Search Results (220)

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Bariatric surgery involves major changes in the anatomy and physiology of the gastrointestinal tract, which may alter oral drug bioavailability and efficacy. Phosphodiesterase-5 inhibitor (PDE5i) drugs are the first-line treatment of erectile dysfunction, a condition associated with a higher BMI. In this paper, we examine the PDE5i vardenafil for possible post-bariatric changes in solubility/dissolution and absorption. Vardenafil solubility was determined in vitro, as well as ex vivo using aspirated gastric contents from patients prior to vs. following bariatric procedures. Dissolution was tested in vitro under unoperated stomach vs. post-gastric sleeve/bypass conditions. Lastly, the gathered solubility/dissolution data were used to produce an in silico physiologically based pharmacokinetic (PBPK) model (GastroPlus^®), where gastric volume, pH, and transit time, as well as proximal GI bypass (when relevant) were all adjusted for, evaluating vardenafil dissolution, gastrointestinal compartmental absorption, and pharmacokinetics before vs. after different bariatric procedures. pH-dependent solubility was demonstrated for vardenafil with low (pH 7) vs. high solubility (pH 1–5), which was confirmed ex vivo. The impaired dissolution of all vardenafil doses under post-gastric bypass conditions was demonstrated, contrary to complete (100%) dissolution under pre-surgery and post-sleeve gastrectomy conditions. Compared to unoperated individuals, PBPK simulations revealed altered pharmacokinetics post-gastric bypass (but not after sleeve gastrectomy), with 30% lower peak plasma concentration (C_max) and 40% longer time to C_max (T_max). Complete absorption after gastric bypass is predicted for vardenafil, which is attributable to significant absorption from the large intestine. The biopharmaceutics and PBPK analysis indicate that vardenafil may be similarly effective after sleeve gastrectomy as before the procedure. However, results after gastric bypass question the effectiveness of this PDE5i. Specifically, vardenafil’s onset of action might be delayed and unpredictable, negatively affecting the practicality of the intended use. Full article

Odontogenic abscesses are a frequent and challenging clinical issue in pet rabbits, often requiring a comprehensive diagnostic and therapeutic approach. This review collates current evidence on the etiology, diagnosis, and treatment of rabbit odontogenic abscesses, with a focus on imaging advances, microbial diversity, and local antimicrobial therapies. Predisposing factors include congenital conformation, inappropriate diet (insufficient abrasiveness, calcium or Vit D deficiencies, etc.), trauma, and neoplasia. Imaging techniques such as CT and cone-beam CT (CBCT) enable early detection and surgical planning, while traditional radiography remains useful in general practice. Treatment includes systemic antibiotics, surgical curettage, and the use of localized delivery systems such as antibiotic-impregnated polymethyl methacrylate (AIPMMA) beads. Adjunctive therapies like Manuka honey are also discussed. Two original heatmaps summarize bacterial prevalence and antimicrobial resistance from six peer-reviewed studies. These visualizations highlight the polymicrobial nature of these infections and the emergence of multidrug-resistant strains. Preventive strategies focus on optimal diet, regular dental checks, and owner education. The review also identifies key gaps in the literature, including the underreporting of anaerobes and lack of standardized treatment protocols. This article aims to support veterinary professionals in delivering evidence-based, individualized care to improve outcomes in rabbits with odontogenic abscesses. Full article

Background/Objectives: Hypohidrotic ectodermal dysplasia (HED) is a rare hereditary disorder affecting ectoderm-derived tissues including teeth, hair, and sweat glands. The dental abnormalities associated with HED, such as oligodontia and conical teeth, often result in significant functional, esthetic, and psychosocial challenges, particularly during childhood. Methods: A 10-year-old child presented with psychosocial concerns related to missing and malformed teeth. Clinical examination revealed oligodontia, conical anterior teeth, and a resorbed mandibular ridge. Based on clinical findings and a positive family history, a diagnosis of HED with significant dental involvement was confirmed. Results: A conservative prosthodontic approach was selected. A maxillary overdenture was fabricated over the retained primary teeth to enhance retention and preserve the alveolar bone, and a resin-bonded bridge was placed in the mandible due to poor ridge anatomy. The treatment restored oral function and esthetics and improved the child’s self-esteem. A recall visit after three months confirmed good prosthesis adaptation and a positive response from the patient and parents. Conclusions: This case highlights the importance of early, conservative, and developmentally appropriate prosthetic rehabilitation in pediatric patients with HED. Interim prostheses can significantly improve oral function, appearance, and psychosocial well-being while preserving future treatment options as the child matures. Full article

