The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Clinical and laboratory assessment of the state of periapical tissues in systemic lupus erythematosus.

OBJECTIVE: Aim: To evaluate changes in clinical and laboratory parameters in patients with SLE depending on the severity and activity of the disease. PATIENTS AND METHODS: Materials and Methods: The study included 50 patients with SLE of different age groups, 10 men and 40 women. RESULTS: Results: Systemic lupus erythematosus (SLE) is a chronic disease that belongs to the group of rheumatic diseases and is characterised by autoimmune tissue damage. Chronic inflammatory periodontal diseases remain one of the most common dental pathologies. Chronic gingivitis and periodontitis in SLE are described as one of the earliest and most striking symptoms of the disease. Approximately the same trend was found in patients with SLE depending on the degree of clinical and laboratory activity of the disease. Patients with minimal, 1 degree of activity (characterized by the longest duration of SLE) showed the greatest decrease in bone mineral density (up to 2.25 points), and patients with higher activity had a significantly shorter duration of SLE and, accordingly, a smaller decrease in bone mineral density: in patients with 2 degrees of activity (1.79 points), with 3 degrees of activity (1.94 points). CONCLUSION: Conclusions: In patients with acute SLE, the maximum value of the Muhlemann-Cowell index was 2.31 points, in patients with subacute SLE - 1.89 points, and in patients with chronic SLE - 1.58 points. CPITN values increase inversely with the nature of the course of SLE, which is associated with the duration of the underlying disease.

Characterization of cells in blood evoked from periapical tissues in immature teeth with pulp necrosis and their potential for autologous cell therapy in Regenerative Endodontics.

OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.

Identification of root canal microbiota profiles of periapical tissue diseases using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

OBJECTIVES: The purpose of this study was to identify microorganisms isolated from various periapical tissue diseases using Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS) and classify them via an unsupervised machine learning approach. METHODS: A total of 150 patients with various apical conditions and teeth in need of endodontic retreatment were divided into five groups, including Retreatment, Acute Apical Abscess, Chronic Apical Abscess, Acute Apical Periodontitis, and Chronic Apical Periodontitis. Samples were collected from root canals using paper points after agitating with a #10 K file then microorganisms were identified using MALDI-TOF-MS. Data were analyzed using a hierarchical clustering method. Quadruple clusters and dendrograms were formed according to similarities and dissimilarities. RESULTS: A total of 80 species were identified representative of six different phyla. The most similar microorganism species identified were: ''Enterococcus faecalis'' between 21 and 23-year-old female cases in Retreatment group; ''Lactobacillus rhamnosus'' between 20 and 18-year-old male cases in Symptomatic Apical Abscess cases; ''Lactobacillus paracasei'' between 26 and 40-year-old male cases in Asymptomatic Apical Abscess cases; ''Enterococcus faecalis'' between 48 and 50-year-old female cases in Symptomatic Apical Periodontitis cases; ''Lactobacillus rhamnosus'' between 48 and 60-year-old male cases in Asymptomatic Apical Periodontitis cases. CONCLUSIONS: MALDI-TOF MS can be considered a fast and high-throughput screening technique for microbial species identification in endodontics. Thus, it will provide valuable data for future research designs regarding periapical tissue diseases. As the MALDI-TOF MS database expands and comprehensive data becomes available, the relationship between microbial profiles and disease progression will become increasingly apparent.

Nociceptors regulate osteoimmune transcriptomic response to infection.

Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is growing evidence that the nociceptive fibers densely innervating affected tissues regulate disease progression; therefore, we hypothesized that nociceptors regulate the transcriptomic profile of the periapical osteolytic lesion in a mouse model of apical periodontitis. Male control and nociceptor-ablated mice underwent pulp exposures, and after 0, 7, or 14 days, total RNA from periapical tissues was submitted for sequencing and bioinformatic analysis. Pulp exposure triggers the differential expression of hundreds of genes over the course of infection. At 14 days post pulp exposure, 422 genes, including Tnf, Il1a, and Il1b, were differentially expressed between nociceptor-ablated and control mice with greater enrichment of biological processes related to inflammation in nociceptor-ablated mice. Nociceptor ablation regulates the transcriptomic profile of periapical lesions in a mouse model of apical periodontitis, shifting the gene expression profile to a greater enrichment of inflammatory genes, suggesting nociceptors play a role in the kinetics of the immune response. This newly uncovered neuro-immune axis and its mechanisms in apical periodontitis can be an important therapeutic target for the treatment of this prevalent disease.

