195 research outputs found
Electromechanical Stimulation of 3D Cardiac Microtissues in a Heart-on-Chip Model
No full textModeling human cardiac tissues in vitro is essential to elucidate the biological mechanisms related to the heart physiopathology, possibly paving the way for new treatments. Organs-on-chips have emerged as innovative tools able to recreate tissue-specific microenvironments, guiding the development of miniaturized models and offering the opportunity to directly analyze functional readouts. Here we describe the fabrication and operational procedures for the development of a heart-on-chip model, reproducing cardiac biomimetic microenvironment. The device provides 3D cardiac microtissue with a synchronized electromechanical stimulation to support the tissue development. We additionally describe procedures for characterizing tissue evolution and functionality through immunofluorescence, real time qPCR, calcium imaging and microtissue contractility investigations
Mechanical Induction of Osteoarthritis Traits in a Cartilage-on-a-Chip Model
No full textThe present lack of effective therapies for osteoarthritis, the most diffused musculoskeletal disease, correlates with the absence of representative in vitro disease models. Microfabrication techniques and soft lithography allow the development of organs and tissues on chip with increased mimicry of human pathophysiology. Exploitation of polydimethylsiloxane elasticity, furthermore, permits to incorporate finely controlled mechanical actuators which are of the utmost importance in a faithful representation of the intrinsically active environment of musculoskeletal districts, to increase our comprehension of the disease onset and to successfully predict the response to pharmacological therapies. Here, we portray the fabrication and operational processes for the development of a cartilage-on-a-chip model. Additionally, we describe the methodologies to induce a phenotype reminiscent of osteoarthritis solely through hyperphysiological cyclic compression. The techniques to assess achievement of such features through immunofluorescence and gene expression are also detailed
Photo and Soft Lithography for Organ-on-Chip Applications
No full textOrgans-on-Chip devices are generally fabricated by means of photo- and soft lithographic techniques. Photolithography is a process that involves the transfer of a pattern onto a substrate by a selective exposure to light. In particular, in this chapter two different photolithography methods will be described: liquid and dry photolithography. In liquid photolithography, a silicon wafer is spin-coated with liquid photoresist and exposed to UV light in order to be patterned. In dry photolithography, the silicon wafer is laminated with resist dry film before being patterned through UV light. In both cases, the UV light can be collimated on top of the wafer either through photomasks or by direct laser exposure. The obtained patterned wafer is then used as a mold for the soft lithographic process (i.e., replica molding) to produce polymer-based microdevices
Organ-on-Chips for Studying Tissue Barriers: Standard Techniques and a Novel Method for Including Porous Membranes Within Microfluidic Devices
No full textA relevant number of organ-on-chips is aimed at modeling epithelial/endothelial interfaces between tissue compartments. These barriers help tissue function either by protecting (e.g., endothelial blood–brain barrier) or by orchestrating relevant molecular exchanges (e.g., lung alveolar interface) in human organs. Models of these biological systems are aimed at characterizing the transport of molecules, drugs or drug carriers through these specific barriers. Multilayer microdevices are particularly appealing to this goal and techniques for embedding porous membranes within organ-on-chips are therefore at the basis of the development and use of such systems. Here, we discuss and provide procedures for embedding porous membranes within multilayer organ-on-chips. We present standard techniques involving both custom-made polydimethylsiloxane (PDMS) membranes and commercially available plastic membranes. In addition, we present a novel method for fabricating and bonding PDMS porous membranes by using a cost-effective epoxy resin in place of microfabricated silicon wafers as master molds
Liver–Heart on chip models for drug safety
No full textCurrent pre-clinical models to evaluate drug safety during the drug development process (DDP) mainly rely on traditional two-dimensional cell cultures, considered too simplistic and often ineffective, or animal experimentations, which are costly, time-consuming, and not truly representative of human responses. Their clinical translation thus remains limited, eventually causing attrition and leading to high rates of failure during clinical trials. These drawbacks can be overcome by the recently developed Organs-on-Chip (OoC) technology. OoC are sophisticated in vitro systems capable of recapitulating pivotal architecture and functionalities of human organs. OoC are receiving increasing attention from the stakeholders of the DDP, particularly concerning drug screening and safety applications. When a drug is administered in the human body, it is metabolized by the liver and the resulting compound may cause unpredicted toxicity on off-target organs such as the heart. In this sense, several liver and heart models have been widely adopted to assess the toxicity of new or recalled drugs. Recent advances in OoC technology are making available platforms encompassing multiple organs fluidically connected to efficiently assess and predict the systemic effects of compounds. Such Multi-Organs-on-Chip (MOoC) platforms represent a disruptive solution to study drug-related effects, which results particularly useful to predict liver metabolism on off-target organs to ultimately improve drug safety testing in the pre-clinical phases of the DDP. In this review, we focus on recently developed liver and heart on chip systems for drug toxicity testing. In addition, MOoC platforms encompassing connected liver and heart tissues have been further reviewed and discussed
Microfluidic device and relative method for the generation and/or culture and/or maturation of three- dimensional cell and/or tissue constructs
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Microfluidic device and relative method for the generation and/or culture and/or maturation of three-dimensional cells and/or tissue constructs
No full textConstellation of early childhood, Gugu’s firmament. A portrait of Augusta Rasponi del Sale (Ravenna 1864-1942), author of picture book
No full textAugusta Rasponi del Sale (1864 – 1942) aka Gugù wrote and illustrated children’s picture books published in England, France, Italy; she dedicated her work to the representation of early childhood. She used to portray herself as a duck, or goose and she devoted her life to neglected children. She looked at childhood from a unique point of view – her work as an author focused on representing all children, also infants of the age of one, two and three months, dedicating realistic portraits and poetic verses to them. What emerges from her work is a modern way to conceive children’s books and early childhood life conditions and rights. She created a cultural portrait of childhood of her time – representing not only childhood but also early childhood. This article focuses on her work, in order to rediscover the value of a great, forgotten children’s literature author still capable to amaze scholars and educators
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