The accurate identification and protection of the lingual nerve during oral surgery are critical to avoid complications such as a loss of taste or sensation and chronic pain. While numerous studies have described the nerve’s anatomy and injury outcomes, no consensus exists on the optimal method to trace its full course. This narrative review systematically examined the literature from 2010 to 2024, using databases like PubMed, MEDLINE, Embase, and Google Scholar. Keywords included “Lingual nerve,” “Course,” “Anatomy,” and “Clinical implications,” combined with Boolean operators. Studies were selected based on defined criteria, and findings were synthesized to highlight key challenges in diagnosing the nerve’s path. This review identifies difficulties at multiple anatomical sites: the foramen ovale, infratemporal fossa, pterygomandibular space, third molar and retromolar regions, premolar/molar areas, floor of the mouth, and anterior gingiva and tongue. Lingual nerve injury, especially during lower third molar surgeries, remains a major concern, often exacerbated by factors like patient age, unerupted teeth, and lingual surgical approaches. Effective prevention hinges on precise anatomical knowledge and meticulous surgical technique. Microsurgical repair remains the primary treatment but often yields unpredictable outcomes. Emerging regenerative therapies show early promise but require further clinical validation. Imaging tools such as magnetic resonance imaging (MRI) and ultrasound may enhance diagnostic accuracy and surgical planning; however, each has limitations in everyday practice. Ultimately, early identification, careful surgical handling, and appropriate imaging support are vital for improving patient outcomes and minimizing the risks of lingual nerve injury. Full article

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently assessed using an MTS assay. The anti-inflammatory activity of C. okamurae on Porphyromonas gingivalis (P. gingivalis)-stimulated RAW 264.7 macrophages was evaluated by measuring nitric oxide (NO) production. mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were quantified via quantitative real-time PCR (qRT-PCR). The protein expression of iNOS, p-IKKα/β, p-IκBα, and NF-κB p65 was examined using Western blot and immunofluorescence. The results demonstrated that C. okamurae extracts exhibited no cytotoxicity in RAW 264.7 macrophages at concentrations of 0.2, 2, 20, and 200 μg/mL. The extracts dose-dependently reduced NO production, downregulated mRNA levels of proinflammatory cytokines, and inhibited iNOS expression in P. gingivalis-stimulated RAW 264.7 macrophages, a model commonly used to study periodontal inflammation. Furthermore, the extracts suppressed the phosphorylation of IKKα/β and IκBα and prevented the NF-κB p65 nuclear translocation. These findings suggest that C. okamurae extracts inhibit NF-κB signaling activation triggered by the periodontal pathogen, highlighting their potential anti-inflammatory effects, relevant to periodontal disease. Full article

Phagocytes carry out their functions by organizing new subcellular structures. During phagocytosis, macrophages internalize and degrade pathogens and apoptotic cells by forming the phagocytic cup and phagosome. Osteoclasts resorb bone by forming the sealing zone and ruffled border at the ventral membrane. This review explores the organizational principles of these dynamic structures. In in vitro frustrated phagocytosis, specifically 2D phagocytosis by macrophages, the activation of the Fcγ receptor generates multiple self-organized waves containing F-actin, Arp2/3, and phosphoinositides. The propagation of these circular actin waves segregates the inside from the outside, leading to the compartmentalization of the ventral membrane. As the actin wave passes, cortical actin is disrupted, and membrane remodeling occurs within the wave, creating a new membrane domain with high exocytic activity. These processes mirror the formation of the constriction zone in the phagocytic cup and phagosome during 3D phagocytosis. A similar mechanism may also contribute to the formation of the sealing zone and ruffled border in osteoclasts. Based on these observations, we propose that dynamic structures formed from actin waves are organized through the fractal integration of self-organized, oscillatory substructures, with F-actin treadmilling fueling their formation and maintenance. Full article

Histology remains a cornerstone in medical and dental education, providing essential insights into tissue structure, function, and pathology. However, despite its foundational importance, interest in histology is declining, often due to outdated pedagogical methods, insufficient clinical context, and limited use of diverse teaching strategies. Modern health professionals require not only microscopic knowledge but also an understanding of the genetic mechanisms driving tissue development and disease. This paper critically evaluates current histology teaching strategies, identifying a gap in linking molecular genetics to tissue development, particularly in dental education. For instance, oral histology covers tooth development as a core subject yet often neglects the genetic foundations of odontogenesis. This disconnects risks undermining students’ ability to understand clinically relevant conditions, such as amelogenesis imperfecta, dentinogenesis imperfecta, molar incisor hypomineralization, and tooth agenesis—disorders where genetics play a key role. To address this, we propose a vertically integrated teaching model and a merged approach for teaching where several teaching methods, like flipped classrooms, team-based learning, and personalized digital tools, are designed for institutional curricula. Early pre-clinical exposure to genetic principles, revisited with clinical relevance in later years, can strengthen students’ appreciation of histology’s clinical value. This approach modernizes pedagogy, aligns with students’ preferences for digital learning, and ensures histology retains its central role in shaping competent healthcare professionals. Ultimately, developing multi-modal, genetics-integrated strategies is crucial to revitalizing histology education and fostering a deeper, clinically relevant understanding of human biology. Full article

