Chitosan/copper nanocomposites: Correlation between electrical and antibacterial properties.

Correlation between electrical and antibacterial properties of chitosan/copper nanocomposites (CS/CuNPs) is investigated. We aim at achieving the minimum CuNPs concentration in a CS-matrix while keeping high antibacterial activity. UV-vis, TEM and XRD measurements confirms the formation of polygonal metallic CuNPs (ca. 30-50 nm). Interactions between NH2/OH groups of CS and CuNPs were determined by FTIR and XPS suggesting Cu chelation-induced mechanism during the CuNPs formation. DC electrical conductivity measurements reveals a percolation threshold at CuNPs volumetric concentration of ca. 0.143%. Antibacterial assays against Gram-positive bacteria and DC measurements helps correlate the antibacterial potency to the electron transfer between the negatively charged bacteria and CuNPs. Our study suggests that nanocomposite's maximum antibacterial activity is obtained below the electrical percolation threshold at extremely low CuNPs concentrations; this fact may prove useful in the design of nontoxic nanocomposites for biomedical applications.

(Chitosan-g-glycidyl methacrylate)-xanthan hydrogel implant in Wistar rats for spinal cord regeneration.

This work reports the results of in vivo assays of an implant composed of the hydrogel Chitosan-g-Glycidyl Methacrylate-Xanthan [(CTS-g-GMA)-X] in Wistar rats. Degradation kinetics of hydrogels was assessed by lysozyme assays. Wistar rats were subjected to laminectomy by cutting the spinal cord with a scalpel. After the surgical procedure, hydrogels were implanted in the injured zone (level T8). Somatosensory evoked potentials (SEPs) obtained by electric stimulation onto periphery nerves were registered in the corresponding central nervous system (CNS) areas. Rats implanted with the biomaterials showed a successful recovery compared with the non-implanted rats after 30days. Lysozyme, derived from egg whites, was used for in vitro assays. This study serves as the basis for testing the biodegradability of the hydrogels (CTS-g-GMA)-X that is promoted by enzymatic hydrolysis. Hydrogels' hydrolysis was studied via lysozyme kinetics at two pH values, 5 and 7, under mechanical agitation at 37°C. Results show that our materials' hydrolysis is slower than pure CTS possibly due to the steric hindrance imposed by the GMA grafting of functionalization. This hydrolysis helps degrade the biomaterial and at the same time it provides support for spinal cord recovery. Combination of these results may prove useful in the use of these hydrogels as scaffolds for cells proliferation and their application as implants in living organisms.

Deficiency of Kruppel-like factor KLF4 in myeloid-derived suppressor cells inhibits tumor pulmonary metastasis in mice accompanied by decreased fibrocytes.

The importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) bearing monocyte markers in tumor metastasis has been well established. Recently, it was reported that these cells possess phenotypic plasticity and differentiate into fibrocytes, very distinct cells that are precursors of tumorigenic myofibroblasts. However, the importance of this transdifferentiation in tumor metastasis has not been explored. Here, we describe the role of MDSC-derived fibrocytes in tumor metastasis that is regulated by Kruppel-like factor 4 (KLF4), a transcription factor that is critical to monocyte differentiation and to promotion of cancer development. Using mouse metastasis models of melanoma and breast cancer, we found that KLF4 knockout was associated with significantly reduced pulmonary metastasis, which was accompanied by decreased populations of MDSCs, fibrocytes and myofibroblasts in the lung. Cause-effect studies by adoptive transfer revealed that KLF4 deficiency in MDSCs led to significantly reduced lung metastasis that was associated with fewer MDSC-derived fibrocytes and myofibroblasts. Mechanistically, KLF4 deficiency significantly compromised the generation of fibrocytes from MDSCs in vitro. During this process, KLF4 expression levels were tightly linked with those of fibroblast-specific protein-1 (FSP-1), deficiency of which resulted in no metastasis in mice as has been previously reported. In addition, KLF4 bound directly to the FSP-1 promoter as determined by chromatin immunoprecipitation and overexpression of KLF4 increased the FSP-1 promoter activities. Taken together, our results suggest that MDSCs not only execute their immunosuppressive function to promote metastatic seeding as reported before, but also boost metastatic tumor growth after they adopt a fibrocyte fate. Therefore, KLF4-mediated fibrocyte generation from MDSCs may represent a novel mechanism of MDSCs contributing to tumor metastasis and supports the feasibility of inhibiting KLF4 or FSP-1 to prevent tumor metastasis.

