been replaced with “periodontal phenotype” in this context.

Traumatic occlusal force, now referred to as traumatic occlusion, is defined as force exceeding the adaptive capacity of the periodontium and/or teeth, potentially resulting in occlusal trauma, tooth wear. or fracture. While evidence supporting occlusal trauma as a factor in periodontal attachment loss is limited, the terminology has been updated to reflect current understanding.

The section addressing prostheses-related factors has been expanded, with the term “biologic width” replaced by “supracrestal attached tissues.” Additionally, clinical procedures involved in indirect restorations have been included, given emerging evidence suggesting their potential impact on recession and clinical attachment loss.

A new classification for peri-implant health, peri-implant mucositis, and peri-implantitis has been developed, aiming for consensus acceptance worldwide. Peri-implant health is defined both clinically and histologically, characterized by the absence of visual signs of inflammation and bleeding on probing. Peri-implant mucositis, on the other hand, presents with bleeding on probing and visual signs of inflammation, with plaque identified as the primary etiological factor. Peri-implantitis, characterized by inflammation and progressive loss of supporting bone, is assumed to follow peri-implant mucositis and is associated with poor plaque control and a history of severe periodontitis. The onset of peri-implantitis may occur early following implant placement, with evidence suggesting a nonlinear and accelerating disease progression in its absence of treatment.

In conclusion, the updated classification system for periodontal and peri-implant diseases and conditions represents a collaborative effort to incorporate contemporary knowledge and clinical practices. It provides a more comprehensive framework for diagnosis, treatment planning, and monitoring, thereby enhancing patient care and outcomes.

3. Periodontal microflora

Periodontal disease, characterized by inflammation and destruction of periodontal tissues, has long been recognized as a multifactorial condition influenced by microbial, genetic, immunological, and environmental factors. Over time, the understanding of periodontal microbiota has undergone significant evolution, transitioning from a simplistic view centered on individual pathogenic bacteria to a more intricate appreciation of microbial communities and their collective impact within biofilms.

The seminal work of Socransky et al. in 1998 introduced the concept of the “red complex,” comprising Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as a potent periopathogenic complex associated with severe periodontal disease [2]. Furthermore, Actinomyces actinomycetemcomitans, particularly the highly pathogenic JP2 clone, was identified as a significant contributor to aggressive periodontitis, especially in younger individuals [3, 4].

However, recent research has illuminated the intricate interplay between microbial dysbiosis and host response in periodontal disease pathogenesis. The “Inflammation-Mediated Polymicrobial-Emergence and Dysbiotic Exacerbation (IMPEDE)” model has emerged as a novel framework, highlighting the role of dysbiotic plaque biofilms in susceptible hosts in initiating and exacerbating periodontal disease [4].

In addition to the well-known pathogens, several newly identified bacterial species have been implicated in periodontal disease progression [5]. Here are a few recent findings:

Fretibacterium fastidiosum: this is a relatively newly discovered bacterium found in the oral cavity, particularly in individuals with periodontitis. Studies suggest that it may contribute to the progression of periodontal disease by forming biofilms and inducing inflammation [6].

Prevotella histicola: another bacterium associated with periodontitis, Prevotella histicola has been found in higher abundance in patients with periodontal disease compared to healthy individuals. It is believed to be involved in the dysbiosis (microbial imbalance), characteristic of periodontitis [7].

Desulfobulbus oralis: this bacterium has been identified as a potential contributor to periodontal disease. Research suggests that it may play a role in the metabolism of sulfur compounds, which could impact the microbial ecology within periodontal pockets [8].

Prevotella pleuritidis: another member of the Prevotella genus, Prevotella pleuritidis has been found in periodontal pockets of patients with periodontitis. Its specific role in the disease process is still under investigation [9].

In conclusion, the evolution of our understanding of periodontal microflora has shifted the focus from singular pathogenic species to the complex interactions within biofilms and the host immune response. This nuanced perspective emphasizes the importance of considering microbial communities as a whole in periodontal disease etiology and highlights the potential for targeted therapeutic interventions aimed at modulating dysbiosis and mitigating inflammatory processes.