Background and Clinical Significance: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant soft tissue tumor formerly known as malignant fibrous histiocytoma. In the fifth edition of the WHO classification (2020), UPS is classified as an undifferentiated/unclassifiable sarcoma diagnosed via exclusion. While UPS commonly occurs in the extremities, its incidence in the head and neck region is rare (3%), with only a few reported cases in the oropharynx. Surgical resection is the primary treatment; however, tumors at the tongue base pose significant challenges due to the complex anatomy and the presence of critical neurovascular structures. This case highlights a rare instance of tongue-base UPS successfully treated with transoral videolaryngoscopic surgery (TOVS), demonstrating its feasibility as a minimally invasive approach. Case Presentation: A 68-year-old male presented with pharyngeal discomfort, dysphagia, and nocturnal dyspnea. Clinical examination revealed a pedunculated tumor originating from the left tongue base, occupying the pharyngeal cavity. Imaging studies showed a 5 cm mass without lymph node metastasis. A biopsy confirmed UPS (cT3N0M0). Given the tumor’s characteristics, TOVS was performed using an FK-WO TORS laryngo-pharyngoscope retractor. The tumor was resected with a ≥10 mm margin, achieving complete histological resection. The patient’s dyspnea resolved immediately, and oral intake resumed the next day. No adjuvant radiotherapy was administered, and no recurrence was observed for 50 months. Conclusions: This is the first reported case of UPS of the tongue base successfully resected using TOVS. This minimally invasive approach provides a safe and effective alternative for managing oropharyngeal UPS. Full article

Mature adipocyte-derived dedifferentiated fat (DFAT) cells show proliferative capabilities and multipotency. Given that the buccal fat pad (BFP) serves as a readily available resource for DFAT cell isolation, BFP-derived DFAT (BFP-DFAT) cells are a promising candidate in orofacial tissue engineering. In this research, we assessed the regenerative capacity of the periodontium through autologous BFP-DFAT cell transplantation in adult swine (micro-minipigs; MMPs). The BFP-DFAT cells were transplanted into inflammation-inducing two-walled infrabony periodontal defects located on the mesial of the second mandibular premolar (n = 6). Twelve weeks post-transplantation, a remarkable attachment gain was noted in the DFAT group, based on probing depths and clinical attachment levels. Histological and immunohistochemical analyses indicated new continuous cellular cementum and alveolar bone formation within the created infrabony defect. Well-organized periodontal ligament-like fibers were embedded between newly formed cementum and the alveolar bone. Histometric analysis demonstrated that the DFAT group had a 2.2-fold increase in new alveolar bone length and a 2.2-fold enhancement in vascularization than those in the control group. Except for minor inflammation in the lungs, no teratomas were detected in the recipient MMPs. BFP-DFAT cells significantly enhanced periodontal tissue regeneration, thus representing an optimal source for tissue engineering applications in dentistry. Full article

Cranio-maxillofacial bone defect repair poses significant challenges in oral and maxillofacial surgery due to the complex anatomy of the region and its substantial impact on patients’ physiological function, aesthetic appearance, and quality of life. Inaccurate reconstruction can result in serious complications, including functional impairment and psychological trauma. Traditional methods have notable limitations for complex defects, underscoring the need for advanced computational approaches to achieve high-precision personalized reconstruction. This study presents the Internal Diffusion Network (IDNet), a novel framework that integrates a diffusion model into a standard U-shaped network to extract valuable information from input data and produce high-resolution representations for 3D medical segmentation. A Step-Uncertainty Fusion module was designed to enhance prediction robustness by combining diffusion model outputs at each inference step. The model was evaluated on a dataset consisting of 125 normal human skull 3D reconstructions and 2625 simulated cranio-maxillofacial bone defects. Quantitative evaluation revealed that IDNet outperformed mainstream methods, including UNETR and 3D U-Net, across key metrics: Dice Similarity Coefficient (DSC), True Positive Rate (RECALL), and 95th percentile Hausdorff Distance (HD95). The approach achieved an average DSC of 0.8140, RECALL of 0.8554, and HD95 of 4.35 mm across seven defect types, substantially surpassing comparison methods. This study demonstrates the significant performance advantages of diffusion model-based approaches in cranio-maxillofacial bone defect repair, with potential implications for increasing repair surgery success rates and patient satisfaction in clinical applications. Full article

