TEDD Competence Centre Report 2019

Copyright ©Swiss Chemical Society: CHIMIA, Volume 74, Number 5, 2020, pp. 426-428, 10.2533/chimia.2020.426TEDD (Tissue Engineering for Drug Development and Substance Testing) is an education, R&D and networking platform promoting the application of 3D organotypic technologies, with the core goal of replacing animal experimentation for therapy development. Based in Switzerland, TEDD is one of its kind in Europe focused on 3D for 3Rs. The community is composed of international members from academia, clinics, industry and non-profits. Training of members is achieved through regular events at the national and international level, including workshops, symposia, company visits, scientific reviews and by providing the platform to generate research consortia, projects and grant applications

Cross-industrial applications of organotypic models

Recent advances in microphysiological systems (MPS) promise a global paradigm shift in drug development, diagnostics, disease prevention, and therapy. The expectation is that these systems will model healthy and various diseased stages and disease progression to predict toxicity, immunogenicity, ADME profiles, and treatment efficacies. MPS will provide unprecedented human-like physiological properties of in vitro models, enabling their routine application in the pharma industry and thus reducing drug development costs by lowering the attrition rate of compounds. We showcased MPS application diversity across different industries during the TEDD Annual Meeting on 14th October 2021 in Wädenswil, Switzerland. The goal was to promote cross-sectoral collaboration of academia and industry to further pave the way for developing next-generation MPS based on 3D cell culture, organoid, and organ-on-chip technology and their widespread exploitation. To enable visionary projects and radical innovations, we covered multidisciplinary fields and connected different industry sectors, like pharma, medtech, biotech, cosmetics, diagnostics, fragrances, and food, with each other

TEDD annual meeting with 3D bioprinting workshop

Bioprinting is the technology of choice for realizing functional tissues such as vascular system, muscle, cartilage and bone. In the future, bioprinting will influence the way we engineer tissues and bring it to a new level of physiological relevance. That was the topic of the 2017 TEDD Annual Meeting at ZHAW Wädenswil on 8-9 November. In an exciting workshop, the two companies regenHU Ltd. and CELLINK gave us an insight into highly topical applications and collaborations in this domain

Properties of additive-manufactured open porous titanium structures for patient-specific load-bearing implants

Additive manufacturing has been well established in many sectors, including the medical industry. For load-bearing bone implants, titanium and its alloys, such as Ti6Al4V, are widely used due to their high strength to weight ratio and osseointegrative properties. However, bone resorption and loosening of implants is related to the significantly higher stiffness of dense Ti6Al4V, leading to stress shielding. With the aging of population, there is an increasing need for orthopedic implants with a high success rate and a long implant life span. Besides that the treatment of non-healing segmental bone defects, where the self repairing properties of bone tissue are not sufficient, is still a challenge. In both fields of application, patient-specific titanium implants combined with functionally graded porosity designed according to locally expected loads unlock new possibilities. Many studies underline the huge potential of the new design freedom to generate open porous structures and more personalized implants with enhanced mechanical properties that also integrate well with surrounding tissues. Integration of functionally graded open porosity into implants allows for the implant to more closely mimic the mechanical properties of human bone and its internal architecture. The results of this work represent the basis for developing complex porous titanium structures with various pore sizes and shapes to tailor structural mechanical properties and biological responses. Therefore, 3D porous structures with various pore sizes and shapes were designed and manufactured in Ti6Al4V using laser powder bed fusion (PBF-LB/M). Based on these structures, the correlation of pore size and shape with cell ingrowth, morphology, metabolic activity, and early markers for bone formation (ALP activity) was investigated in static cell cultures using the osteosarcoma cell line Saos-2. Mechanical properties, such as stiffness and compression strength, were investigated with compression testing. The present study concludes that cell morphology, metabolic activity, and ALP activity are widely independent of pore shape and size within the tested range of 400–700 µm pore size. Furthermore, the mechanical properties of the evaluated structures were in the range of cortical and trabecular bone. This opens the possibility to design mechanical properties with gradient porosity without decisively affecting biological responses

1-[2-(2,4-Dichloro­benz­yloxy)-2-(furan-2-yl)eth­yl]-1H-benzotriazole

In the title compound, C19H15Cl2N3O2, the benzotriazole ring system is approximately planar [maximum deviation = 0.018 (2) Å] and its mean plane is oriented at dihedral angles of 30.70 (5) and 87.38 (4)°, respectively, to the furan and benzene rings while the dihedral angle between furan and benzene rings is 74.46 (6)°. In the crystal, weak C—H⋯N hydrogen bonds link the mol­ecules into chains along the b axis. π–π stacking inter­actions between the parallel dichloro­benzene rings of adjacent mol­ecules [centroid–centroid distance = 3.6847 (9) Å] and weak C—H⋯π inter­actions are also observed

Does the partial molar volume of a solute reflect the free energy of hydrophobic solvation?

Halogenated heterocyclic ligands are widely used as the potent and frequently selective inhibitors of protein kinases. However, the exact contribution of the hydrophobic solvation of a free ligand is rarely accounted for the balance of interactions contributing to the free energy of ligand binding. Herein, we propose a new experimental method based on volumetric data to estimate the hydrophobicity of a ligand. We have tested this approach for a series of ten variously halogenated benzotriazoles, the binding affinity of which to the target protein kinase CK2 was assessed with the use of thermal shift assay. According to the hierarchical clustering procedure, the excess volume, defined as the difference between the experimentally determined partial molar volume and the calculated in silico molecular volume, was found to be distant from any commonly used hydrophobicity descriptors of the ligand. The excess volume, however, properly predicts solute binding affinity. On the way, we have proved that the binding of halogenated benzotriazoles to the protein kinase CK2 is driven mostly by hydrophobic interaction

Multiplier effects in agriculture

Przedstawiono wnioski wypływające z przeglądu literatury dotyczącej badań nad efektami mnożnikowymi występującymi w rolnictwie. Wyjaśniono, czym jest mnożnik, następnie omówiono efekty mnożnikowe występujące w sektorze rolniczym. Na podstawie literatury przedmiotu zaprezentowano wyniki badań analizujących efekty mnożnikowe w rolnictwie. Można stwierdzić, że rozwój rolnictwa przyczynia się do tworzenia efektów mnożnikowych nie tylko w rolnictwie, ale również w innych sektorach gospodarki.The paper presents the conclusions stemming from the literature review concerning studies on multiplier effects present in the agriculture. Firstly, the concept of a multiplier is presented. Then, multiplier effects in the agriculture are described. Finally, based on a literature review, results of studies on multiplier effects in the agriculture are discussed. Following the conducted literature review study it can be concluded that the development of agriculture creates multiplier effects not only in the agriculture, but also in the other sectors of the economy

Zespół Wolfa–Hirschhorna – opis przypadku

Wolf–Hirschhorn syndrome is a severe genetic condition that affects many systems of the human body. The genetic mechanism is based on the deletion of the distal portion of the short arm of chromosome 4 (4p). Individuals affected by the syndrome have a special phenotype: wide bridge of the nose, widely spaced eyes, micrognathia, microcephaly, growth retardation, cryptorchidism, heart defects, hearing loss and severe intellectual disability. The patient from our case report was hospitalised at the Lviv City Children’s Hospital at the age of six hours in a severe condition, with distinctive features of a genetic syndrome, which was connected with intraventricular haemorrhage. At the age of three months, he showed delayed physical and neurocognitive development and a characteristic appearance, which led to a specialist consultation to diagnose the genetic disease. This time, on the basis of clinical, laboratory and instrumental findings, the boy was diagnosed with Wolf–Hirschhorn syndrome.Zespół Wolfa–Hirschhorna jest ciężką chorobą genetyczną objawiającą się szeregiem wad wrodzonych dotykających różnych układów ludzkiego organizmu. Mechanizm genetyczny tego zespołu polega na delecji dystalnej części krótkiego ramienia chromosomu 4 (4p). Osoby dotknięte tym schorzeniem mają charakterystyczny fenotyp, na który składają się m.in. szeroka podstawa nosa, szeroko rozstawione oczy, mikrognacja, mikrocefalia, upośledzenie wzrostu, wnętrostwo, wady serca, ubytki słuchu oraz ciężkie upośledzenie intelektualne. Przedstawiony w pracy pacjent był hospitalizowany w Miejskim Szpitalu Dziecięcym we Lwowie w 6. godzinie życia w stanie ciężkim, z wyraźnymi cechami zespołu zaburzeń genetycznych oraz krwawieniem dokomorowym. W wieku 3 miesięcy, ze względu na wyraźnie opóźniony rozwój motoryczny oraz neuropoznawczy, a także charakterystyczne cechy fizjonomiczne, pacjenta skierowano do konsultacji genetycznej w celu ustalenia rozpoznania. W oparciu o wyniki badań fizykalnych, laboratoryjnych i genetycznych stwierdzono u niego zespół Wolfa–Hirschhorna