4. Single nucleotide polymorphisms

The hypothesis suggesting the existence of a “high-risk” population group susceptible to periodontitis emerged from seminal clinical research conducted decades ago, which identified varying degrees of disease susceptibility and severity among individuals within the same population [10, 11]. A pivotal study in 1966, examining the primary causes of tooth loss in 1800 patients, revealed a disproportionate number of teeth lost due to periodontitis among a select subset of individuals within each age cohort [12]. This observation was further corroborated by a longitudinal study spanning 28 years, which demonstrated that a small percentage of individuals accounted for a significant majority of total tooth loss during the study period [13].

Chronic periodontitis, the most prevalent form historically, now reclassified into various stages and grades based on severity and risk of progression in the 2018 periodontal disease classification, affects a considerable proportion of adults and typically exhibits a slow progression rate. However, a minority of the population experiences severe forms of periodontitis characterized by rapid tissue destruction, comprising no more than 20% of individuals, constituting the “high-risk group” for the disease. Conversely, most individuals show moderate disease progression, while a small segment exhibits minimal periodontal destruction progression.

In addition to chronic periodontitis, another form known as aggressive periodontitis (now classified as grade C periodontitis) presents with a distinct clinical phenotype characterized by rapid progression and early onset, particularly observed in young, systemically healthy individuals. Within this category, a subgroup known as localized periodontitis grade C, with an incisor-molar pattern, stands out due to its unique clinical presentation, higher prevalence among individuals of African descent, and familial aggregation pattern.

Much of the evidence supporting the role of genetic factors in periodontitis stems from studies focusing on aggressive periodontitis. Observations of increased disease incidence within families, with up to a 50% chance of affected individuals coexisting, underscore the genetic predisposition to this form of the disease. Furthermore, variations in disease prevalence among different racial groups have been noted, with Caucasians exhibiting lower rates compared to individuals of African descent.

Until the early 2000s, investigations into the genetic basis of periodontitis primarily relied on candidate gene approaches, targeting genes implicated in known pathophysiological pathways of the disease. However, this method was limited by the necessity for a priori hypotheses and functional variants in selected genes. As a result, many loci and genes potentially influencing disease susceptibility were overlooked due to limited understanding or involvement in unidentified pathways.

In recent years, genome-wide association studies (GWAS) have revolutionized the study of genetic variants associated with periodontitis. Unlike candidate gene approaches, GWAS offer an unbiased, hypothesis-free approach to screening for disease-associated genetic variants. By simultaneously analyzing millions of single nucleotide polymorphisms (SNPs) across the entire genome, GWAS provide a comprehensive view of genetic contributions to disease susceptibility. SNP, or single nucleotide polymorphism, is a type of genetic variation that occurs within a population. It refers to the variation in a single nucleotide base (A, T, C or G) at a particular position in the DNA sequence among individuals within a species. SNPs are the most common type of genetic variation found in the human genome, with an average occurrence of once every 300 nucleotides. These variations can have an impact on various traits and disease predispositions, which makes them an essential focus of research in genetics, evolutionary biology, and personalized medicine [14].

Modern genetic tools have identified several polymorphisms in genes regulating immune responses and other biological pathways implicated in periodontitis. Among the genes/loci with clear evidence of association with chronic and aggressive periodontitis are Ιl-1b, Il-1a, MMPs COX2, GLT6D1, ANRIL, DEFB1, IL-10, 25(OH)D metabolites, SIGLEC5, DEFA1A3, MTND1P5, and LOC107984137. Importantly, these genetic associations enhance our understanding of periodontal disease pathogenesis and offer potential avenues for innovative risk assessment, outcome prediction, disease management, and treatment strategies [15, 16, 17, 18, 19].

