1,720,999 research outputs found
In vitro three-dimensional models in cancer research: A review
No full textThree-dimensional (3D) cell cultures have recently garnered great attention because they promote levels of cells differentiation and tissue organisation not possible in conventional two-dimensional (2D) culture systems. Cancer development is a complex process regulated by interactions between epithelial cells, activated stromal cells, and soluble and insoluble components of the extracellular matrix (ECM). As a consequence, in the field of cancer biology a 3D tumour model that accurately recreates the in vivo tumour phenotype would be a valuable tool for studying tumour biology and would allow better pre-clinical evaluation of anticancer drug candidates. Here, we review the 3D tumour models currently available and the more advanced techniques from the tissue-engineering field used to create a more clinically accurate ex vivo tumour model. Moreover, we highlight the drastic differences in drug responses between 3D and 2D models and give a glance to the emerging multi-organ microdevices that can mimic in vivo tissue-tissue interactions
Carditello 4.0
No full textLa soluzione che si intende sviluppare ed industrializzare afferisce alla realizzazione di una piattaforma integrata in grado di supportare i processi di monitoraggio degli inquinanti e la loro caratterizzazione nel contesto antropico ed ambientale di riferimento. In particolare si intende mettere a punto sensori in grado di valutare la quantità di diossina presente negli individui correlando tali informazioni con le bio- banche e le informazioni del contesto antropico ed ambientale di riferimento. Il progetto punta a realizzare sensoristica a basso costo che consentono una capillare diffusione sul territorio e una loro correlazione con il complesso delle informazioni acquisibili sul territorio e disponibili nel complesso delle bio-banche già presenti ed in allestimento in Regione Campania
Engineering Cell Instructive Microenvironments for In Vitro Replication of Functional Barrier Organs
No full textMulticellular organisms exhibit synergistic effects among their components, giving rise to emergent properties crucial for their genesis and overall functionality and survival. Morphogenesis involves and relies upon intricate and biunivocal interactions among cells and their environment, that is, the extracellular matrix (ECM). Cells secrete their own ECM, which in turn, regulates their morphogenetic program by controlling time and space presentation of matricellular signals. The ECM, once considered passive, is now recognized as an informative space where both biochemical and biophysical signals are tightly orchestrated. Replicating this sophisticated and highly interconnected informative media in a synthetic scaffold for tissue engineering is unattainable with current technology and this limits the capability to engineer functional human organs in vitro and in vivo. This review explores current limitations to in vitro organ morphogenesis, emphasizing the interplay of gene regulatory networks, mechanical factors, and tissue microenvironment cues. In vitro efforts to replicate biological processes for barrier organs such as the lung and intestine, are examined. The importance of maintaining cells within their native microenvironmental context is highlighted to accurately replicate organ-specific properties. The review underscores the necessity for microphysiological systems that faithfully reproduce cell-native interactions, for advancing the understanding of developmental disorders and disease progression
In vitro strategies for mimicking dynamic cell–ECM reciprocity in 3D culture models
No full textThe extracellular microenvironment regulates cell decisions through the accurate presentation at the cell surface of a complex array of biochemical and biophysical signals that are mediated by the structure and composition of the extracellular matrix (ECM). On the one hand, the cells actively remodel the ECM, which on the other hand affects cell functions. This cell–ECM dynamic reciprocity is central in regulating and controlling morphogenetic and histogenetic processes. Misregulation within the extracellular space can cause aberrant bidirectional interactions between cells and ECM, resulting in dysfunctional tissues and pathological states. Therefore, tissue engineering approaches, aiming at reproducing organs and tissues in vitro, should realistically recapitulate the native cell–microenvironment crosstalk that is central for the correct functionality of tissue-engineered constructs. In this review, we will describe the most updated bioengineering approaches to recapitulate the native cell microenvironment and reproduce functional tissues and organs in vitro. We have highlighted the limitations of the use of exogenous scaffolds in recapitulating the regulatory/instructive and signal repository role of the native cell microenvironment. By contrast, strategies to reproduce human tissues and organs by inducing cells to synthetize their own ECM acting as a provisional scaffold to control and guide further tissue development and maturation hold the potential to allow the engineering of fully functional histologically competent three-dimensional (3D) tissues
Engineered cardiac micromodules for the in vitro fabrication of 3D endogenous macro-tissues
No full textBioprinting of human dermal microtissues precursors as building blocks for endogenous in vitro connective tissue manufacturing
