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Nanodiamond–Gutta Percha Composite Biomaterials for Root Canal Therapy

Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprising blood vessels and nerve tissue, decontaminating residually infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously composed of dental pulp. Gutta percha (GP) is typically used as the filler material, as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and microcomputed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path toward NDGP implementation in future endodontic therapy for improved treatment outcomes.

Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease

Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology.

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in mice. A Randomized, Prospective, Controlled Animal Study

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen‐induced arthritis (CIA), and CIA‐ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freunds adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks. ONJ indices were measured by micro‐CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA‐ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA‐ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA‐ZA but more extensively in CIA‐ZA animals, indicating more severe ONJ. CIA and CIA‐ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA‐ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development.

Zoledronate Impairs Socket Healing after Extraction of Teeth with Experimental Periodontitis

Osteonecrosis of the jaws (ONJ) is a rare but severe complication of antiresorptive medications, such as bisphosphonates, used in the treatment of bone malignancy or osteoporosis. Tooth extraction and dental disease have been strongly associated with ONJ development. Here, we investigated molecular and cellular markers of socket healing after extraction of healthy or teeth with experimental periodontitis (EP) in Wistar-Han rats treated with zoledronic acid (ZA). We included 4 experimental groups: vehicle-treated animals with extraction of healthy teeth or teeth with ligature-induced EP and ZA-treated animals with extraction of healthy teeth or teeth with EP. Animals were pretreated with vehicle or ZA for a week, and EP was induced. Four weeks later, the second maxillary molars were extracted; sockets were allowed to heal for 4 wk; animals were euthanized; and maxillae were isolated. Radiographically, extraction sockets in groups 1, 2, and 3 demonstrated normal healing. Contrary incomplete socket healing was noted after extraction of teeth with EP in ZA-treated rats of group 4. Histologically, persistent inflammation and extensive osteonecrosis were seen in group 4. Disorganization of the collagen network, collagen type III predominance, and lack of collagen fiber insertion in the necrotic bone were associated with impaired socket healing. Cells positive for MMP-9, MMP-13, and α-SMA expression were present at the areas of epithelial invagination and adjacent to osteonecrotic bone. Importantly, human biopsies from patients with ONJ showed similar findings. Our data emphasize the importance of dental disease and tooth extraction in ONJ pathogenesis and help delineate an altered profile in wound-healing markers during ONJ development.

Radiographic predictors of bone exposure in patients with stage 0 medication-related osteonecrosis of the jaws

OBJECTIVE The aim of this study was to explore the radiographic appearance of stage 0 medication-related osteonecrosis of the jaws (MRONJ) and examine 5 radiographic parameters (trabecular sclerosis, cortical erosion, periosteal reaction, sequestration, and crater-like defect) as predictors of progression to bone exposure. STUDY DESIGN Twenty-three patients with a history of antiresorptive therapy, no bone exposure, and nonspecific signs and symptoms were included. Intraoral photographs, panoramic and cone beam computed tomography (CBCT) images at initial visit, and follow-up intraoral photographs were reviewed. Three patients had dental disease (DD), 10 patients with stage 0 MRONJ did not progress to bone exposure (NBE), and 10 patients progressed to bone exposure (BE). Radiographic parameters were scored as absent (0), localized (1), or extensive (2), and their sum formed the composite radiographic index (CRI). RESULTS DD patients demonstrated minimal radiographic findings, and their CRI was significantly lower than that of NBE and BE patients. Additionally, BE patients demonstrated a higher radiographic index compared with NBE patients. Intriguingly, sequestration was observed in the initial CBCT of 9 (90%) of 10 BE patients, whereas 80% of NBE patients showed absence of sequestration at initial CBCT examination. CONCLUSIONS CBCT imaging can aid in the differentiation of stage 0 MRONJ from dental disease. Radiographic sequestration at initial presentation can serve as a predictor of future bone exposure in patients with stage 0 MRONJ.