The identification of specific genetic variants associated with periodontitis through GWAS studies offers promising opportunities for translating genetic insights into clinical practice. Incorporating genetic risk assessments into routine periodontal evaluations can enable personalized treatment approaches, including targeted preventive strategies, early intervention for high-risk individuals, and optimized treatment plans tailored to individual genetic profiles. Furthermore, ongoing research in this field holds the potential to develop novel therapeutic interventions aimed at modulating genetic factors implicated in periodontal disease susceptibility, ultimately improving patient outcomes and advancing precision dentistry.

5. Markers of disease activity

Gingival crevicular fluid (GCF) serves as a vital physiological fluid and inflammatory exudate originating from the gingival plexus of blood vessels in the gingival corium, below the epithelium lining of the dentogingival space. Its noninvasive collection from the gingival crevice or periodontal pocket makes it a valuable source for biomarkers associated with periodontal diseases. Collection methods, such as using filter paper or glass capillaries, allow for easy and discomfort-free sampling.

The composition of GCF varies between healthy individuals and those with periodontal diseases, as well as during disease progression. It contains serum-derived components and locally generated biomarkers, offering insights into tissue metabolism, inflammatory cell recruitment, and connective tissue remodeling. GCF reflects the host response to oral microorganisms and the mechanisms by which periodontopathogens exploit these responses for bacterial survival [20].

Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8), along with metalloproteinases like MMP-8 and MMP-9 [21], are key mediators studied in GCF. These cytokines are products of the innate immune response against bacterial pathogens, contributing to tissue destruction. MMPs, particularly MMP-8, MMP-9, and MMP-13, play crucial roles in extracellular matrix degradation and are implicated in periodontal tissue destruction [22].

Moreover, GCF analysis extends to biochemical markers for bone homeostasis, including pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), receptor activator of nuclear factor-kappa β ligand (RANKL), osteoprotegerin (OPG), and osteocalcin. These markers offer insights into future alveolar bone loss prediction and demonstrate significant correlations with clinical parameters and periodontal pathogens.

While single-candidate protein immunoassays have provided valuable insights, they may not offer comprehensive diagnostic support for early periodontal disease. Multiplex protein arrays and mass spectrometry-based proteomics have emerged as promising approaches to characterize the complex network of molecules in GCF. These advanced techniques allow for the identification of novel biomarkers and provide a deeper understanding of disease pathogenesis.

Multiplex protein arrays enable the simultaneous detection and quantification of multiple proteins in GCF, offering a more comprehensive view of the molecular landscape associated with periodontal diseases. This approach allows researchers to examine the interactions between different biomarkers and identify patterns that may be indicative of disease progression or treatment response.

Mass spectrometry-based proteomics offers unparalleled sensitivity and specificity in detecting and quantifying proteins in GCF. By analyzing the entire proteome present in GCF, researchers can uncover novel biomarkers and gain insights into the underlying mechanisms of periodontal diseases [23]. This approach holds great promise for identifying diagnostic and prognostic markers that can aid in personalized treatment strategies.

Overall, proteomic analyses of GCF hold great promise for personalized prevention, diagnosis, and management of periodontal diseases. By complementing clinical examinations, proteomic approaches may enhance our ability to detect and monitor disease activity, ultimately improving patient care outcomes. Continued advancements in proteomic technologies and the exploration of GCF protein profiles offer opportunities for a deeper understanding of periodontal diseases and the development of targeted therapeutic interventions. In the future, integration of proteomic data into clinical practice may enable more precise risk assessment, early detection of disease onset, and personalized treatment planning, leading to improved outcomes for patients with periodontal diseases.

6. Treatment of peri-implantitis

The management of peri-implantitis has evolved alongside advancements in our understanding of peri-implant diseases, with updated guidelines providing comprehensive recommendations for prevention and treatment. Notably, the European Federation of Periodontology (EFP) published a rigorous S3 level Clinical Practice Guideline (CPG) in 2023 [24], following stringent methodological standards set by the Association of Scientific Medical Societies in Germany and utilizing the Grading of Recommendations Assessment, Development, and Evaluation process. This authoritative guideline synthesizes evidence from 13 systematically reviewed studies, evaluates the strength and quality of evidence, and formulates specific recommendations through a consensus process involving leading experts and stakeholders.