Efficacy of imaging techniques for the diagnosis of apical periodontitis: A systematic review.

BACKGROUND: Apical periodontitis (AP) is a chronic inflammatory response of microbial aetiology. Pathological changes associated with AP may not be visible on radiographic images and may linger without causing any symptoms. Clinicians rely mostly on clinical examination and imaging techniques to establish a diagnosis. OBJECTIVES: The aim of this review was to answer the following question using the PICO format: In the adult human permanent dentition (P), what is the efficacy of diagnostic imaging of the periapical tissues (I) using histopathology as a reference standard (C) in the diagnosis of apical periodontitis, in terms of diagnostic accuracy (O). METHODS: MEDLINE, EMBASE, Scopus and Cochrane Library were searched for English articles published through October 2021. At least two independent reviewers evaluated the study design, imaging modality used, histopathological assessment, outcome measures, results and conclusions for each article. The risk of bias was assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies-2. RESULTS: The initial search strategy identified 544 articles. Seven articles were included for analysis in the final review, all of which involved tissue samples obtained from cadavers. No clinical studies were identified that met the eligibility criteria. A consistently low sensitivity score and negative predictive value were reported for periapical radiography, especially in comparison to CBCT, which scored highly. Both modalities achieved high scores for specificity and positive predictive value. Diagnostic accuracy of CBCT was lower for root-filled teeth in comparison to non-root-filled teeth. DISCUSSION: Assessment of the periapical tissues using periapical radiographs was shown to have a low to moderate agreement with the histopathological assessment. CBCT was reported to be more accurate than PR and demonstrated a good agreement with histopathology, especially for non-root-filled teeth. CONCLUSIONS: This review identified a need for greater standardization in methodology and reporting, and as the findings are based on cadaver studies, their clinical relevance must be interpreted with caution. REGISTRATION: PROSPERO (CRD42021272147).

Impact of systemic health on treatment outcomes in endodontics.

BACKGROUND: The healing of periapical lesions after root canal treatment (RCT) is not the result of the curative action of the treatment. The process of healing begins with inflammation, and is resolved by the clearance of the immunogen that induces the immune response. Then, the periapical tissue itself carries out the healing of the periapical lesion, by repair or by a combination of repair and regeneration, depending on the host's reparative response working properly. The ultimate objective of RCT is to achieve wound healing by removing the source of bacterial antigens and toxins, allowing chronic inflammatory tissue to become reparative tissue. Some systemic conditions increase the susceptibility of the host to infection or impair the tissue reparative response, maintaining the inflammatory process and periapical bone resorption after RCT. This can cause the failure of RCT and even the need for extraction of the affected tooth. OBJECTIVE: To analyse the scientific literature on the possible influence of systemic conditions on the treatment outcomes in endodontics, as well as to discuss the biological mechanisms that may be involved. METHODS: The search was carried out in PubMed, SCOPUS and EMBASE. The inclusion criteria established were original scientific articles reporting data about some systemic condition in relation to treatment outcomes in endodontics, including clinical studies and studies carried out in animal models. RESULTS: Systemic factors (age, nutrition, stress, hormones, smoking habits), and systemic diseases, such as diabetes, cardiovascular diseases, osteoporosis, HIV infection, inflammatory bowel disease, and others, can influence or interfere in the repair of periapical tissues after RCT. DISCUSSION: Some of these systemic diseases can alter bone turnover and fibroblast function, preventing or delaying periapical wound healing. Others can alter the microvasculature, reducing nutrients and oxygen supply to periapical tissues. As a result, these systemic conditions can decrease the success rate of RCT and provoke incomplete wound healing (typically granulomatous tissue formation) in the periapical region. CONCLUSIONS: The results of this narrative review show worse success rate of RCT, with higher percentage of postoperative radiolucent periapical lesions and higher proportion of non-retained teeth (RFT), associated with several systemic conditions, such as smoking habits and diabetes.

The Potential Immunomodulatory Roles of Semaphorin 4D in Human Periapical Lesions.