Nonsurgical Management of Medication-Related Osteonecrosis of the Jaws Using Local Wound Care

PURPOSE Medication-related osteonecrosis of the jaws (MRONJ) is a known complication of antiresorptive medications with surgical and nonsurgical treatment options. The aim of this study was to evaluate the effectiveness of nonsurgical therapy using local wound care on management of MRONJ lesions. MATERIALS AND METHODS The authors conducted a retrospective cohort study of patients who presented to the University of California-Los Angeles School of Dentistry Oral and Maxillofacial Surgery Clinic for evaluation and treatment of MRONJ. The primary predictor variable was wound care score; secondary predictors were demographics (age, gender), anatomic location, primary condition, and type and time of antiresorptive treatment. Outcomes assessed were disease resolution and time to disease resolution. Statistical analysis was carried out using the Spearman correlation for continuous and ordinal variables or the χ2 test for categorical variables. Time-to-event statistics and Cox proportional hazards models were calculated; a Kaplan-Meier plot was generated to assess time to healing. RESULTS One hundred six patients with 117 MRONJ lesions were treated using local wound care; complete disease resolution was observed 71% of lesions, with an additional 22% of lesions undergoing disease improvement. Wound care score was statistically associated with disease resolution and time to resolution, whereas demographics, anatomic site, condition, and type and time of antiresorptive treatment had no effect on resolution. CONCLUSION Local wound care increased the likelihood of MRONJ resolution and decreased the time to disease resolution. This strategy can be used in patients who cannot undergo surgery and should be implemented in all patients with MRONJ lesions who are managed nonsurgically.

Clinically Relevant Doses of Sclerostin Antibody Do Not Induce Osteonecrosis of the Jaw (ONJ) in Rats with Experimental Periodontitis: SCLEROSTIN ANTIBODY DOES NOT INDUCE ONJ

Antiresorptive agents, such as bisphosphonates and denosumab, are frequently used for the management of osteoporosis. Indeed, both medications decrease the risk of osteoporotic fractures; however, these medications are associated with rare but potentially severe side effects, such as osteonecrosis of the jaw (ONJ). ONJ, defined as an area of exposed bone in the maxillofacial region that lasts for 8 weeks, often presents with significant pain and infection and can lead to serious complications. Interestingly, other treatments for osteoporosis have been developed, such as antibodies against the osteocyte‐secreted protein, sclerostin. Sclerostin functions to inhibit the Wnt signaling cascade, leading to inhibition of bone formation. In clinical trials, a sclerostin antibody (romosozumab, Amgen Inc., UCB Brussels) increases bone formation and lowers the risk of osteoporotic fractures. However, in conjunction with increased osteoblastic activity, a reduction in bone resorption markers is observed. This antiresorptive effect raises the concern of possible ONJ development in patients treated with sclerostin antibodies. Here, utilizing ligature‐induced experimental periodontitis (EP), we evaluated the effects of sclerostin inhibition on the development of ONJ‐like lesions in ovariectomized rats. Beginning 8 weeks post‐ovariectomy, rats were treated for 22 weeks with weekly injections of vehicle (Veh), 200 μg/kg zoledronic acid (ZA), a potent bisphosphonate at 100‐fold the osteoporosis dose, or 5 mg/kg sclerostin antibody (Scl‐Ab) at the osteoporotic dose. EP was initiated at week 12 and maintained for the remainder of the study. Scl‐Ab treatment transiently increased serum P1NP, a bone formation marker, increased BV/TV, and decreased eroded surfaces in lumbar vertebrae. ZA‐treated rats developed histologic features of ONJ, whereas Veh‐treated controls did not. Scl‐Ab animals lost less periodontal bone in sites with EP. However, these animals presented with no histologic signs of ONJ. In conclusion, sclerostin inhibition enhanced structural bone parameters, without inducing ONJ‐like lesions, in ovariectomized rats with EP.

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Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprising blood vessels and nerve tissue, decontaminating residually infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously composed of dental pulp. Gutta percha (GP) is typically used as the filler material, as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and microcomputed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path toward NDGP implementation in future endodontic therapy for improved treatment outcomes.

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Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprising blood vessels and nerve tissue, decontaminating residually infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously composed of dental pulp. Gutta percha (GP) is typically used as the filler material, as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and microcomputed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path toward NDGP implementation in future endodontic therapy for improved treatment outcomes.

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Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprising blood vessels and nerve tissue, decontaminating residually infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously composed of dental pulp. Gutta percha (GP) is typically used as the filler material, as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and microcomputed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path toward NDGP implementation in future endodontic therapy for improved treatment outcomes.