These guidelines serve as a pivotal resource for clinicians, healthcare systems, policymakers, and the public, offering evidence-based strategies spanning pre-, peri-, and post-implant phases to mitigate peri-implant diseases. Notably, the focus lies on preventive measures, commencing with primordial prevention strategies aimed at modulating lifestyle and behavioral risk factors, coupled with meticulous surgical and prosthetic planning to preempt the onset of peri-implant mucositis and peri-implantitis.

In the management of peri-implant diseases, the guideline delineates distinct treatment modalities tailored to specific phases and objectives. For instance, in addressing peri-implant mucositis, interventions primarily emphasize effective self-administered oral hygiene and professional mechanical plaque removal (PMPR), while pharmacotherapeutic interventions like photodynamic therapy and systemic/local antibiotics are cautioned against. Furthermore, the guideline highlights the potential benefits of adjunctive oral rinse antiseptics alongside PMPR for a limited duration.

Conversely, the management of peri-implantitis encompasses both non-surgical and surgical interventions, often adopting a stepwise approach. The non-surgical phase aims to control peri-implant biofilms and inflammation through techniques such as sub-marginal instrumentation, supplemented by strategies targeting supramarginal biofilm control and risk factor management. Despite the lack of established endpoints akin to periodontitis treatment, vigilant monitoring and reassessment of outcomes remain integral.

In cases where non-surgical interventions fall short of desired outcomes, surgical intervention becomes imperative. Surgical procedures typically involve flap elevation, removal of inflamed tissue, decontamination of implant surfaces, and, where necessary, reconstructive approaches to manage peri-implant osseous defects. The guideline also underscores the potential role of adjunctive measures such as implant surface decontamination and local/systemic antibiotics.

Overall, the stepwise approach advocated by the guideline underscores the importance of optimizing biofilm and inflammation control before considering more invasive interventions. While further research is warranted to refine treatment protocols and establish definitive endpoints, adherence to evidence-based guidelines ensures the delivery of optimal care and improved outcomes for patients with peri-implant diseases.

In summary, the guidelines established by the European Federation of Periodontology (EFP) offer a comprehensive approach to the prevention and treatment of peri-implant diseases. By integrating the latest research and employing a rigorous methodology, these guidelines provide clinicians with standardized strategies for addressing peri-implant mucositis and peri-implantitis. Key components of these guidelines include primordial prevention strategies targeting lifestyle and behavioral risk factors, as well as meticulous surgical and prosthetic planning to mitigate disease development. Treatment approaches are tailored to specific phases and objectives, with a focus on optimizing biofilm and inflammation control before considering surgical interventions. Looking ahead, the adoption of these guidelines is expected to usher in a new era of precision dentistry, where treatment approaches are personalized based on individual patient needs and risk profiles. By adhering to evidence-based guidelines, clinicians can enhance treatment outcomes and improve the longevity of dental implants, ultimately shaping the future of clinical practice in peri-implant dentistry.

7. Guided dental implant placement

Guided (computed) dental implant surgery was first introduced in late 1990s and since then was evolved due to recent development of digital technology to an easier and more accurate guided dental implant placement, ideal both prosthetically and biologically [25].

Guided dental implant placement has been classified recently into partial or full guidance and the ability to make intraoperative changes before implant placement named either static or dynamic guided implant placement. Recently guided implant surgery has been developed to be applied in a flapless procedure.

Taking into consideration that cone beam computed tomography is a highly accurate and low radiation tomography, the application of flapless guided implant surgery has become very popular. Studies have shown that it has lower morbidity, as it is less invasive, compared to flapped approach. This technique should be limited to cases that do not need bone augmentation and have a wide zone of keratinized tissue. Both flapped and flapless guided implant surgery might show some inaccuracies with respect to the planned implant position.

