129 research outputs found
Microfluidic device and relative method for the generation and/or culture and/or maturation of three- dimensional cell and/or tissue constructs
No full textMicrofluidic device and relative method for the generation and/or culture and/or maturation of three-dimensional cells and/or tissue constructs
No full textProjective manifolds containing a large linear subspace with nef normal bundle
No full textWe classify smooth complex projective varieties of dimension in containing a linear subspace of dimension whose normal bundle is numerically effective
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
Bone Marrow on chip: unravelling mesenchymal-hematopoietic crosstalk
No full textBone marrow (BM) niche is a complex environment made of a stromal and a hematopoietic cellular components. MSCs (mesenchymal stem cells) have a pivotal role in HSCs (hematopoietic stem cells) regulation since they help in preserving their stemness and the balance between self-renewal and differentiation. Such crosstalk is also involved in pathological events: as an example BMSCs can sense peripheral tumour and, by the secretion of IL1β, alter HSC transcription factors activation and guide related differentiation.Organs on chip (OoC) technology can be considered an effective strategy to overcome 2D culture and animal models limitations in modelling such BM niche, by reproducing a highly controlled microenvironment that preserves niche properties in terms of HSCs stemness and differentiation potential. The aim of this study was the development of a functional BM on chip to study the interaction of MSCs on HSCs in a 3D in-vitro microenvironment and at the same time create a model of endosteum niche including multipotent and differentiated MS
Learn, simplify and implement: developmental re-engineering strategies for cartilage repair
No full textThe limited self-healing capacity of cartilage in adult individuals, and its tendency to deteriorate once structurally damaged, makes the search for therapeutic strategies following cartilage-related traumas relevant and urgent. To date, autologous cell-based therapies represent the most advanced treatments, but their clinical success is still hampered by the long-term tendency to form fibrous as opposed to hyaline cartilage tissue. Would the efficiency and robustness of therapies be enhanced if cartilage regeneration approaches were based on the attempt to recapitulate processes occurring during cartilage development ("developmental engineering")? And from this perspective, shouldn't cartilage repair strategies be inspired by development, but adapted to be effective in a context (an injured joint in an adult individual) that is different from the embryo ("developmental re-engineering")? Here, starting from mesenchymal stem/stromal cells (MSCs) as an adult cell source possibly resembling features of the embryonic mesenchyme, we propose a developmental re-engineering roadmap based on the following three steps: (i) learn from embryonic cartilage development which are the key pathways involved in MSC differentiation towards stable cartilage, (ii) simplify the complex developmental events by approximation to essential molecular pathways, possibly by using in vitro high-throughput models and, finally, (iii) implement the outcomes at the site of the injury by establishing an appropriate interface between the delivered signals and the recipient environment (e.g., by controlling inflammation and angiogenesis). The proposed re-design of developmental machinery by establishing artificial developmental events may offer a chance for regeneration to those tissues, like cartilage, with limited capacity to recover from injuries
Development of a 3D human in vitro model of idiopathic pulmonary fibrosis in a Lung-on-a-Chip device
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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
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