1,721,135 research outputs found
Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules
No full textTissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among these strategies, emerging computer aided design and manufacturing processes, such as modular tissue unit patterning, promise to provide unprecedented control over the generation of biologically and biomechanically competent tissue analogues. This review discusses recent studies and highlights the role of scaffold microstructural properties and their drug release capability in cell fate control and tissue morphogenesis. Furthermore, the work highlights recent advances in the bottom-up fabrication of porous scaffolds and hybrid constructs through the computer-aided assembly of cell-free and/or cell-laden micro-modules. The advantages, current limitations, and future challenges of these strategies are described and discussed
A thermoporoelastic model for fluid transport in tumour tissues
No full textIn this paper, the effect of coupled thermal dilation and stress on interstitial fluid transport in tumour tissues is evaluated. The tumour is modelled as a spherical deformable poroelastic medium embedded with interstitial fluid, while the transvascular fluid flow is modelled as a uniform distribution of fluid sink and source points. A hyperbolic-decay radial function is used to model the heat source generation along with a rapid decay of tumour blood flow. Governing equations for displacement, fluid flow and temperature are first scaled and then solved with a finite-element scheme. Results are compared with analytical solutions from the literature, while results are presented for different scaling parameters to analyse the various physical phenomena. Results show that temperature affects pressure and velocity fields through the deformable medium. Finally, simulations are performed by assuming that the heat source is periodic, in order to assess the extent to which this condition affects the velocity field. It is reported that in some cases, especially for periodic heating, the combination of thermoelastic and poroelastic deformation led to no monotonic pressure distribution, which can be interesting for applications such as macromolecule drug delivery, in which the advective contribution is very important owing to the low diffusivity
A high throughput approach based on dynamic high pressure for the encapsulation of active compounds in exosomes for precision medicine
No full textIn recent decades, endogenous nanocarrier-exosomes have received considerable scientific interest as drug delivery systems. The unique proteo-lipid architecture allows the crossing of various natural barriers and protects exosomes cargo from degradation in the bloodstream. However, the presence of this bilayer membrane as well as their endogenous content make loading of exogenous molecules challenging. In the present work, we will investigate how to promote the manipulation of vesicles curvature by a high-pressure microfluidic system as a ground-breaking method for exosomes encapsulation. Exosomes isolated from Uppsala 87 Malignant Glioma (U87MG) cell culture media were characterized before and after the treatment with high-pressure homogenization. Once their structural and biological stability were validated, we applied this novel method for the encapsulation in the lipidic exosomal bilayer of the chemotherapeutic Irinotecan HCl Trihydrate-CPT 11. Finally, we performed in vitro preliminary test to validate the nanobiointeraction of exosomes, uptake mechanisms, and cytotoxic effect in cell culture model
A novel microfluidic-based approach to study protein stability behavior in highly concentrated and viscous (HCV) systems
No full textThe protein stability in protein-based therapeutic injectables (typically highly concentrated and viscous (HCV) solutions) is essential, as its lack determines mild to severe immune response in patients. Commonly, protein stabilization is attempted by adding stabilizers to the biomolecule solutions that are consequently studied by being exposed to physico-chemical solicitations to induce protein destabilization. Standard protocols to study protein HCV solutions rely on batch approaches, that exhibit poor controllability and are time- and reagent-consuming. Because of this and due to the rheological complexity of these fluids, there is still poor scientific knowledge about the correlation between protein stability in HCV systems and destabilization factors. Also, just a little is known about the role and the interaction of stabilizing agents with biomolecule in solution. Here a novel miniaturized approach based on microfluidics to study protein behavior in HCV systems is proposed. While requiring minimum solution volumes to be processed, the automated microfluidic platform can stimulate HCV protein solutions, offering fine controllability of stimulating environment in a wide viscosity range and in a broad spectrum of thermal and mechanical stimuli. As proof of concept, some results from light scattering-based analysis comparing stimulated and unstimulated HCV BSA solutions are presented
Mesenchymal Stem Cell Response to Micropatterns and Dynamic Topographies
No full textThe native extracellular matrix is a dynamic environment, but it is not clear how cells react to time changing signals. To investigate this, we exploited light responsive azobenzene based platforms, able to display spatiotemporal changes of topographic signals. Mesenchymal stem cells were cultivated on either rectangular or circular adhesive islets in order to promote either a high or low contractile phenotype. Submicron scale topography was switched on at selected time points to interfere with adhesion and cytoskeleton assembly. Cells responded to the dynamic changes by altering their mechanical properties, lamins expression and YAP nuclear import. Changes at receptor or cytoskeleton level are observed a relatively small timeframes, whereas Lamins and YAP nuclear accumulation required longer times. Our data could be useful to develop culturing systems able to challenge stem cells with specific programmes of mechanical/topographical signals thus understanding how cells integrate those in time
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
Prediction of injectables' stability leveraging inline analysis and machine learning
No full textAggregation and modification of the structure of biologics (i.e., proteins, mAbs, etc.) can significantly affect the quality of the final biopharmaceutical product, especially because of the increased risk of immunogenicity and the decreased specificity. The excipients in the final formulation are intended to mitigate destabilizing effects (e.g., aggregation, structural/conformational modifications, etc.). Here, we describe a novel high-throughput screening approach based on a microfluidic inline analytical platform and machine learning methods, to select the best formula composition in terms of type and concentration of excipients needed to reduce the aforementioned destabilizing effects. We show how to collect stability-related information in a fast and reliable way, with minimum material amount (i.e., few hundreds of microliters), and how to properly structure the dataset for subsequent machine learning-based processing. This approach is taught to dramatically reduce the number of experiments needed for later fine characterization of injectables' stability
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