According to metanalytic measures of dispersions, safety margins should always be applied. A safety margin of 2 mm in depth and 2–3 mm in coronoapical bodily position and 4° angulation should be followed in order to avoid postsurgical implications.

The development and use of navigation systems for dental implant placement has inspired surgeons to investigate the field of robot-assisted implant surgery. Visual, audio, and haptic feedbacks are used in real time to position the implant drill in the correct 3D location. The surgeon could only move the arm which carries the handpiece closer toward the correct position. As the precision of the implant placement is high and allows prefabrication of the prosthesis, most of dental implants can be loaded immediately, if biological factors such as bone quality allow it [26, 27].

Overall, recent advances in dental implant placement technology have made dental implant placement more accurate, with less morbidity and less invasive. These innovations hold promise for improving patient outcomes and expanding the possibilities of implant dentistry.

8. Teeth or dental implants or mesenchymal cells that can grow a tooth

Treatment and long-term preservation of periodontally compromised teeth have always posed significant challenges in dental practice. Moreover, rehabilitating partially or fully edentulous periodontal patients has been notably complex, particularly before the advent of dental implants as a viable treatment option. In cases of advanced periodontal disease, clinicians must meticulously evaluate clinical and radiographic findings alongside tooth and patient-related risk factors [28].

Various publications have proposed different algorithms and criteria for assessing the prognosis of periodontally compromised teeth. For instance, McGuire and Nunn categorized teeth with Class II or III furcation involvement and substantial attachment loss resulting in a poor crown-to-root ratio as ‘questionable’, while designating a tooth as ‘hopeless’ if the remaining clinical attachment level is insufficient to maintain health, comfort, and function, thus necessitating extraction before comprehensive mouth rehabilitation.

Fortunately, the emergence of dental implant dentistry has provided clinicians with a successful and predictable alternative for addressing complete or partial edentulism. The inclusion of dental implants in the treatment of periodontal patients with missing teeth has been well-established, with multiple longitudinal studies demonstrating highly satisfactory results in terms of both survival and success rates. A recent systematic review by Sousa et al. [29] highlighted implant survival rates of 88–98.8% and 92.4–100% over 5–10 years in patients with moderate and advanced periodontal disease, respectively [30].

However, it is crucial to acknowledge the common etiology shared between periodontal and peri-implant diseases, with peri-implantitis and perimucositis being prevalent in patients with a history of periodontal disease. This complicates the rehabilitation of periodontal patients with dental implants, as lesions around implants tend to exhibit a more destructive inflammatory profile and faster progression compared to periodontitis. Furthermore, biofilm removal from implant surfaces can be more challenging due to surface roughness and macro-design, as opposed to dental implant surfaces.

In recent years, medicine has increasingly focused on regenerative approaches employing pluripotent mesenchymal cells. Within dentistry, tissue engineering offers several avenues, including the utilization of stem cells. Specifically, for the regeneration of periodontal tissues, a robust blood supply is essential, as it facilitates the transport of necessary molecules for regeneration. Dental pulp mesenchymal stem cells (DP-MSCs) have shown promise in inducing neoangiogenesis, followed by the formation of a vascular network in the periodontal niche. Additionally, research suggests that DP-MSCs derived from deciduous teeth can differentiate into functional dentin, cementum, and periodontal ligament tissues, including bone.

In conclusion, DP-MSCs hold significant potential for future applications in treating periodontitis and, importantly, for regenerating periodontal tissues without adverse reactions. Continued research and advancements in this area may lead to transformative therapeutic options for managing periodontal disease and enhancing patient outcomes.

9. Probiotics and vaccines

Effective prevention and treatment of the most common oral diseases, including gingivitis, periodontitis, and caries, require collaborative efforts between patients and oral health specialists [31]. While bacterial plaque accumulation in the periodontal environment is a primary driver of periodontal diseases, various host response factors significantly influence disease progression. These factors, encompassing aspects of innate and adaptive immunity, polymorphonuclear neutrophil function, upregulation of pro-inflammatory cytokines, matrix metalloproteinases, and wound healing properties, collectively modulate the progression and severity of periodontal diseases among individuals [32].

