David Kirmayer

[This corrects the article DOI: 10.1155/2019/2348146.].

Large bone defects pose an unsolved challenge for orthopedic surgeons. Our group has previously reported the construction of a barrier membrane made of ammoniomethacrylate copolymer USP (AMCA), which supports the adhesion, proliferation, and osteoblastic differentiation of human mesenchymal stem cells (hMSCs). In this study, we report the use of AMCA membranes to seclude critical segmental defect (~1.0 cm) created in the middle third of rabbit radius and test the efficiency of bone regeneration. Bone regeneration was assessed by radiography, biweekly for 8 weeks. The results were verified by histology and micro‐CT at the end of the follow‐up. The AMCA membranes were found superior to no treatment in terms of new bone formation in the defect, bone volume, callus surface area normalized to total volume, and the number of bone trabeculae, after eight weeks. Additional factors were then assessed, and these included the addition of simvastatin to the membrane, coating the membrane with human MSC, and a combination of those. The addition of simvastatin to the membranes demonstrated a stronger effect at a similar radiological follow‐up. We conclude that AMCA barrier membranes per se and simvastatin delivered in a controlled manner improve bone regeneration outcome.

Enterococcus faecalis is a bacterium frequently isolated after failed root canal therapy. This study analyzed the antibacterial and antibiofilm effects in vitro of sustained-release fillers (SRF) containing cetylpyridinium chloride (CPC) against vancomycin resistant E. faecalis. First, the solidification capability was tested by introducing liquid SRF into phosphate buffered saline, followed by 30 s of vortexing. The antimicrobial effects of SRF-CPC against static monospecies biofilms were analyzed with a metabolic assay. Inhibition of biofilm formation was tested by exposing daily refreshed E. faecalis suspensions to SRF-CPC for 9 weeks. To evaluate the effects of SRF-CPC against preformed biofilms, biofilms were grown for 1, 3 and 7 days, and then treated with SRF-CPC for 24 h. Biofilm kill time was tested by applying SRF-CPC to a 3-day-old biofilm and measuring its viability at different time points. All experiments were compared to Placebo SRFs and to untreated control biofilms. Data were analyzed with two-way ANOVA followed by Tukey’s test. Results were considered significant at P < 0.05. The liquid SRF solidified within seconds and no structural changes were observed after 30 s of vortexing at maximum speed. SRF-CPC inhibited E. faecalis biofilm formation for 7 weeks and significantly reduced its viability in weeks 8 and 9. Mature biofilms grown for 1, 3 and 7 days were destructed by SRF-CPC in less than 24 h. Fifty percent of a 3-day-old biofilm was destructed in 2 h and complete destruction occurred in less than 12 h. (P < 0.05 in all cases, compared to SRII-Placebo). SRF-CPC’s physical properties and long-lasting anti-biofilm effects make it a promising coadjuvant medication for endodontic therapy.

Enterococcus faecalis is the most commonly recovered species from failed root canal treatments. In this study, we tested the capability of a novel intracanal sustained-release filler (SRF) containing cetylpyridinium chloride (CPC) to disinfect dentinal tubules of segmented human tooth specimens. Human dental root specimens were infected with E. faecalis V583 for 3 weeks in a static environment. The tested intracanal medicaments were SRF-CPC and calcium hydroxide (CH). Each medicament was introduced into the canal of the dental specimen and incubated for 7 days. The bacteriological samples were taken by shaving the dentine surrounding the root canal with dental burs ranging in size from ISO 014-020. The obtained dentine powder was collected in test tubes containing phosphate-buffered saline, sonicated, and plated on agar plates. Colony-forming units were counted after 48 h of incubation. Random specimens were also examined under confocal laser scanning microscopy and scanning electron microscopy. A statistical difference was found in the bacterial counts obtained from all layers of infected dentin between the control and the SRF-CPC groups. CH reduced bacterial viability significantly only in the first layer of the infected dentin, up to 150 μm into the dentinal tubules. CLSM images showed that SRF-CPC killed most bacteria throughout the infected dentin up to 700 μm of penetration. SEM images demonstrated the adhesion ability of SRF-CPC to the dentinal wall. In conclusion, SRF-CPC is a potential intracanal medicament for disinfecting dentinal tubules.

Myiasis is a major disease condition in human and veterinary medicine. Domestic, free-ranging, and zoo-housed animals can be severely affected by myiasis. Depending on case severity, multiple treatment episodes may be indicated and can lead to recurrent capturing, handling stress, and anesthetics, all of which increase the risk of adverse responses (including death) individually and also in the herd. As an insecticide, ivermectin is often used for larval control. A total of 28 individual myiasis cases were retrospectively evaluated, out of which 11 cases were also treated using an ivermectin sustained-release varnish (SRV). The clinical outcome of all cases was assessed and the results suggest that the use of a topical ivermectin SRV (with or without concurrent injectable ivermectin) can reduce handling and treatments, has no adverse effects, and has minimal recurrence of the disease when compared with cases treated without it.

Sirolimus (rapamycin) is a mammalian target of rapamycin pathway blocker. The efficacy of sirolimus is currently studied for its antiproliferative properties in various malignancies and particularly in squamous cell carcinoma and other oral disorders. Topical application at the oral cavity can augment sirolimus availability at the site of action by increasing sirolimus levels in saliva and hence efficacy, along with improved safety (low levels in the blood to avoid side effects) and compliance. Our purpose was to evaluate the release profile and safety of a topical sirolimus sustained-release varnish drug delivery system. Sirolimus sustained-release varnish drug delivery system containing a total of 0.5 mg of the drug was applied to nine healthy male volunteers. Saliva and blood levels were determined utilizing mass spectrometry and chemiluminescent microparticle immunoassay, respectively. The prolonged release profile and safety were evaluated for the oral topical delivery system. After the application of the drug delivery system, a sustained-release profile was observed in the oral cavity. We have measured moderate sirolimus levels for up to 12 h. The safety was confirmed, and systemic sirolimus blood levels were negligible. After an application of sirolimus sustained-release varnish drug delivery system, prolonged drug levels can be achieved in the saliva. The oral topical sirolimus concentrations were potentially therapeutic along with minimal systemic exposure. These results broaden the potential clinical use of sustained-release oral topical rapalogs.