INTRODUCTION: Semaphorin 4D (SEMA4D) is an important immunoregulator in the development of inflammatory diseases. Currently, the role of SEMA4D in human apical periodontitis remains unclear. This study aims to investigate the expression of SEMA4D and its potential immunomodulatory roles in apical periodontitis. METHODS: A total of 31 periapical tissues and 6 healthy gingival tissues were used in this experiment. Hematoxylin-eosin staining, immunohistochemical staining, and multiplex immunofluorescence staining were performed for histologic examination and immunochemical analysis. For data processing, the number of SEMA4D+, CD4+, CD8+, and CD20+ cells was analyzed by QuPath. In addition, the colocalization of SEMA4D with CD4, CD8, and CD20 was detected. RESULTS: Radicular cysts (RCs) (n = 18) and periapical granulomas (PGs) (n = 13) were identified by histologic evaluation. The number of SEMA4D+ cells in PGs was significantly greater than that in RCs (P < .05). T-cell and B-cell infiltration did not differ significantly between RCs and PGs. An increased number of CD20+ cells was observed in both types of apical periodontitis compared to CD8+ cells and CD4+ cells. Additionally, the presence of SEMA4D/CD4 and SEMA4D/CD20 double-positive cells was also markedly higher in PGs than in RCs. CONCLUSION: The expression of SEMA4D and related immune cells showed different characteristics between RCs and PGs. The disparate expression patterns indicated the possible different pathologic states of the 2 types of periapical lesions. This study provides a new perspective on the description of the comprehensive microenvironment of periapical lesions.

Accurate detection for dental implant and peri-implant tissue by transfer learning of faster R-CNN: a diagnostic accuracy study.

BACKGROUND: The diagnosis of dental implants and the periapical tissues using periapical radiographs is crucial. Recently, artificial intelligence has shown a rapid advancement in the field of radiographic imaging. PURPOSE: This study attempted to detect dental implants and peri-implant tissues by using a deep learning method known as object detection on the implant image of periapical radiographs. METHODS: After implant treatment, the periapical images were collected and data were processed by labeling the dental implant and peri-implant tissue together in the images. Next, 300 images of the periapical radiographs were split into 80:20 ratio (i.e. 80% of the data were used for training the model while 20% were used for testing the model). These were evaluated using an object detection model known as Faster R-CNN, which simultaneously performs classification and localization. This model was evaluated on the classification performance using metrics, including precision, recall, and F1 score. Additionally, in order to assess the localization performance, an evaluation through intersection over union (IoU) was utilized, and, Average Precision (AP) was used to assess both the classification and localization performance. RESULTS: Considering the classification performance, precision = 0.977, recall = 0.992, and F1 score = 0.984 were derived. The indicator of localization was derived as mean IoU = 0.907. On the other hand, considering the indicators of both classification and localization performance, AP showed an object detection level of AP@0.5 = 0.996 and AP@0.75 = 0.967. CONCLUSION: Thus, the implementation of Faster R-CNN model for object detection on 300 periapical radiographic images including dental implants, resulted in high-quality object detection for dental implants and peri-implant tissues.

Tissue Characteristics in Endodontic Regeneration: A Systematic Review.

The regenerative endodontic procedure (REP) represents a treatment option for immature necrotic teeth with a periapical lesion. Currently, this therapy has a wide field of pre-clinical and clinical applications, but no standardization exists regarding successful criteria. Thus, by analysis of animal and human studies, the aim of this systematic review was to highlight the main characteristics of the tissue generated by REP. A customized search of PubMed, EMBASE, Scopus, and Web of Science databases from January 2000 to January 2022 was conducted. Seventy-five human and forty-nine animal studies were selected. In humans, the evaluation criteria were clinical 2D and 3D radiographic examinations. Most of the studies identified a successful REP with an asymptomatic tooth, apical lesion healing, and increased root thickness and length. In animals, histological and radiological criteria were considered. Newly formed tissues in the canals were fibrous, cementum, or bone-like tissues along the dentine walls depending on the area of the root. REP assured tooth development and viability. However, further studies are needed to identify procedures to successfully reproduce the physiological structure and function of the dentin-pulp complex.

Unusual Lesion Caused by Food Displacement Into the Oral Mucosa, Mimicking a Sinus Tract.

