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. 2021 Oct 6;12:5846. doi: 10.1038/s41467-021-26126-w

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a Annotated schematic of the central section of a hypothetical SONIC spiral device, including the SONIC scaffold (blue) arranged in an Archimedean spiral (with the distance between turns fixed at 500 μm) and hydrogel-encapsulated human islets (red). A thickness of 1.2 mm ensures a maximum distance of insulin diffusion of 600 μm; a diameter of 4.75 mm was used for simulations, representing the central section of a device scaled radially to achieve a sufficient encapsulated islet payload. b Schematics showing the SONIC spiral device and scaffold-free control device encapsulating 4%, 6%, 8%, and 10% human islets (volume of islets per volume of device), as tested in the simulations. c, d Simulation predictions of the mean islet population pO₂ (c) and fraction of necrosis (d) of human islets encapsulated at variable densities in the SONIC spiral device (n = 3) and the scaffold-free control device (n = 3); mean ± SD; c: ****p < 0.0001 (control device versus SONIC spiral device at all islet densities); d: ***p = 0.0004 (control device versus SONIC spiral device at 4% islet density), **p = 0.0018 (control device versus SONIC spiral device at 6%), ****p < 0.0001 (control device versus SONIC spiral device at 8% and 10% islet densities). Statistical tests in c and d were analyzed via a two-way ANOVA followed by Sidak’s post hoc p-value adjustment for multiple comparisons. e, f Surface plots of pO₂ gradients (right) at selected cross-sections (left; labelled A-A, B-B, and C-C) in the control device (e) and the SONIC spiral device (f) at 8% human islet loading density showing significantly higher pO₂ and negligible necrosis in the SONIC spiral device compared to the control device (white regions in the islets represent necrosis, and yellow arrows in C-C section indicate necrosis even in some small islets).