Synthesis and characterization of a hybrid (chitosan-g-glycidyl methacrylate)-xanthan hydrogel.

This work reports the synthesis and characterization of a new material obtained by mixing the hybrid natural-synthetic chitosan-g-glycidyl methacrylate (CTS-g-GMA) biopolymer and xanthan gum (X). All materials were characterized by infrared spectroscopy (FTIR), X-ray diffraction, and thermal analysis (DSC and TGA) and the results were contrasted with those of the precursor materials. The swelling index of the hydrogels decreases when the GMA mass percentage increases. The X-ray diffraction patterns show that the hybrid hydrogels are amorphous in contrast to chitosan (CTS), which is semi-crystalline. FTIR analysis confirms the existence of physical interactions among constituents. Rheological properties, η, G', and G", were determined as a function of flow allowing one to conclude that (CTS-g-GMA)-X behaves as physical hydrogel. Additionally, we report viability of fibroblasts when cultured onto the synthesized hydrogels. This study shows that these hydrogels support cell viability and have potential for use in biomedical engineering applications.

Hybrid natural-synthetic chitosan resin: thermal and mechanical behavior.

Poly(methyl methacrylate) (PMMA) is one of the most commonly plastics used as dental-base material, due to its good biological compatibility and mechanical properties. Chitosan has wide application in chemical, biochemical and biomedical fields of research. In this work, chitosan (CTS) was functionalized with glycidyl methacrylate (GMA), to ease a further reaction with MMA. The resulting co-polymer was finally blended with PMMA and poly(butyl acrylate) PBA which works as a damper, the polymers were cured by UV to obtain the final resin. Characterization of UV-cured resins was carried out by thermal measurements, X-ray diffraction, atomic force microscopy (AFM), micro and nanoindentation, water absorption and elution in water. As a result a higher thermal stability of the final resin compared with the precursor co-polymer ((CTS-GMA)-g-PMMA) was obtained. The resin presented roughness in the nanometer scale and nanoparticles embedded in the acrylic matrix producing a tough material. However, XRD measurements show that all materials are in an amorphous state. Values of hardness and elastic modulus results were very near to those of the dentine. The results of elution in water of the tested resin samples show them as clinically acceptable as a dental base material.

Goodness-of-fit of the distribution of time-to-first-occurrence in recurrent event models.

Imperfect repair models are a class of stochastic models that deal with recurrent phenomena. This article focuses on the Block, Borges, and Savits (1985) age-dependent minimal repair model (the BBS model) in which a system that fails at time t undergoes one of two types of repair: with probability p(t), a perfect repair is performed, or with probability 1-p(t), a minimal repair is performed. The goodness-of-fit problem of interest concerns the initial distribution of the failure ages. In particular, interest is on testing the null hypothesis that the hazard rate function of the time-to-first-event-occurrence, lambda(.), is equal to a prespecified hazard rate function lambda 0(.). This paper extends the class of hazard-based smooth goodness-of-fit tests introduced in Peña (1998a) to the case where data accrual is from a BBS model. The goodness-of-fit tests are score tests derived by reformulating Neyman's idea of smooth tests in terms of hazard functions. Omnibus as well as directional tests are developed and simulation results are presented to illustrate the sensitivities of the proposed tests for certain types of alternatives.

Dynamic reliability models with conditional proportional hazards.

A dynamic approach to the stochastic modelling of reliability systems is further explored. This modelling approach is particularly appropriate for load-sharing, software reliability, and multivariate failure-time models, where component failure characteristics are affected by their degree of use, amount of load, or extent of stresses experienced. This approach incorporates the intuitive notion that when a set of components in a coherent system fail at a certain time, there is a 'jump' from one structure function to another which governs the residual lifetimes of the remaining functioning components, and since the component lifetimes are intrinsically affected by the structure function which they constitute, then at such a failure time there should also be a jump in the stochastic structure of the lifetimes of the remaining components. For such dynamically-modelled systems, the stochastic characteristics of their jump times are studied. These properties of the jump times allow us to obtain the properties of the lifetime of the system. In particular, for a Markov dynamic model, specific expressions for the exact distribution function of the jump times are obtained for a general coherent system, a parallel system, and a series-parallel system. We derive a new family of distribution functions which describes the distributions of the jump times for a dynamically-modelled system.