This article reports an unusual case of foreign body lesion on the oral mucosa. A 61-year-old man, with no previous traumatic episode, presented with a small swelling resembling a sinus tract on the mucosa in the anterior mandible, adjacent to the left central and lateral incisors. Because of a discrete drainage of serous/purulent exudate, the clinician initially suspected endodontic involvement; however, the adjacent teeth were caries-free, responded positively to pulp tests, and the periapical tissues were radiographically normal. Exploration of the lesion opening under an operating microscope revealed a small seed associated with a dark filamentous structure; both were removed and processed for histologic examination. The seed was from a fig, and was germinating under the mucosa conditions. Bacterial colonization of the vegetable structures and polymorphonuclear leukocyte accumulations were histologically observed. The mucosa healed completely and uneventfully over the following weeks.

Present status and future directions of intracanal medicaments.

Two fundamental goals of endodontic treatment are to prevent or treat apical periodontitis. From a predictive perspective, several variables can affect the outcome of root canal treatment. Some of these variables depend on intraoperative factors, which include irrigation technique, size of the apical preparation, use of intracanal medicaments or the number of appointments necessary to complete the treatment. However, the outcome may also be affected by host and microbial factors. The intensity of periradicular bone loss or tissue damage, the presence of preoperative pain and associated conditions such as mechanical allodynia and central sensitization, the anatomical complexity of the apical portion of the canal, and the virulence and longevity of the bacterial infection can all have a profound influence on the outcome. Furthermore, numerous medical conditions have been reported to decrease the capability of the immune system to heal the periapical tissues. It is the clinician's responsibility to analyse these variables and incorporate them into the disinfection strategy to maximize the chances of healing. This narrative review will focus on the present status of intracanal medicaments, the clinical indications for their use and future directions for research.

Pulpal and periapical tissue response after direct pulp capping with endosequence root repair material and low-level laser application.

BACKGROUND: The study aims to investigate the pulp and periapical reaction and healing after capping with EndoSequence Root Repair Material (ERRM) combined with low-level laser application. METHODS: In 6 rabbits, pulps were exposed via class V, half of the samples received a low-level diode laser at 980 nm. Thereafter, cavities were capped with regular-set ERRM. The specimens were processed for histomorphological examination after 2 weeks and two months. RESULTS: After 2 weeks, images show mild inflammation and organized odontoblasts in lased group. The non-lased group shows more severe inflammation. The predentin thickness was thicker in the lased group with statistical significance (p < 0.05). After 2 months, inflammatory cells were sparse in both lased and non-lased groups. In the periapical area, group one showed dilated blood vessels and thick fibrous connective tissues. In group two, there were more numerous maturations of PDL fibers with scattered inflammatory cells and congested blood vessel. CONCLUSIONS: Using low-level laser therapy in combination with ERRM for pulp capping shortens the inflammatory phase and enhances healing.

Does simultaneous soft tissue augmentation around immediate or delayed dental implant placement using sub-epithelial connective tissue graft provide better outcomes compared to other treatment options? A systematic review and meta-analysis.

OBJECTIVE: The clinical benefits of simultaneous implant placement and soft tissue augmentation using different treatment modalities are unclear. The current meta-analysis aimed to compare the effect of simultaneous soft tissue augmentation using subepithelial connective tissue graft (SCTG) around immediate or delayed dental implant placement with other treatment modalities on the peri-implant tissue health and esthetic. METHODS: Up to May 2021, four databases (PubMed, EMBASE, Cochrane Central, and Google Scholar) were searched. Randomized control trials with follow-up >3 months, evaluating simultaneous implant placement (immediate or delayed) and soft tissue augmentation using SCTG compared with other treatment modalities were included. The predictor variables were SCTG versus no augmentation with/without guided bone regeneration (GBR) or other augmentation techniques (Acellular dermal matrix (ADM), Xenogeneic collagen matrix (XCM). The outcome variables were buccal tissue thickness (BTT), mid-buccal gingival level (MGL), marginal bone loss (MBL), and pink esthetic scores (PES). Cumulative mean differences (MD) and 95% confidence interval (CI) were estimated. RESULTS: Twelve studies were included. SCTG along with immediate implant placement (IIP) or delayed implant placement (DIP) showed a statistically significant improvement in BTT (Fixed; MD, 0.74; 95% CI, 0.51; 0.97), MGL (Fixed; MD, 0.5; 95% CI, 0.21; 0.80), PES (Fixed; MD, 0.79; 95% CI, 0.29; 1.29), and less MBL (Fixed; MD, -0.11; 95% CI, -0.14; -0.08) compared to no graft (P<0.05). A statistically insignificant differences in BTT (Random; MD, 0.62; 95% CI, -0.41; 1.65), MGL (Fixed; MD, -0.06; 95% CI, -0.23; 0.11), MBL (Fixed; MD, 0.36; 95% CI, -0.05; 0.77) and PES (Fixed; MD, 0.28; 95% CI, -0.10; 0.67) was observed when SCTG along with DIP was compared with no augmentation plus GBR. Similarly, no statistically significant difference was observed when comparing SCTG along with DIP with acellular dermal matrix (ADM) concerning BTT (MD:0.71, P = 0.18) and KMW (MD: 0.6, P = 0.19). CONCLUSION: There is a very low quality of evidence to provide recommendations on whether simultaneous dental implant placement (IIP or DIP) and soft tissue augmentation using SCTG is superior to no augmentation or is comparable to the other tissue augmentation materials in improving the quality and quantity of peri-implant tissues. Therefore, further, well-designed RCTs with larger sample sizes and long follow-up times are still needed.

