Retrospective Evaluation of Periradicular Biopsies: An 18-Year Study.

INTRODUCTION: Radiographic findings in periradicular areas are repeatedly associated with infected root canal systems. Although non-odontogenic lesions in teeth are reported to be low, they often mimic periapical pathoses, and consequently, histopathologic examinations after surgical revisions are nurtured. METHODS: Biopsies submitted to the College of Dentistry between 2003 and 2021 were reviewed. Clinicopathologic characteristics were collected, including age, sex, medical history, location, sensibility tests, and clinic impressions from each specimen. Histopathologic diagnosis and gross description were also part of our database. RESULTS: A total of 72,055 pathology reports were reviewed, of which 10,031 lesions (13.9%) met the criterion of being intraosseous lesions at the periradicular area. Among those 10,031 lesions, 7.94% (n = 796) were of non-endodontic origin, 7153 were documented as non-vital, and 2.36% (n = 169) of these non-vital teeth were diagnosed with a non-endodontic origin. A total of 5707 lesions were obtained from surgeries within the periapical tissues, primarily performed by endodontists (94.02%). Non-endodontic lesions were reported in 1.09% of the cases. Odontogenic keratocyst was the most common non-endodontic diagnosis, followed by nasopalatine duct cyst and benign fibro-osseous lesion, respectively. CONCLUSIONS: Pathologic findings of the periradicular tissues are not always from endodontic origin. The probability of encountering non-endodontic lesions is almost 8%. Even in clinically reported teeth with pulp necrosis, 1%-3% of biopsies were confirmed as non-endodontic lesions.

Exploring microRNAs in craniofacial regenerative medicine.

microRNAs (miRs) have been reported over the decades as important regulators in bone development and bone regeneration. They play important roles in maintaining the stem cell signature as well as regulating stem cell fate decisions. Thus, delivering miRs and miR inhibitors to the defect site is a potential treatment towards craniofacial bone defects. However, there are challenges in translation of basic research to clinics, including the efficiency, specificity, and efficacy of miR manipulation methods and the safety of miR delivery systems. In this review, we will compare miR oligonucleotides, mimics and antagomirs as therapeutic reagents to treat disease and regenerate tissues. Newer technology will be discussed as well as the efficiency and efficacy of using these technologies to express or inhibit miRs in treating and repairing oral tissues. Delivery of these molecules using extracellular vesicles and nanoparticles can achieve different results and depending on their composition will elicit specific effects. We will highlight the specificity, toxicity, stability, and effectiveness of several miR systems in regenerative medicine.

Exploring craniofacial and dental development with microRNAs.

microRNAs (miRs) are small RNA molecules that regulate many cellular and developmental processes. They control gene expression pathways during specific developmental time points and are required for tissue homeostasis and stem cell maintenance. miRs as therapeutic reagents in tissue regeneration and repair hold great promise and new technologies are currently being designed to facilitate their expression or inhibition. Due to the large amount of miR research in cells and cancer many cellular processes and gene networks have been delineated however, their in vivo response can be different in complex tissues and organs. Specifically, this report will discuss animal developmental models to understand the role of miRs as well as xenograft, disease, and injury models. We will discuss the role of miRs in clinical studies including their diagnostic function, as well as their potential ability to correct craniofacial diseases.

Plasmid encoding miRNA-200c delivered by CaCO3-based nanoparticles enhances rat alveolar bone formation.

Aim: miRNAs have been shown to improve the restoration of craniofacial bone defects. This work aimed to enhance transfection efficiency and miR-200c-induced bone formation in alveolar bone defects via plasmid DNA encoding miR-200c delivery from CaCO3 nanoparticles. Materials & methods: The CaCO3/miR-200c delivery system was evaluated in vitro (microscopy, transfection efficiency, biocompatibility) and miR-200c-induced in vivo alveolar bone formation was assessed via micro-computed tomography and histology. Results: CaCO3 nanoparticles significantly enhanced the transfection of plasmid DNA encoding miR-200c without inflammatory effects and sustained miR-200c expression. CaCO3/miR-200c treatment in vivo significantly increased bone formation in rat alveolar bone defects. Conclusion: CaCO3 nanoparticles enhance miR-200c delivery to accelerate alveolar bone formation, thereby demonstrating the application of CaCO3/miR-200c to craniofacial bone defects.

The restoration of craniofacial bone defects is surgically complex and requires the combined use of bone grafts and regenerative biomaterials. miRNAs are small biomolecules that have been shown to improve bone regeneration in large bone defects. The aim of this work was to develop a nanoparticle-based delivery system to sustain the release of miRNAs to improve the restoration of craniofacial bone defects. The results of this study demonstrated that CaCO₃ nanoparticles extend the delivery of miRNAs to enhance bone formation in a craniofacial bone defect animal model in a therapeutically safe manner that improves upon conventional nanoparticle materials for bone regeneration. The findings attest to the regenerative properties of miRNAs and further indicate the potential application of CaCO₃-based nanoparticles in restoring large bone defects.

microRNA-126 inhibits vascular cell adhesion molecule-1 and interleukin-1beta in human dental pulp cells.