Guided bone regeneration (GBR) has represented a challenge for clinicians in the past 30 years, and the literature has well described many different surgical options such as d-PTFE membranes, titanium grids, or autogenous bone harvested from the posterior mandible. All of the previously mentioned techniques have shown a high rate of complications but, in the last decade, a new membrane made of xenogenic bone was introduced. Most of the publications regarding its application report very few and mild complications. In this article we will suggest a new application using segmented xenogenic bone sheets instead of autogenous bone to correct severe ridge deformity. Background and Objectives: Xenogenic bone sheets have been studied extensively over the past decade and have proven effective, with a very low rate of complications when used to reconstruct bone atrophies. The technique presented in this paper aims to reduce morbidity, avoid the need for intra-oral graft harvesting, and minimize both surgical time and post-operative discomfort. Materials and Methods: Xenogenic bone sheets of equine origin were used to reconstruct severe 3D bone defects in five patients requiring dental implants. The segmentation of the sheet allowed the operator to rebuild the missing bone walls and achieve optimal anatomy without compromise. Furthermore, using different sizes and thicknesses of the bone sheets allowed safe procedures preventing early exposure of the membranes. CBCT of the defects before and after 8 months of healing were measured with Exocad software to assess the volumetric gain. Histological analysis performed on one site showed integration of the bone lamina and live bone underneath. Results: In all five cases evaluated the ridge deformities were successfully corrected and all patients’ implants have functioned for more than two years to date. The average horizontal bone gain in these five cases was 6.18 mm (±1.19 mm) while the vertical gain was 9.70 mm (±2.39 mm). Conclusions: This new application of flex cortical sheets simplifies the surgical procedure for both operator and patient, reduces morbidity and post-operative complications, and shows promising signs for resolving complex 3D bone reconstructions. Full article

Head and neck cancer encompasses a diverse group of malignant neoplasms originating in regions such as the oral cavity, oropharynx, hypopharynx, larynx, sinonasal cavities, and salivary glands. HNC represents a significant public health challenge, and recent reports indicate an increment in the incidence of HNC in young adults. In 2020, approximately 377,700 new HNC cases and 177,800 HNC-related deaths were reported globally. Major risk factors include tobacco smoking, alcohol consumption, and human papillomavirus (HPV) infections. HNC impacts vital functions such as breathing, swallowing, and speech. Treatments for this type of cancer within this complex anatomy include surgery, radiotherapy, and chemotherapy combinations. Radiotherapy is often an essential component of both curative and palliative HNC treatment, balancing tumor control with the preservation of function and appearance. However, its use can damage adjacent normal tissues, causing acute or chronic toxicity. One complication of HNC irradiation is VF fibrosis, which leads to severe voice impairments, significantly affecting patients’ quality of life. Fibrosis involves excessive and aberrant deposition of extracellular matrix, driven by factors such as TGF-β1 and inflammatory cytokines, which ultimately impair the flexibility and function of VF. Current radiation-induced fibrosis treatments primarily focus on symptom management and include systemic therapies like corticosteroids, anti-inflammatory drugs, and antioxidants. However, these treatments have limited efficacy. Experimental approaches targeting molecular pathways involved in fibrosis are being explored. Given the limitations of these treatments, advancing research is crucial to develop more effective therapeutic strategies that can significantly improve the quality of life for HNC patients, especially those vulnerable to VF fibrosis. Full article

The periodontal ligament (PDL) is a fibrous connective tissue that anchors the tooth-root surface to the alveolar bone with specific orientations. It plays a crucial role in functional restoration, optimal position stabilities, biomechanical stress transmission, and appropriate tissue remodeling in response to masticatory loading conditions. This pilot study explored spatial microarchitectures to promote PDL orientations while limiting mineralized tissue formation. A computer-designed perio-complex scaffold was developed with two parts: (1) PDL-guiding architectures with defined surface topography and (2) a bone region with open structures. After SEM analysis of micropatterned topographies on PDL-guiding architectures, perio-complex scaffolds were transplanted into two-wall periodontal defects in the canine mandible. Despite the limited bone formation at the 4-week timepoint, bone parameters in micro-CT quantifications showed statistically significant differences between the no-scaffold and perio-complex scaffold transplantation groups. Histological analyses demonstrated that the PDL-guiding architecture regulated fiber orientations and facilitated the functional restoration of PDL bundles in immunohistochemistry with periostin and decorin (DCN). The perio-complex scaffold exhibited predictable and controlled fibrous tissue alignment with specific angulations, ensuring spatial compartmentalization for PDL tissues and bone regenerations. These findings highlighted that the perio-complex scaffold could serve as an advanced therapeutic approach to contribute periodontal tissue regeneration and functional restoration in tooth-supporting structures. Full article