Regenerative Endodontic Treatment Using Periapical Blood or Circulating Blood as Scaffold: A Volumetric Analysis.

INTRODUCTION: Circulating blood is a readily available scaffold when enough bleeding cannot be induced from periapical tissues during regenerative endodontic treatments (RETs). The aim of this investigation was to compare the radiographic outcome (ie, linear and 3-dimensional volumetric) of RET using periapical blood or circulating blood as scaffolds in sheep immature mandibular incisors. METHODS: Thirty-two immature sheep mandibular central incisors were randomly assigned to the following groups (n = 8): the positive control groups, the pulps were removed without any treatment; the periapical blood group, RET was performed using periapical blood as the scaffold; the circulating blood group, RET was performed using circulating blood as the scaffold; and the negative control group, intact teeth without any treatment. After 8 months, micro-computed tomographic images of mandibular blocks were taken to assess the following: root length, root thickness at the midroot and cementoenamel junction levels, and the incidence of apical closure. Root structures were segmented, and root volumes were calculated and analyzed statistically. RESULTS: RET using periapical blood and circulating blood resulted in increases in root length and root wall thickness at the midroot and cementoenamel junction levels, the incidence of apical closure, and root volume (P < .05). There were no significant differences between the RET groups and the negative control group regarding linear measurements (ie, root length, root thickness, and apical closure) (P > .05). The root volumes of the 2 RET groups were similar (P > .05) and were less than those observed in the negative control group (P < .05). CONCLUSIONS: There were no significant radiographic differences between the RET groups using periapical blood and circulating blood as scaffolds. RET resulted in less root volume compared with normal root development.

A critical analysis of research methods and experimental models to study apical extrusion of debris and irrigants.

During root canal treatment, intra-canal content as well as irrigants and root filling materials may be extruded into the periapical tissues, leading to undesirable consequences such as delay of healing and flare-ups. Although apical extrusion of debris is an inherent occurrence of root canal treatment and no instrument or technique has totally solved this problem, attempts are underway to minimize the harm exerted to periapical tissues with the development of new techniques. This has led researchers to continuously evaluate new instruments and methodologies in terms of apical extrusion. New research on extrusion is frequently published some of which utilize traditional experimental designs and others assessing extrusion using modified or innovative methodologies. This review focuses on the research methods and experimental models to study apical extrusion of debris and irrigants by making a critical analysis of each technique. A PubMed and Scopus search was conducted and 144 articles relevant to apical extrusion were retrieved from 1968 until 2021. The methodologies used in every research article were evaluated and a classification was created. Each methodology is described with the general outlines and advantages and drawbacks of each technique summarized with a critical approach. It appears that the collection of debris in a vial still serves as a method chosen by authors even in most recent studies. On the other hand, development of experimental models that include multiple factors considering the drawbacks of the existing study designs is essential to draw more reliable conclusions on the apical extrusion phenomenon.

Local Immunomodulatory Effects of Intracanal Medications in Apical Periodontitis.

The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP), and periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly because of the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered posttreatment healing to exacerbation of chronic periradicular immune response, which compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment; however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. The interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of nonconventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect without any host tissue damages. In this review, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobial intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics.

REPARATIVE REGENERATION OF PERIAPICAL TISSUES IN CHRONIC GRANULOMATOUS PERIODONTITIS UNDER THE INFLUENCE OF COMPOSITION BASED ON CALCIUM HYDROXYAPATITE.

