Transplantation of immuno-isolated islets is a promising strategy to restore insulin-secreting function in patients with Type 1 diabetes. However, the clinical translation of this treatment approach remains elusive due to the loss of islet viability resulting from hypoxia at the avascular transplantation site. To address this challenge, we designed non-spherical islet-like microtissues and investigated the effect of their geometries on cellular viability. Insulin-secreting microtissues with different shapes were fabricated by assembly of monodispersed rat insulinoma beta cells on micromolded nonadhesive hydrogels. Our study quantitatively demonstrated that toroid microtissues exhibited enhanced cellular viability and metabolic activity compared to rod and spheroid microtissues with the same volume. At a similar level of cellular viability, toroid geometry facilitated efficient packing of more cells into each microtissue than rod and spheroid geometries. In addition, toroid microtissues maintained the characteristic glucose-responsive insulin secretion of rat insulinoma beta cells. Furthermore, toroid microtissues preserved their geometry and structural integrity following their microencapsulation in immuno-isolatory alginate hydrogel. Our study suggests that adopting toroid geometry in designing therapeutic microtissues potentially reduces mass loss of cellular grafts and thereby may improve the performance of transplanted islets towards a clinically viable cure for Type 1 diabetes. STATEMENT OF SIGNIFICANCE: Transplantation of therapeutic cells is a promising strategy for the treatment of a wide range of hormone or protein-deficiency diseases. However, the clinical application of this approach is hindered by the loss of cell viability and function at the avascular transplantation site. To address this challenge, we fabricated hydrogel-encapsulated islet-like microtissues with non-spheroidal geometry and optimal surface-to-volume ratio. This study demonstrated that the viability of therapeutic cells can be significantly increased solely by redesigning the microtissue configuration without requiring any additional biochemical or operational accessories. This study suggests that the adoption of toroid geometry provides a possible avenue to improve the long-term survival of transplanted therapeutic cells and expedite the translation of cell-based therapy towards clinical application.
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http://dx.doi.org/10.1016/j.actbio.2019.08.018 | DOI Listing |
Micromachines (Basel)
November 2024
Department of Mechanical and Manufacturing Engineering, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada.
This study investigates the movements of particles in an accelerated toroidal flow channel filled with water, with specific applications for a particle imaging velocimetry gyroscope (PIVG). We used computational fluid dynamics (CFD) to simulate particle behavior under different angular accelerations. These angular accelerations were 4 rad/s, 6 rad/s, and 8 rad/s for particles densities of 1100 kg/m, 1050 kg/m, and 980 kg/m.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Chemistry Research Laboratory, Department of Chemistry, Oxford OX1 3TA, U.K.
High-valent nickel species are implicated as intermediates in industrially relevant chemical transformations and in the catalytic cycles of metalloenzymes. Although a small number of tetravalent NiX complexes have been crystallographically characterized, higher nickel valence states have not been identified. Here we report a stable, crystalline NiX complex, Ni(BeCp) (; cyclopentadienyl anion (Cp)), formed by the insertion of zerovalent nickel into three Be-Be bonds.
View Article and Find Full Text PDFFront Oncol
October 2024
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United States.
Purpose: This paper discusses an advanced version of our audiovisual-assisted therapeutic ambience in radiotherapy (AVATAR) radiolucent display systems designed for pediatric radiotherapy, enabling anesthesia-free treatments, video communication, and biofeedback. The scope of the AVATAR system is expanded here in two major ways: (i) through alternative mounting systems to accommodate a broader range of radiotherapy machines (specifically to fit robotic-arm and toroidal geometry photon radiotherapy and proton radiotherapy systems) and (ii) through additional hardware to provide video-calling, optimized audio for clear communication, and combined video inputs for biofeedback, translation, and other advanced functionalities.
Methods And Materials: Because robustness requires strong parts and radio-transparency requires thin, light parts, three-dimensional printing was used to rapidly prototype hollow structures and to iteratively improve robustness.
Rev Sci Instrum
October 2024
Max-Planck-Institut für Plasmaphysik, Greifswald, Germany.
Power exhaust is one of the central challenges in magnetically confined fusion plasmas. Radiative detachment can be employed to reduce particle and heat fluxes to the divertor target, mitigating divertor damage and erosion. However, accomplishing this for a non-axisymmetric machine such as Wendelstein 7-X is a non-trivial task because of the complex role of transport and plasma-wall interaction in a three-dimensional magnetic field topology.
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