No full textThe advent of 3D bioprinting technologies in tissue engineering has unlocked the potential to fabricate in vitro tissue models, overcoming the constraints associated with the shape limitations of preformed scaffolds. However, achieving an accurate mimicry of complex tissue microenvironments, encompassing cellular and biochemical components, and orchestrating their supramolecular assembly to form hierarchical structures while maintaining control over tissue formation, is crucial for gaining deeper insights into tissue repair and regeneration. Building upon our expertise in developing competent three-dimensional tissue equivalents (e.g. skin, gut, cervix), we established a two-step bottom-up approach involving the dynamic assembly of microtissue precursors (μTPs) to generate macroscopic functional tissue composed of cell-secreted extracellular matrix (ECM). To enhance precision and scalability, we integrated extrusion-based bioprinting technology into our established paradigm to automate, control and guide the coherent assembly of μTPs into predefined shapes. Compared to cell-aggregated bioink, our μTPs represent a functional unit where cells are embedded in their specific ECM. μTPs were derived from human dermal fibroblasts dynamically seeded onto gelatin-based microbeads. After 9 days, μTPs were suspended (50% v/v) in Pluronic-F127 (30% w/v) (μTP:P30), and the obtained formulation was loaded as bioink into the syringe of the Dr.INVIVO-4D6 extrusion based bioprinter. μTP:P30 bioink showed shear-thinning behavior and temperature-dependent viscosity (gel at T > 30 °C), ensuring μTPs homogenous dispersion within the gel and optimal printability. The bioprinting involved extruding several geometries (line, circle, and square) into Pluronic-F127 (40% w/v) (P40) support bath, leveraging its shear-recovery property. P40 effectively held the bioink throughout and after the bioprinting procedure, until μTPs fused into a continuous connective tissue. μTPs fusion dynamics was studied over 8 days of culture, while the resulting endogenous construct underwent 28 days culture. Histological, immunofluorescence analysis, and second harmonic generation reconstruction revealed an increase in endogenous collagen and fibronectin production within the bioprinted construct, closely resembling the composition of the native connective tissues
Building a tissue in vitro from the bottom up: implications in regenerative medicine
No full textTissue engineering aims at creating biological tissues to improve or restore the function of diseased or damaged tissues. To enhance the performance of engineered tissues, it is required to recapitulate in vitro not only the composition but also the structural organization of native tissues. To this end, tissue engineering techniques are beginning to focus on generating micron-sized tissue modules having specific microarchitectural features that can be used alone as living filler in the damaged areas or serve as building blocks to engineer large biological tissues by a bottom-up approach. This work discusses the shortcomings related to traditional ???top-down??? strategies and the promises of emerging ??????bottom-up??? approaches in creating engineered biological tissues. We first present an overview of the current tissue-building techniques and their applications, with an analysis of the potentiality and shortcomings of different approaches. We then propose and discuss a novel method for the biofabrication of connective-like micro tissues and how this technique can be translated to cardiac muscle fabrication
In vitro organotypic systems to model tumor microenvironment in human papillomavirus (HPV)-related cancers
No full textDespite the well-known role of chronic human papillomavirus (HPV) infections in causing tumors (i.e., all cervical cancers and other human malignancies from the mucosal squamous epithelia, including anogenital and oropharyngeal cavity), its persistence is not sufficient for cancer development. Other co-factors contribute to the carcinogenesis process. Recently, the critical role of the underlying stroma during the HPV life cycle and HPV-induced disease have been investigated. The tumor stroma is a key component of the tumor microenvironment (TME), which is a specialized entity. The TME is dynamic, interactive, and constantly changing—able to trigger, support, and drive tumor initiation, progression, and metastasis. In previous years, in vitro organotypic raft cultures and in vivo genetically engineered mouse models have provided researchers with important information on the interactions between HPVs and the epithelium. Further development for an in-depth understanding of the interaction between HPV-infected tissue and the surrounding microenvironment is strongly required. In this review, we critically describe the HPV-related cancers modeled in vitro from the simplified ‘raft culture’ to complex three-dimensional (3D) organotypic models, focusing on HPV-associated cervical cancer disease platforms. In addition, we review the latest knowledge in the field of in vitro culture systems of HPV-associated malignancies of other mucosal squamous epithelia (anogenital and oropharynx), as well as rare cutaneous non-melanoma associated cancer
An engineered breast cancer model on chip for personalized and multiple drug therapy
No full textBreast cancer is one of the most common tumors worldwide featured by heterogeneity. The expression of hormone receptors marks different breast cancer subtypes. Each type is pharmacologically treated by using molecules targeting hormone receptors, but this frequently drives chemoresistance. For this reason, the possibility to replicate this hostile human pathology in vitro represents an urgent need to understand the biological basis behind heterogeneity and chemoresistance and explore the efficiency of pharmacological treatments
Time and space evolution of transport properties in agarose-chondrocyte constructs
No full textDuring the development of de novo synthesized cartilage tissue engineered constructs, transport and biophysical properties are expected to change in time and space. Monitoring and control of the evolution of these parameters are of crucial importance to process biohybrid constructs in vitro. The aim of this work was to measure fluid and macromolecular transport and evolution of mechanical properties of tissue-engineered cartilage constructs as a function of culture time and extracellular matrix (ECM) production. It was found, in agreement with other literature reports, that mechanical and fluid transport properties of the constructs correlated well with time of culture and glycosaminoglycan (GAG) content. Further, diffusion coefficients of 2 probes, dextran (500 kDa) and bovine serum albumin (BSA), correlated well with GAG production. Diffusion coefficients (D) were measured with high spatial and temporal resolution by fluorescent recovery after photobleaching (FRAP). Diffusivity steadily decreases with time while it does not vary through the thickness of the specimen. On the basis of these results, an empirical relationship between diffusion coefficient and GAG content was proposed for the 2 probes analyzed. The results of this study provide useful information to optimize and control the tissue culture process in vitro
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