1,721,180 research outputs found

    Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

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    Tissue 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

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    In 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

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    In 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

    Hypo-and hyperthermia effects on macroscopic fluid transport in tumors

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    Combining the effects of transvascular and interstitial fluid movement with the structural mechanics of a tissue is necessary to properly analyze processes such as nutrient transport in a tumor cell. Furthermore, externally induced heat loads can play a role: for example, cryoablation can be performed by means of hypothermia and hyperthermia can be induced in order to treat some kinds of tumors such as liver tumor. Recently, the study of the effects of hypo-and hyperthermia on fluid flow and mass transport in biological systems by considering the fluid–structure interaction has gained researchers’ attention. In this paper, fluid flow in a tumor mass is analyzed at the macroscopic scale by considering the effects of both solid tissue deformation and temperature via hypo-and hyperthermia. Governing equations are averaged over a representative elementary volume of the living tissue, and written by means of the thermo-poroelasticity theory. Darcy’s law is used to describe fluid flow through the interstitial space, while transvascular transport is described with a generalized Starling’s law. The effects of hypo-and hyperthermia on the living tissue are included with a source term in the tissue momentum equation that considers thermal expansion. This term can be either negative or positive, i.e., hypo-or hyperthermia is herein considered. Governing equations with the appropriate boundary conditions are solved with the finite-element commercial code COMSOL Multiphysics in the steady-state regime. The numerical model is validated with analytical results from previously published results for an isothermal case. Results are presented in terms of pressure, velocity, and temperature fields for various thermal loads and the effects of hypo-and hyperthermia on various physical parameters are analyzed
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