Comparative in vitro study of commercially available products for alveolar ridge preservation.

BACKGROUND: Ridge preservation is performed by placing a biocompatible product, following tooth extraction, to maintain bone volume. However, current ridge preservation therapies do not always maintain the volume required for future implant placement. Variations in surgical technique and material selection contribute to determining clinical outcomes. The wide variety of grafting materials available and conflicting efficacy reports make selecting the appropriate graft materials challenging. To investigate how different commercially available ridge preservation products might perform clinically: Helistat (collagen control) (Material 1), OsteoGen Plug (Material 2), Bio-Oss Collagen (Material 3), and J-Bone (native bone) (Material 4) were evaluated. METHODS: These products underwent field emission scanning electron microscopy, microcomputed tomography, helium pycnometry, and infrared spectra analysis. Human osteosarcomas were incubated on products and proliferation was monitored with CCK-8 and visualized with confocal microscopy. Scaffold osteoconductivity was evaluated through the cellular production of proteins osteocalcin, osteonectin, and osteopontin. RESULTS: Results indicated that products varied in porosity and pore interconnectivity. Although Material 3 was chemically similar to Material 4, Material 2 demonstrated significantly better biocompatibility. Functionally, Material 1 and Material 2 elicited higher osteonectin release than Material 3 and Material 4 which suggests the latter products suppress endogenous osteonectin secretion. Furthermore, osteopontin secretion was minimal for all products, while osteocalcin was elevated. This seems to suggest that high levels of mineralization might be deleterious for bone regeneration. CONCLUSIONS: Although all products are marketed as effective preservation products, the results demonstrated high variability in physical, chemical, and biological effects; however, this study suggests a product with higher ratio of collagen to mineral component may have the most desirable effects for the use in alveolar ridge preservation.

An Analysis of the Effectiveness of High-level Disinfection for Surgical Instruments Used by Department of Defense Austere Surgical Teams.

INTRODUCTION: The purpose of this investigation was to evaluate the efficacy of currently employed commercial disinfectants in a simulated austere surgical environment similarly faced by ground surgical teams in forward deployed positions. Severe contamination of traumatic combat wounds along with limitations of operations in austere environments may result in available disinfectants providing inadequate surgical instrument decontamination. MATERIALS AND METHODS: The study consisted of nine experimental groups and two control groups evaluating hemostatic forceps found in kits of ground surgical teams. Hemostats were contaminated in a manner replicating the use in austere wartime surgery, cleaned by manual debridement and soaked in a disinfectant. Initially, instruments were debrided in one of three initial liquids (potable water, sterile water, or potable water with Envirocleanse A) and subsequently treated with one of three terminal disinfectants (Cidex OPA, CaviCide, or Neutral Disinfectant Cleaner). Treated hemostats were placed in sterile wire-closure bags for various storage times and tested for viable bacteria measured by colony-forming units. RESULTS: Our findings indicated that mechanical debridement in water, independent of Envirocleanse A, followed by soaking in any of the three terminal disinfectants achieved a marked reduction in recovered bacteria from hemostats regardless of storage length. Of the three disinfectants tested, Cidex OPA appeared to be the most robust in terms of decontamination, followed by CaviCide and Neutral Disinfectant Cleaner. CONCLUSIONS: This study supports the conclusion that all evaluated disinfectants are capable of rapidly producing instruments with minimal bacterial contaminants when standard sterilization is unavailable. Therefore, when lifesaving surgical intervention must be performed in a deployed environment, austere surgical teams can confidently utilize either product with minimal risk of infection. However, of the disinfectants, Cidex OPA appears to be most effective in reducing bacterial contamination for both rapid and slow turnover of instrument usage, and thus, the disinfectants are recommended for application when sterilization is not available.

Development of Electrospun Chitosan-Polyethylene Oxide/Fibrinogen Biocomposite for Potential Wound Healing Applications.

Normal wound healing is a highly complex process that requires the interplay of various growth factors and cell types. Despite advancements in biomaterials, only a few bioactive wound dressings reach the clinical setting. The purpose of this research was to explore the feasibility of electrospinning a novel nanofibrous chitosan (CS)-fibrinogen (Fb) scaffold capable of sustained release of platelet-derived growth factor (PDGF) for the promotion of fibroblast migration and wound healing. CS-Fb scaffolds were successfully electrospun using a dual-spinneret electrospinner and directly evaluated for their physical, chemical, and biological characteristics. CS-polyethylene/Fb scaffolds exhibited thinner fiber diameters than nanofibers electrospun from the individual components while demonstrating adequate mechanical properties and homogeneous polymer distribution. In addition, the scaffold demonstrated acceptable water transfer rates for wound healing applications. PDGF was successfully incorporated in the scaffold and maintained functional activity throughout the electrospinning process. Furthermore, released PDGF was effective at promoting fibroblast migration equivalent to a single 50 ng/mL dose of PDGF. The current study demonstrates that PDGF-loaded CS-Fb nanofibrous scaffolds possess characteristics that would be highly beneficial as novel bioactive dressings for enhancement of wound healing.

Biocompatibility and antibacterial activity of nitrogen-doped titanium dioxide nanoparticles for use in dental resin formulations.

The addition of antibacterial functionality to dental resins presents an opportunity to extend their useful lifetime by reducing secondary caries caused by bacterial recolonization. In this study, the potential efficacy of nitrogen-doped titanium dioxide nanoparticles for this purpose was determined. Nitrogen doping was carried out to extend the ultraviolet absorbance into longer wavelength blue light for increased biocompatibility. Titanium dioxide nanoparticles (approximately 20-30 nm) were synthesized with and without nitrogen doping using a sol-gel method. Ultraviolet-Visible spectroscopy indicated a band of trap states, with increasing blue light absorbance as the concentration of the nitrogen dopant increased. Electron paramagnetic resonance measurements indicated the formation of superoxide and hydroxyl radicals upon particle exposure to visible light and oxygen. The particles were significantly toxic to Escherichia coli in a dose-dependent manner after a 1-hour exposure to a blue light source (480 nm). Intracellular reactive oxygen species assay demonstrated that the particles caused a stress response in human gingival epithelial cells when exposed to 1 hour of blue light, though this did not result in detectable release of cytokines. No decrease in cell viability was observed by water-soluble tetrazolium dye assay. The results show that nitrogen-doped titanium dioxide nanoparticles have antibacterial activity when exposed to blue light, and are biocompatible at these concentrations.

Genetic deletion of Mst1 alters T cell function and protects against autoimmunity.

Mammalian sterile 20-like kinase 1 (Mst1) is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4+ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE) and protected against collagen-induced arthritis development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.

Inhibition of sphingosine-1-phosphate lyase for the treatment of autoimmune disorders.

During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S1P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression.