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3D 生物打印海藻酸钠/甲基纤维素水凝胶混合物中的功能性胰岛。

3D Bioprinting of Functional Islets of Langerhans in an Alginate/Methylcellulose Hydrogel Blend.

机构信息

Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Hospital Carl Gustav Carus of Technische Universität Dresden and German Centre for Diabetes Research, Dresden, Tatzberg 47-49, 01307, Dresden, Germany.

出版信息

Adv Healthc Mater. 2019 Apr;8(7):e1801631. doi: 10.1002/adhm.201801631. Epub 2019 Mar 5.

Abstract

Transplantation of pancreatic islets is a promising strategy to alleviate the unstable blood-glucose control that some patients with diabetes type 1 exhibit and has seen many advances over the years. Protection of transplanted islets from the immune system can be accomplished by encapsulation within a hydrogel, the most investigated of which is alginate. In this study, islet encapsulation is combined with 3D extrusion bioprinting, an additive manufacturing method which enables the fabrication of 3D structures with a precise geometry to produce macroporous hydrogel constructs with embedded islets. Using a plottable hydrogel blend consisting of clinically approved ultrapure alginate and methylcellulose (Alg/MC) enables encapsulating pancreatic islets in macroporous 3D hydrogel constructs of defined geometry while retaining their viability, morphology, and functionality. Diffusion of glucose and insulin in the Alg/MC hydrogel is comparable to diffusion in plain alginate; the embedded islets continuously produce insulin and glucagon throughout the observation and still react to glucose stimulation albeit to a lesser degree than control islets.

摘要

胰岛移植是一种有前途的策略,可以缓解一些 1 型糖尿病患者血糖控制不稳定的问题,近年来已经取得了许多进展。通过将胰岛包裹在水凝胶中,可以实现对移植胰岛的免疫保护,其中研究最多的是海藻酸盐。在这项研究中,胰岛包封与 3D 挤出生物打印相结合,3D 挤出生物打印是一种增材制造方法,可用于制造具有精确几何形状的 3D 结构,从而生产出具有嵌入式胰岛的大孔水凝胶结构。使用可绘图的水凝胶混合物,由临床批准的超纯海藻酸盐和甲基纤维素(Alg/MC)组成,可在具有定义几何形状的大孔 3D 水凝胶结构中包封胰岛,同时保持其活力、形态和功能。葡萄糖和胰岛素在 Alg/MC 水凝胶中的扩散与在普通海藻酸盐中的扩散相当;嵌入的胰岛在整个观察过程中持续产生胰岛素和胰高血糖素,并且仍然对葡萄糖刺激有反应,尽管反应程度低于对照胰岛。

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