Roofed grooves: Rapid layer engineering of perfusion channels in collagen tissue models

Surface patterning (micro-moulding) of dense, biomimetic collagen is a simple tool to produce complex tissues using layer-by-layer assembly. The aim here was to channelise three-dimensional constructs for improved perfusion. Firstly, collagen fibril accumulation was measured by comparative image analysis to understand the mechanisms of structure formation in plastically compressed collagen during µ-moulding. This showed that shape (circular or rectangular) and dimensions of the template affected collagen distribution around moulded grooves and consequently their stability. In the second part, this was used for effective fabrication of multi-layered plastically compressed collagen constructs with internal channels by roofing the grooves with a second layer. Using rectangular templates of 25/50/100 µm widths and 75 µm depth, grooves were µ-moulded into the fluid-leaving surface of collagen layers with predictable width/depth fidelities. These grooves were then roofed by addition of a second plastically compressed collagen layer on top to produce µ-channels. Resulting µ-channels retained their dimensions and were stable over time in culture with fibroblasts and could be cell seeded with a lining layer by simple transfer of epithelial cells. The results of this study provide a valuable platform for rapid fabrication of complex collagen-based tissues in particular for provision of perfusing microchannels through the bulk material for improved core nutrient supply

Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe

Effects and safety profile of betahistine in patients in the Russian contingent of OSVaLD, an open-label observational study in vestibular vertigo

Svetlana Vyacheslavovna Morozova,1 Natalia Stepanovna Alekseeva,2 Sergey Vasilyevich Lilenko,3 Eduard Ivanovich Matsnev,4 Oleg Anatol'evich Melnikov51Department of Ear, Nose, and Throat, State Budgetary Educational Institution of Higher Professional Training, IM Sechenov First Moscow State Medical University of the Ministry of Healthcare and Social Development of the Russian Federation, Moscow, 2Federal State Budgetary Institution, Scientific Neurology Center of the Russian Academy of Medical Sciences, Moscow, 3St Petersburg Research Institute of Ear, Throat, Nose and Speech, St Petersburg, 4Department of Physiology and Pathology of Auditory and Vestibular Systems, Federal Scientific Center (FSC), Institute for Biomedical Problems, Russian Academy of Sciences (RAS), Moscow, 5ANO Guta Clinic, Moscow, Russian Federation Background: We report here data from the >200 patients recruited in Russia to take part in OSVaLD, a 12-week, open-label, post-marketing surveillance study of the response to betahistine 48 mg/day in vertigo of peripheral vestibular origin carried out in a total of 13 countries.Methods: The primary efficacy endpoint was change in the Dizziness Handicap Inventory (DHI; 100-point scale). Changes in Hospital Anxiety and Depression Scale (HADS) and Medical Outcomes Study Short-Form 36, version 2 (SF-36v2®) scores were a priori secondary Outcomes.Results: Total DHI score improved by 43 points during betahistine treatment. This aggregate improvement was equally distributed across the three domains of the DHI (physical, emotional, and functional; P<0.0001 for main and subscore changes from baseline). Statistically significant improvements versus baseline were also observed in mean HADS scores for anxiety and depression (both P<0.0001), and in the Physical Component Summary and Mental Component Summary scores of the SF-36v2 (both P<0.0001 versus baseline). Only one suspected adverse drug reaction was recorded in the Russian safety population (n=204), indicating that betahistine was well tolerated in those patients.Conclusion: Betahistine 48 mg/day was associated with clear improvements in well-configured and widely validated measures of health-related quality of life and an encouraging tolerability profile in patients in Russia who took part in OSVaLD.Keywords: betahistine, vertigo, dizziness, anxiety, depression, quality of life, Russi