In response to the complex interplay of microbial and host factors in periodontal disease pathogenesis, novel approaches targeting inflammation control and immunomodulation have emerged. Probiotics and oral vaccines represent two such innovative strategies for the prevention and treatment of periodontal diseases [33].

Probiotics, defined by the Food and Agricultural Organization/World Health Organization as live microorganisms that, when administered in adequate amounts, confer health benefits to the host and offer promising avenues for periodontal disease prevention [34]. Mechanisms underlying the beneficial effects of probiotics in preventing periodontal disease include the reversal of damage to oral epithelia and mucosa caused by inflammation, modulation of the oral microbiota by competing with dysbiotic microflora for resources, and production of antimicrobial factors that inhibit the proliferation of gram-negative bacteria [33]. While the potential of probiotics to modulate the oral microbiota and exert immune-modulatory effects is promising, further research is needed to identify the most effective probiotic strains for maintaining oral health and to demonstrate their clinical efficacy [35].

Another innovative approach involves the development of oral mucosa-administered vaccines targeting specific pathogens implicated in periodontal disease pathogenesis, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola [32]. These Gram-negative anaerobic bacteria produce virulence factors that stimulate the host immune response, making them ideal vaccine targets. Proposed vaccines include those targeting whole-cell antigens, gingipains, fimbriae, and other virulence factors of periodontal pathogens. While the development of periodontal vaccines holds promise, additional studies are needed to establish their clinical efficacy in human models.

In conclusion, probiotics and oral vaccines represent innovative approaches in the prevention and treatment of periodontal diseases. Continued research efforts are essential to elucidate their mechanisms of action, identify optimal formulations and dosages, and validate their clinical effectiveness. Additionally, ongoing exploration of other novel strategies, such as antimicrobial peptides, host modulation therapy, and personalized medicine, holds promise for further enhancing our ability to combat periodontal diseases effectively in the future.

10. Minimally invasive surgery

In the realm of periodontal therapy, the evolution toward minimally invasive surgical (MIS) techniques marks a significant stride in enhancing treatment precision while prioritizing patient comfort and aesthetic outcomes. These approaches, meticulously crafted to preserve soft tissues and achieve stable primary wound closure, stand as pivotal advancements in modern periodontal care [36].

The integration of operating microscopes and microsurgical instruments has revolutionized surgical precision, offering enhanced visual capacity and refined control over surgical maneuvers while minimizing tissue disruption [37]. The inception of MIS in 1995 heralded a new era in periodontal surgery, with its core tenets centered around minimizing wounds, flap reflection, and trauma to surrounding tissues [38]. Subsequent reports underscore the clinical efficacy of MIS, showcasing improvements in key parameters such as probing pocket depth reduction and clinical attachment level gain [39].

A notable refinement in MIS is the minimally invasive surgical technique (MIST), tailored specifically for treating isolated intra-bony defects with a focus on periodontal regeneration. This technique, integrating established papilla preservation strategies and meticulous suturing, not only reduces surgical trauma but also ensures stable wound closure and enhanced patient comfort [40].

Building upon these foundations, the modified minimally invasive surgical technique (M-MIST) further refines surgical invasiveness by preserving the interdental papilla while raising only a buccal flap, thereby optimizing esthetic outcomes and tissue healing [41]. Recent advancements have introduced innovative techniques such as the single flap approach (SFA), connective tissue graft wall technique, non-incised papilla surgical approach, and modified vestibular incision subperiosteal tunnel access (M-VISTA).

The SFA, characterized by the elevation of a mucoperiosteal flap on one side while preserving soft tissues on the opposite side, exemplifies the pursuit of optimal esthetic outcomes [42]. Similarly, the connective tissue graft wall technique, coupled with enamel matrix derivative, presents a formidable approach for treating deep vertical bony defects and associated gingival recession [43].