OBJECTIVE: The aim: To establish the dynamics of reparation processes in periapical tissues in chronic granulomatous periodontitis under the influence of the developed composition based on calcium hydroxyapatite in comparison with the generally accepted drug MTA. PATIENTS AND METHODS: Materials and methods: The main group included 52 individuals, and the comparison group - 19 patients with chronic granulomatous periodontitis. In the first experimental subgroup, patients were obturated of the tooth root apical area with the proposed composition, and in the second experimental subgroup patients were performed obturation of the root canal apical area with additional transcanal withdrawal of the composition into the periapical area. In the comparison group, the tooth root apex was obturated with MTA material. RESULTS: Results: Clinical studies have shown that the composition based on calcium hydroxyapatite, having osteoconductive, antioxidant and anti-inflammatory properties, activates the synthesis of organic and mineral components, that promotes the bioreparation and regeneration processes of periapical tissues in chronic granulomatous periodontitis, which occurred most intensively during the first 6 months after treatment. At the same time, with additional transcanal removal of the filling composition based on calcium hydroxyapatite into the periapical area in patients with chronic granulomatous periodontitis with acquired wide tooth root apex was observed in 1.6 time better results than the method of creating an apical root canal obturation (p <0,05), indicating a high therapeutic effect. CONCLUSION: Conclusions: Composition based on calcium hydroxyapatite, having osteoconductive, antioxidant and anti-inflammatory properties, activates the synthesis of organic and mineral components, which promotes the processes of bioreparation and regeneration of periapical tissues, especially in the early stages. And additional transcanal removal of the filling composition into the periapical space causes the acceleration of the period of periodontal tissues revitalization, bioreparation and regeneration compared to the creation of the apical obturation within the physiological tooth root apex.

An Epigallocatechin-3-gallate Formulation Developed for Endodontic Use: A Physicochemical and Biological Evaluation.

INTRODUCTION: Although epigallocatechin-3-gallate (EGCG) from green tea has been successfully used in the prevention and treatment of several infectious and immunoinflammatory diseases because of its proven anti-inflammatory, antioxidant, antimicrobial, and antiresorptive role, its use as an intracanal dressing has not been proposed. The aim of this study was to develop a formulation based on EGCG for endodontic use by assessing its physicochemical and biological properties. METHODS: Initially, physicochemical characterization of EGCG was performed by ultraviolet-visible and fluorescence spectroscopy to evaluate if the properties were maintained in acidic pH and time (1-6, 24, and 27 hours). After that, biological studies evaluated the developed formulation of EGCG at different concentrations (1.25, 5, 10, and 20 mg/mL). The tissue compatibility with subcutaneous tissue of mice was evaluated by plasma leakage after 24 hours and the examination of macroscopic and microscopic features at 7, 21, and 63 days after the insertion of polyethylene tubes containing the formulations. The repair of experimentally induced periapical lesions in dog's teeth by radiographic and histopathologic analysis was also evaluated. The scores were statistically analyzed by the chi-square and Fisher exact test. Analysis of variance followed by the Tukey posttest were used for the quantitative analysis. The significance level was 5%. RESULTS: The physicochemical characterization performed under ultraviolet-visible spectrophotometry showed that the EGCG properties remained unaltered in acid pH and function of time, keeping its wavelength to 274 nm. Macroscopic parameters evaluated at 7, 21, and 63 days showed that all concentrations presented no epithelial ulceration or presence of mild superficial tissue necrosis, edema, or vascularization with no significant difference in the control group. During all periods of microscopic examination, all groups presented the absence of abscess foci and edema and the presence of fibrous capsule and neovascularization. The presence of reparative tissue with a gentle presence of neutrophilic inflammatory cells was also observed for all groups, except for the calcium hydroxide paste group, which presented a more pronounced inflammation and tissue necrosis at days 7 and 21 (P < .001). At day 63, all groups presented an absence of inflammatory infiltrate and necrosis. The evaluation of dog teeth showed that treatment with the EGCG formulation provided a reduction of the periapical radiolucent area and allowed the repair of apical and periapical tissues (P > .05). CONCLUSIONS: The developed formulation based on EGCG from green tea presented physicochemical stability and tissue compatibility and provided the repair of periapical lesions when used as an intracanal dressing.

Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues.

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.