Virus-Like Nanostructures For Tuning Immune Response

Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.PubMedWoSScopu

Self-Assembled Peptide Amphiphile Nanofibers And Peg Composite Hydrogels As Tunable Ecm Mimetic Microenvironment

Natural extracellular matrix (ECM) consists of complex signals interacting with each other to organize cellular behavior and responses. This sophisticated microenvironment can be mimicked by advanced materials presenting essential biochemical and physical properties in a synergistic manner. In this work, we developed a facile fabrication method for a novel nanofibrous self-assembled peptide amphiphile (PA) and poly(ethylene glycol) (PEG) composite hydrogel system with independently tunable biochemical, mechanical, and physical cues without any chemical modification of polymer backbone or additional polymer processing techniques to create synthetic ECM analogues. This approach allows noninteracting modification of multiple niche properties (e.g., bioactive ligands, stiffness, porosity), since no covalent conjugation method was used to modify PEG monomers for incorporation of bioactivity and porosity. Combining the self-assembled PA nanofibers with a chemically cross-linked polymer network simply by facile mixing followed by photopolymerization resulted in the formation of porous bioactive hydrogel systems. The resulting porous network can be functionalized with desired bioactive signaling epitopes by simply altering the amino acid sequence of the self-assembling PA molecule. In addition, the mechanical properties of the composite system can be precisely controlled by changing the PEG concentration. Therefore, nanofibrous self-assembled PA/PEG composite hydrogels reported in this work can provide new opportunities as versatile synthetic mimics of ECM with independently tunable biological and mechanical properties for tissue engineering and regenerative medicine applications. In addition, such systems could provide useful tools for investigation of how complex niche cues influence cellular behavior and tissue formation both in two-dimensional and three-dimensional platforms.Wo

Food foreign body injuries

Rationale and aim: The purpose of this study is to acquire a better understanding of Food Foreign Bodies (FFB) injuries in children characterizing the risk of complications and prolonged hospitalization due to food items according to patients' characteristics, circumstances of the accident, Foreign Body (FB) features and FB location, as emerging from the SUSY Safe Web-Registry. Methods: The present study uses data provided by the SUSY Safe Project, a DG SANCO co-funded project started in February 2005, which was aimed at establishing an international registry of cases of Foreign Bodies (FB) injuries in children aged 0-14 years. The analysis was carried out on injuries due to a food item.FB location was reported according to ICD9-CM code: ears (ICD931), nose (ICD932), pharynx and larynx (ICD933) trachea, bronchi and lungs (ICD934), mouth, esophagus and stomach (ICD935).Age and gender injury distributions were assessed. Data regarding adult supervision and activity before injury were also evaluated. FBs which most frequently cause complications were identified. The association between children age, adult presence, object characteristics and hospitalization/complications was computed using unweighted odds ratios and the related 95% confidence intervals. Results: 16,878 FB injuries occurred in children aged 0-14 years have been recorded in the SUSY Safe databases. FB type was specified in 10,564 cases; among them 2744 (26%) were due to a food item. FB site was recorded in 1344 cases: FB was located in the ears in 99 patients, while 1140 occurred in the upper and lower respiratory tract; finally, 105 food items were removed from mouth, esophagus and stomach. Complications occurred in 176 cases and the most documented was pulmonary or bronchial infections (23%) followed emphysema or atelectasis and by and asthma (7%). Bones were the commonest retrieved FFB encountered in this study, while nuts seem to be the FFB most frequently associated to complications. Conclusions: On the basis of this study we make the strong recommendation that parents should be adequately educated and provide age-appropriate food to their children and be present in order to supervise them during eating especially during a critical period ranging from 2 to 3 years of age