BACKGROUND: Vascular cell adhesion molecule (VCAM-1) mediates pulpitis via regulating interleukin (IL)-1ß. microRNA (miR)-126 was reported to regulate the VCAM-1 under many different pathophysiological circumstances. We investigated variations of miR-126 and VCAM-1 in inflamed patient pulp tissues and determined potential roles of miR-126 in pulpitis using human dental pulp cells (hDPCs) in vitro. METHODS: We quantitatively measured the transcripts of miR-126 and VCAM-1 in inflamed human pulp tissues using qRT-PCR and compared with those from healthy human pulp tissues. In addition, we transfected miR-126 in hDPCs using plasmid DNA (pDNA)-encoding miR-126 delivered by polyethylenimine (PEI) nanoparticles. RESULTS: The irreversible pulpitis significantly reduced miR-126 and increased the transcript of VCAM-1 in pulp tissues (p < 0.05). pDNA-encoding miR-126 delivered PEI nanoparticles and effectively upregulated the expression of miR-126 in hDPCs (p < 0.05). The overexpression of miR-126 could effectively suppress the transcripts and protein levels of VCAM-1 and IL-1ß induced by Pg-LPS at 100ng/mL in DPCs (p < 0.05). CONCLUSIONS: miR-126 is involved in pulpitis and downregulated the VCAM-1 and IL-1ß in DPCs. miR-126 may be a potential target to attenuate the inflammation of pulpitis.

Rat Calvarial Bone Regeneration by 3D-Printed ß-Tricalcium Phosphate Incorporating MicroRNA-200c.

Advanced fabrication methods for bone grafts designed to match defect sites that combine biodegradable, osteoconductive materials with potent, osteoinductive biologics would significantly impact the clinical treatment of large bone defects. In this study, we engineered synthetic bone grafts using a hybrid approach that combined three-dimensional (3D-)printed biodegradable, osteoconductive ß-tricalcium phosphate (ß-TCP) with osteoinductive microRNA(miR)-200c. 3D-printed ß-TCP scaffolds were fabricated utilizing a suspension-enclosing projection-stereolithography (SEPS) process to produce constructs with reproducible microarchitectures that enhanced the osteoconductive properties of ß-TCP. Collagen coating on 3D-printed ß-TCP scaffolds slowed the release of plasmid DNA encoding miR-200c compared to noncoated constructs. 3D-printed ß-TCP scaffolds coated with miR-200c-incorporated collagen increased the transfection efficiency of miR-200c of both rat and human BMSCs and additionally increased osteogenic differentiation of hBMSCs in vitro. Furthermore, miR-200c-incorporated scaffolds significantly enhanced bone regeneration in critical-sized rat calvarial defects. These results strongly indicate that bone grafts combining SEPS 3D-printed osteoconductive biomaterial-based scaffolds with osteoinductive miR-200c can be used as superior bone substitutes for the clinical treatment of large bone defects.

Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice.

The present study was conducted to characterize microRNA-200c (miR-200c) and its regulators in adipogenic differentiation, obesity, and periodontitis in obese subjects (PiOSs), and to determine the therapeutic efficacy of plasmid DNA encoding miR-200c as a treatment for PiOSs. We report that highly expressed miR-200c in gingival tissues was downregulated in diet-induced obese (DIO) mice and during adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). Local injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in the maxilla interdental gingiva of DIO mice reduced miR-200c in gingival and adipose tissues and induced periodontal inflammation associated with systemic elevation of interleukin-6 (IL-6) and impaired glucose tolerance. The inhibitory functions of Pg-LPS and IL-6 on miR-200c and their effectiveness on Zeb1 were confirmed in vitro. Injection of naked plasmid DNA encoding miR-200c into the gingiva effectively rescued miR-200c downregulation, prevented periodontal and systemic inflammation, and alleviated the impaired glucose metabolism in obese mice with LPS-induced periodontitis. Increased circulating exosomal miR-200c and its function on suppressing proinflammatory cytokines and adipogenesis explained the mechanism(s) of gingival application of miR-200c in attenuating systemic inflammation in PiOSs. These results demonstrated that miR-200c reduced by Pg-LPS and IL-6 in periodontitis and obesity might lead to the pathogenesis of PiOSs, and upregulation of miR-200c in the gingiva presents a therapeutic approach for PiOSs.

Optimal antimicrobial concentration of mixed antibiotic pastes in eliminating Enterococcus faecalis from root dentin.

This study aims to identify the optimal concentrations of triple antibiotic paste (TAP), modified triple antibiotic paste (mTAP) and double antibiotic paste (DAP) that could completely eradicate Enterococcus faecalis in dentinal tubules. One hundred and ninety extracted human premolars inoculated with E. faecalis were medicated with calcium hydroxide and mixed antibiotic pastes (TAP, mTAP and DAP at 0.1, 1.25, 5, 10 and 20 mg mL-1 of each drug) for seven days before being frozen, pulverised and cultured. Specimens treated with the lowest concentration of the mixed antibiotics capable of eradicating E. faecalis were examined using scanning electron and confocal laser scanning microscopy to confirm the eradication of the microbial. TAP at 10 mg mL-1 of each drug was able to completely eliminate bacteria inside dentinal tubules, whereas mTAP and DAP required 20 mg mL-1 of each drug. Calcium hydroxide was not effective in eradicating E. faecalis inside dentinal tubules.

Endodontic Management of a Chronic Periapical Abscess in a Maxillary Central Incisor with an Immature Root Apex Using Platelet-Rich Fibrin: A Case Report.

Platelet-rich fibrin (PRF) has been used for several treatments in dentistry. The present study reports the clinical and radiographic outcomes of a root canal treatment of a necrotic immature maxillary central incisor using PRF. A 15-year-old female patient presented with a diagnosis of maxillary left central incisor pulp necrosis with open apex and periapical radiolucency and extraoral sinus tract. Two months after a two-visit root canal treatment using calcium hydroxide as a root canal dressing, no clinical symptoms were observed, and the previous sinus tract at the patient's nostril had completely disappeared. In the subsequent visit, the PRF was prepared and delivered into the root canal. The PRF layer was covered with collagen membrane and then sealed with white mineral trioxide aggregate. One year later, the patient remained asymptomatic. Radiological examination using cone beam computed tomography (CBCT) showed that the destructive buccal alveolar bone was completely repaired.