Development and characterization of highly stable silver nanoparticles as novel potential antimicrobial agents for wound healing hydrogels

Recurrent microbial infections are a major cause of surgical failure and morbidity. Wound healing strategies based on hydrogels have been proposed to provide at once a barrier against pathogen microbial colonization, as well as a favorable environment for tissue repair. Nevertheless, most biocompatible hydrogel materials are more bacteriostatic than antimicrobial materials, and lack specific action against pathogens. Silver-loaded polymeric nanocomposites have efficient and selective activity against pathogenic organisms exploitable for wound healing. However, the loading of metallic nanostructures into hydrogels represents a major challenge due to the low stability of metal colloids in aqueous environments. In this context, the aim of the present study was the development of highly stable silver nanoparticles (AgNPs) as novel potential antimicrobial agents for hyaluronic acids hydrogels. Two candidate stabilizing agents obtained from natural and renewable sources, namely cellulose nanocrystals and ulvan polysaccharide, were exploited to ensure high stability of the silver colloid. Both stabilizing agents possess inherent bioactivity and biocompatibility, as well as the ability to stabilize metal nanostructures thanks to their supramolecular structures. Silver nitrate reduction through sodium borohydride in presence of the selected stabilizing agents was adopted as a model strategy to achieve AgNPs with narrow size distribution. Optimized AgNPs stabilized with the two investigated polysaccharides demonstrated high stability in phosphate buffer saline solution and strong antimicrobial activity. Loading of the developed AgNPs into photocrosslinked methacrylated hyaluronic acid hydrogels was also investigated for the first time as an effective strategy to develop novel antimicrobial wound dressing materials.This research was supported by the Portuguese Foundation for Science and Technology (FCT) under the projects PTDC/BII-BIO/28870/2017 and POCI-01-0145-FEDER-007038 (UID/Multi/ 50026/2013), and by the European Regional Development Fund (FEDER) through the “COMPETE”— Operational Program for Competitiveness factors (FCOMP-01-0124-FEDER-028120). A.R.F. thanks FCT through the Post-Doctoral scholarship SFRH/BPD/100760/2014

Optimized electro- and wet-spinning techniques for the production of polymeric fibrous scaffolds loaded with bisphosphonate and hydroxyapatite

This research activity was aimed at the development of composite bioactive scaffolds made of biodegradable three-arm branched-star poly(ε-caprolactone) (∗PCL), hydroxyapatite nanoparticles (HNPs) and clodronate (CD), a bisphosphonate that has demonstrated efficacy in the treatment of various bone diseases and as an anti-inflammatory drug. During the experimental work, the processing conditions for the fabrication of fibrous meshes, by either electrospinning or wetspinning, were optimized. Stemming from a previous research activity on electrospinning of ∗PCL, ∗PCL/HNPs 3D meshes were developed, evaluating the influence of fabrication parameters on the fibres’ morphology. By exploiting the binding affinity of bisphosphonates for hydroxyapatite, a methodology was set up for obtaining a physical linkage between CD and HNPs, with the aim of having a dual bioactive system loaded into ∗PCL fibrous mats. Fibres loaded with either CD or CD–HNP particles were thus produced and analysed by scanning electron microscopy for their morphology and by energy dispersive X-ray spectroscopy for their elemental compositionThis work was done within the framework of the European Network of Excellence 'EXPERTISSUES', Project No. NMP3-CT-2004-500283. Professor Ramani Narayan of Michigan Biotechnology Institute and Dr Fabio Neggiani of Abiogen Pharma-Pisa are acknowledged for supplying *PCL and CD, respectively

Working directly with probabilities in quantum field theory

We present a novel approach to computing transition probabilities in quantum field theory, which allows them to be written directly in terms of expectation values of nested commutators and anti-commutators of field operators, rather than squared matrix elements. We show that this leads to a diagrammatic expansion in which the retarded propagator plays a dominant role. As a result, one is able to see clearly how faster-than-light signalling is prevented between sources and detectors. Finally, we comment on potential implications of this approach for dealing with infra-red divergences

Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs

Development of silk-based scaffolds for tissue engineering of bone from human adipose derived stem cells

Silk fibroin is a potent alternative to other biodegradable biopolymers for bone tissue engineering (TE), because of its tunable architecture and mechanical properties, and its demonstrated ability to support bone formation both in vitro and in vivo. In this study, we investigated a range of silk scaffolds for bone TE using human adipose-derived stem cells (hASCs), an attractive cell source for engineering autologous bone grafts. Our goal was to understand the effects of scaffold architecture and biomechanics and use this information to optimize silk scaffolds for bone TE applications. Silk scaffolds were fabricated using differ- ent solvents (aqueous vs. hexafluoro-2-propanol (HFIP)), pore sizes (250–500 um vs. 500–1000 um) and structures (lamellar vs. spherical pores). Four types of silk scaffolds combining the properties of interest were systematically compared with respect to bone tissue outcomes, with decellularized trabecular bone (DCB) included as a ‘‘gold standard’’. The scaffolds were seeded with hASCs and cultured for 7 weeks in osteogenic medium. Bone formation was evaluated by cell proliferation and differentiation, matrix production, calcification and mechanical properties. We observed that 400–600 um porous HFIP-derived silk fibroin scaffold demonstrated the best bone tissue formation outcomes, as evidenced by increased bone protein production (osteopontin, collagen type I, bone sialoprotein), enhanced calcium deposition and total bone volume. On a direct comparison basis, alkaline phosphatase activity (AP) at week 2 and new calcium deposition at week 7 were comparable to the cells cultured in DCB. Yet, among the aqueous- based structures, the lamellar architecture induced increased AP activity and demonstrated higher equi- librium modulus than the spherical-pore scaffolds. Based on the collected data, we propose a conceptual model describing the effects of silk scaffold design on bone tissue formation.FCT: SFRH/BD/42316/2007NIH: DE161525 and EB0252

Punishment in the Frame: Rethinking the History and Sociology of Art

Images of punishment have featured prominently in Western art and this article explores what might be learnt from studying such pictures of suffering. It seeks to develop an approach to the visual that avoids both the essentialism of art history and the reductionism of sociology by offering a rethinking of the relationships between the two. It begins by setting out the current state of the sociology of art, before discussing ‘new’ art histories that are inspired by social analysis. It then concentrates on how images of punishment have featured in Western art. This substantive material provides a rich resource to understand the force of representation and offers an opportunity to develop an aesthetic sociology that avoids some of the problems identified in the article. The approach developed in the second part is one that seeks to elaborate an aesthetic sociology that combines a historical sensitivity to images with the analytical concerns of social science. It strives to extend the art historian Michael Baxandall’s writings toward more sociological interpretations of visual analysis

Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio