Tailoring gelation mechanisms for advanced hydrogel applications

Hydrogels are one of the most commonly explored classes of biomaterials. Their chemical and structural versatility has enabled their use across a wide range of applications, including tissue engineering, drug delivery, and cell culture. Hydrogels form upon a sol–gel transition, which can be elicited by different triggers designed to enable precise control over hydrogelation kinetics and hydrogel structure. The chosen hydrogelation trigger and chemistry can have a profound effect on the success of the targeted application. In this Progress Report, a critical overview of recent advances in hydrogel design is presented, with a focus on the available strategies used to trigger the formation of hydrogel networks (e.g., temperature, light, ultrasound). These triggers are presented within a new classification system, and their suitability for six key hydrogel‐based applications is assessed. This Progress Report is intended to guide trigger selection for new hydrogel applications and inspire the rational design of new hydrogelation trigger mechanisms

Drilling polymeric matrix composites

This chapter presents the basics of drilling of polymeric matrix composites (PMCs). PMCs are becoming widely used in the manufacturing of products where a high mechanical strength must be accompanied by a low weight. However, the machining of PMCs implies coping with problems that are not encountered when machining other materials. Drilling is a particularly critical operation for PMCs laminates because the large concentrated forces generated can lead to widespread damage. This damage causes aesthetic problems but, more importantly, may compromise the mechanical properties of the finished part

Anal canal duplication in an 11-year-old-child

Anal canal duplication (ACD) is the least frequent digestive duplication. Symptoms are often absent but tend to increase with age. Recognition is, however, important as almost half of the patients with ACD have concomitant malformations. We present the clinical history of an eleven-year-old girl with ACD followed by a review of symptoms, diagnosis, treatment, and prognosis based on all the reported cases in English literature

Spatial patterns of excitation at tissue and whole organ level due to early afterdepolarizations

Early after depolarizations (EAD) occur in many pathological conditions, such as congenital or acquired channelopathies, drug induced arrhythmias, and several other situations that are associated with increased arrhythmogenicity. In this paper we present an overview of the relevant computational studies on spatial EAD dynamics in 1D, 2D, and in 3D anatomical models and discuss the relation of EADs to cardiac arrhythmias. We also discuss unsolved problems and highlight new lines of research in this area

Dynamical anchoring of distant Arrhythmia Sources by Fibrotic Regions via Restructuring of the Activation Pattern

Rotors are functional reentry sources identified in clinically relevant cardiac arrhythmias, such as ventricular and atrial fibrillation. Ablation targeting rotor sites has resulted in arrhythmia termination. Recent clinical, experimental and modelling studies demonstrate that rotors are often anchored around fibrotic scars or regions with increased fibrosis. However the mechanisms leading to abundance of rotors at these locations are not clear. The current study explores the hypothesis whether fibrotic scars just serve as anchoring sites for the rotors or whether there are other active processes which drive the rotors to these fibrotic regions. Rotors were induced at different distances from fibrotic scars of various sizes and degree of fibrosis. Simulations were performed in a 2D model of human ventricular tissue and in a patient-specific model of the left ventricle of a patient with remote myocardial infarction. In both the 2D and the patient-specific model we found that without fibrotic scars, the rotors were stable at the site of their initiation. However, in the presence of a scar, rotors were eventually dynamically anchored from large distances by the fibrotic scar via a process of dynamical reorganization of the excitation pattern. This process coalesces with a change from polymorphic to monomorphic ventricular tachycardia.Comment: 16 pages, 7 figure

Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis

In human cells, the RIPK1-RIPK3-MLKL-PGAM5-Drp1 axis drives tumor necrosis factor (TNF)-induced necroptosis through mitochondrial fission, but whether this pathway is conserved among mammals is not known. To answer this question, we analyzed the presence and functionality of the reported necroptotic axis in mice. As in humans, knockdown of receptorinteracting kinase-3 (RIPK3) or mixed lineage kinase domain like (MLKL) blocks TNF-induced necroptosis in L929 fibrosarcoma cells. However, repression of either of these proteins did not protect the cells from death, but instead induced a switch from TNF-induced necroptosis to receptor-interacting kinase-1 (RIPK1) kinase-dependent apoptosis. In addition, although mitochondrial fission also occurs during TNF-induced necroptosis in L929 cells, we found that knockdown of phosphoglycerate mutase 5 (PGAM5) and dynamin 1 like protein (Drp1) did not markedly protect the cells from TNF-induced necroptosis. Depletion of Pink1, a reported interactor of both PGAM5 and Drp1, did not affect TNF-induced necroptosis. These results indicate that in these murine cells mitochondrial fission and Pink1 dependent processes, including Pink-Parkin dependent mitophagy, apparently do not promote necroptosis. Our data demonstrate that the core components of the necrosome (RIPK1, RIPK3 and MLKL) are crucial to induce TNF-dependent necroptosis both in human and in mouse cells, but the associated mechanisms may differ between the two species or cell types

Common incidental findings on sacroiliac joint MRI in children clinically suspected of juvenile spondyloarthritis

PURPOSE: To determine the prevalence of incidental findings on sacroiliac (SI) joint MRI in children clinically suspected of Juvenile Spondyloarthritis (JSpA). METHODS: In this retrospective multi-center study of 540 children clinically suspected of JSpA who underwent MRI of SI joints from February 2012 to May 2018, the prevalence of sacroiliitis and other incidental findings was recorded. RESULTS: In 106/540 (20 %) children MRI features of sacroiliitis were present. In 228 (42 %) patients MRI showed at least one incidental finding other than sacroiliitis. A total of 271 abnormal findings were reported. The most frequent incidental findings were at lumbosacral spine (158 patients, 29 %) and hip (43 patients, 8 %). The most common incidental finding was axial degenerative changes, seen in 94 patients (17 %). Other less frequent pathologies were: simple (bone) cyst in 15 (2,8 %) patients; enthesitis/tendinitis in 16 (3 %) patients; non-specific focal bone marrow edema (BME) away from SI joints in 10 (1,9 %) patients; ovarian cysts in 7 (1,3 %) patients; BME in the course of chronic recurrent multifocal osteomyelitis (CRMO) in 4 (0,7 %) patients; muscle pathology in 4 (0,7%) patients; benign tumors in 3 (0,6 %) patients; (old) fractures in 3 (0,6 %) patients; bony apophyseal avulsion in 2 (0,4 %) patients and malignant tumors in 2 (0,4 %) patients. CONCLUSION: Incidental findings are common on MRI of the SI joints in children clinically suspected of JSpA, particularly at the lumbar spine and hips. They are seen even more frequently than sacroiliitis and can be relevant, as some will have clinical significance or require treatment

Elastin-like-recombinamers multilayered nanofibrous scaffolds for cardiovascular applications

Producción CientíficaCoronary angioplasty is the most widely used technique for removing atherosclerotic plaques in blood vessels. The regeneration of the damaged intima layer after this treatment is still one of the major challenges in the field of cardiovascular tissue engineering. Different polymers have been used in scaffold manufacturing in order to improve tissue regeneration. Elastin-mimetic polymers are a new class of molecules that have been synthesized and used to obtain small diameter fibers with specific morphological characteristics. Elastin-like polymers produced by recombinant techniques and called elastin-like recombinamers (ELRs) are particularly promising due to their high degree of functionalization. Generally speaking, ELRs can show more complex molecular designs and a tighter control of their sequence than other chemically synthetized polymers Rodriguez Cabello et al (2009 Polymer 50 5159–69, 2011 Nanomedicine 6 111–22). For the fabrication of small diameter fibers, different ELRs were dissolved in 2,2,2-fluoroethanol (TFE). Dynamic light scattering was used to identify the transition temperature and get a deep characterization of the transition behavior of the recombinamers. In this work, we describe the use of electrospinning technique for the manufacturing of an elastic fibrous scaffold; the obtained fibers were characterized and their cytocompatibility was tested in vitro. A thorough study of the influence of voltage, flow rate and distance was carried out in order to determine the appropriate parameters to obtain fibrous mats without beads and defects. Moreover, using a rotating mandrel, we fabricated a tubular scaffold in which ELRs containing different cell adhesion sequences (mainly REDV and RGD) were collected. The stability of the scaffold was improved by using genipin as a crosslinking agent. Genipin-ELRs crosslinked scaffolds show a good stability and fiber morphology. Human umbilical vein endothelial cells were used to assess the in vitro bioactivity of the cell adhesion domains within the backbone of the ELRs.2018-08-0

Molecular imaging of extracellular vesicles in vitro via Raman metabolic labelling

Extracellular vesicles (EVs) are biologically-derived nanovectors important for intercellular communication and trafficking. As such, EVs show great promise as disease biomarkers and therapeutic drug delivery vehicles. However, despite the rapidly growing interest in EVs, understanding of the biological mechanisms that govern their biogenesis, secretion, and uptake remains poor. Advances in this field have been hampered by both the complex biological origins of EVs, which make them difficult to isolate and identify, and a lack of suitable imaging techniques to properly study their diverse biological roles. Here, we present a new strategy for simultaneous quantitative in vitro imaging and molecular characterisation of EVs in 2D and 3D based on Raman spectroscopy and metabolic labelling. Deuterium, in the form of deuterium oxide (D2O), deuterated choline chloride (d-Chol), or deuterated D-glucose (d-Gluc), is metabolically incorporated into EVs through the growth of parent cells on medium containing one of these compounds. Isolated EVs are thus labelled with deuterium, which acts as a bio-orthogonal Raman-active tag for direct Raman identification of EVs when introduced to unlabelled cell cultures. Metabolic deuterium incorporation demonstrates no apparent adverse effects on EV secretion, marker expression, morphology, or global composition, indicating its capacity for minimally obstructive EV labelling. As such, our metabolic labelling strategy could provide integral insights into EV biocomposition and trafficking. This approach has the potential to enable a deeper understanding of many of the biological mechanisms underpinning EVs, with profound implications for the design of EVs as therapeutic delivery vectors and applications as disease biomarkers