In alignment with the ethos of minimally invasive surgery, the non-incised papilla surgical approach and M-VISTA prioritize tissue preservation and esthetic integrity by minimizing trauma to marginal tissues and avoiding unnecessary incisions [44, 45].

Moreover, the minimal access flap (MAF) technique and closed surgical technique (CST) exemplify the commitment to minimally invasive principles by retaining tissue integrity and promoting regeneration while minimizing patient discomfort [46].

In summary, the relentless pursuit of precision and patient-centric care underscores the ongoing evolution of minimally invasive surgical approaches in periodontics. By amalgamating cutting-edge techniques with a steadfast commitment to optimal outcomes, MIS stands as a beacon of innovation in modern periodontal therapy.

11. Advances in perio-ortho treatment

Patients grappling with periodontitis often necessitate an interdisciplinary approach that includes orthodontic intervention to effectively restore masticatory function, aesthetics, and overall quality of life. Progressive loss of periodontal tissues can lead to tooth drifting, flaring, secondary occlusal trauma, bite collapse, masticatory dysfunction, and ultimately tooth loss [47]. These considerations are integral to the newly introduced Classification of Periodontal and Peri-implant Diseases, where they serve as diagnostic criteria for stage IV, representing the most severe form of periodontitis. Guidelines published by the European Federation of Periodontology provide detailed insights into the timing of orthodontic treatment (OT) in periodontally compromised patients. It is recommended to commence OT only once the endpoints of periodontal therapy have been met, typically characterized by the absence of sites with probing pocket depth (PPD) ≤ 5 mm and positive bleeding on probing (BOP), along with the absence of sites with PPD ≥ 6 mm. These endpoints are usually achieved following non-surgical or surgical periodontal therapy as deemed necessary [48].

For teeth with intrabony defects, OT can be initiated soon after surgical treatment, as this combined approach has demonstrated favorable clinical outcomes and enhances the long-term prognosis of severely periodontally compromised teeth [49, 50]. Incisors afflicted with bone loss are particularly susceptible to elongation owing to the absence of occlusal and anteroposterior contacts. In cases of severe tooth loss inhibiting vertical migration during orthodontic correction, intrusion and retraction maneuvers are often necessary. Circumferential supracrestal fibrotomy, repeated monthly during intrusive movement, may reduce marginal bone resorption and facilitate these corrective movements.

Addressing gingival recession therapy, situations where the root is in close proximity to or beyond the cortical bone may benefit from orthodontic repositioning of the root within the bone prior to surgical root coverage procedures. Clear aligners, alongside traditional brackets, serve as effective tools for repositioning lower incisors’ roots before surgical root coverage procedures [51]. Moreover, periodontal phenotype modification therapy (PhMT), encompassing hard tissue augmentation (PhMT-b) or soft tissue augmentation (PhMT-s), prior to OT initiation could prevent loss of periodontal support and gingival recession, particularly in patients with thin and scalloped phenotypes [52].

Lastly, the latest advancements in combined periodontal and orthodontic treatment include the utilization of osseointegrated implants as orthodontic anchorage. These implants offer superior orthodontic anchorage compared to traditional tooth-borne devices, particularly beneficial in cases of inadequate periodontal anchorage, patient non-compliance with anchorage aids, aesthetic concerns or the desire to avoid post-growth completion orthognathic surgery [53].

These advancements underscore the evolving landscape of periodontal-orthodontic treatment, where integrated approaches hold immense potential for optimizing patient outcomes and overall treatment efficacy.

12. Biomaterials for periodontal regeneration

Periodontal therapy aims at achieving new periodontal attachment formation, making guided tissue regeneration (GTR) a pivotal surgical technique [54]. Barrier biomaterials play a crucial role by physically impeding fast-growing soft tissue cells like epithelial cells and gingival fibroblasts from infiltrating defective sites during periodontal regeneration. While the initial GTR membranes utilized non-resorbable materials, such as expanded polytetrafluoroethylene, the advent of resorbable membranes like collagen addressed the need for membrane removal surgeries. Recent decades have witnessed the development of membranes from synthetic polymers and naturally derived sources like collagen-based, chitosan, alginate, as well as occlusive titanium and micro-perforated titanium membranes. Additionally, advancements in tissue engineering and the integration of drug delivery systems into membranes hold promise for enhancing the barrier concept associated with guided bone regeneration (GBR) [55].

To achieve periodontal regeneration and alveolar ridge reconstruction, graft materials are commonly employed in conjunction with barrier membranes. These materials encompass autografts, allografts, xenografts, and alloplastic materials. While conventional biomaterials remain primary sources for periodontal regeneration, recent years have seen the development of new biomaterials for cementum, periodontal ligament (PDL), and alveolar bone regeneration. Ceramic biomaterials like calcium phosphate (CaP), calcium sulfate (CS), and bioactive glass (BG) exhibit characteristics conducive to hard tissue engineering due to their composition similar to bone mineral and their capacity to stimulate cell proliferation and differentiation [56]. With the emergence of tissue engineering and additive manufacturing, novel approaches like cell sheet engineering and multiphasic scaffolds have surfaced, with current research focusing on regenerating cementum, PDL, or the entire periodontium [57]. Furthermore, 3D printing facilitates the creation of precise scaffolds with controlled shape and porosity, with biomimetic 3D printing scaffolds being developed for regenerating complex alveolar bone-PDL-cementum structures [54].

A recent approach revolves around employing bioactive agents (BAs) to treat intra-osseous and furcation defects in conjunction with grafts and/or GTR. BAs such as recombinant human platelet-derived growth factor-BB (rhPDGF-BB), fibroblast growth factor (FGF), insulin-like growth factor (IGF), bone morphogenetic proteins (BMPs), platelet-rich plasma (PRP), enamel matrix derivative (EMD), and peptide P-15 (P-15) have been clinically evaluated for treating periodontal defects [42]. EMD and PRP products have garnered considerable interest and are widely utilized for periodontal regeneration. EMD, for instance, has demonstrated efficacy in intrabony defects, particularly when coupled with minimally invasive surgical techniques or flapless techniques, thereby enhancing initial wound stability and minimizing patient morbidity. Moreover, EMD has shown promise in recession defects, both alone and as an adjunct to soft tissue grafting, as well as in furcation defects [58]. Looking ahead, EMD’s applications are expanding to include supraalveolar-type defects with access flap surgery and possibly the treatment of peri-implantitis and mucosal recessions around implants [59].

Clinical research suggests that combined therapy involving platelet-rich plasma (PRP) with bone grafts and/or cells holds potential for ridge augmentation procedures. However, further randomized controlled trials (RCTs) are necessary to ascertain the superiority of specific autologous platelet concentrates (APCs). While APCs may expedite clinical healing, soft tissue epithelialization, and reduce postoperative pain in ridge preservation procedures, evidence regarding their significant impact on hard tissue regeneration remains inconclusive [55].

These advancements underscore a promising trajectory in the field of periodontal regeneration, with ongoing research poised to drive further innovation and clinical application.

13. Conclusions

In recent years, both medicine and dentistry have experienced significant advancements. Within dentistry, particularly in periodontology, there has been a rapid evolution in research and clinical approaches. This evolution spans various aspects, including prevention, diagnosis, prognosis, and treatment of periodontal diseases. Notably, there has been a shift toward prioritizing patient satisfaction by adopting less-invasive therapeutic approaches and emphasizing regeneration techniques aimed at restoring the original architecture of periodontal tissues.

Furthermore, innovations in antibiotic-probiotic treatment modalities have emerged, leveraging insights from the exploration of new bacteria and biofilm construction. This enhanced understanding has paved the way for more personalized periodontal treatment strategies tailored to individual genetic factors. Additionally, the introduction of robotic surgical techniques holds promise for minimizing trauma and enhancing surgical precision in periodontal interventions.

Overall, these advancements reflect a concerted effort within the field of periodontology to embrace cutting-edge technologies and evidence-based practices, ultimately aiming to improve patient outcomes and quality of care.