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Bio-Design and Manufacturing  2022 Vol.5 No.2 P.265-276

http://doi.org/10.1007/s42242-021-00178-9


Development of a 3D subcutaneous construct containing insulin-producing beta cells using bioprinting


Author(s):  Chi B. Ahn, Ji-Hyun Lee, Joo H. Kim, Tae H. Kim, Hee-Sook Jun, Kuk H. Son & Jin W. Lee

Affiliation(s):  Department of Molecular Medicine, College of Medicine, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon, Republic of Korea; more

Corresponding email(s):   dr632@gilhospital.com, jwlee@gachon.ac.kr

Key Words:  3D bioprinting, Subcutaneous construct, Type 1 diabetes, Insulin, Beta cells


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Chi B. Ahn, Ji-Hyun Lee, Joo H. Kim, Tae H. Kim, Hee-Sook Jun, Kuk H. Son & Jin W. Lee . Development of a 3D subcutaneous construct containing insulin-producing beta cells using bioprinting[J]. Journal of Zhejiang University Science D, 2022, 5(2): 265-276.

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Abstract: 
type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of Langerhans. In severe cases, islet transplantation into the portal vein is performed. However, due to the loss of transplanted islets and the failure of islet function, the 5-year insulin independence rate of these patients is < 50%. In this study, we developed a long-term, insulin-secreting, 3D-bioprinted construct implanted subcutaneously with the aim of preventing islet loss. The bioprinted construct was fabricated by the multi-layer bioprinting of beta-cell (mouse insulinoma-6: MIN-6)-encapsulated alginate bioink and poly(caprolactone) biodegradable polymer. A glucose response assay revealed that the bioprinted constructs proliferated and released insulin normally during the 4-week in vitro period. Bioprinted MIN-6 generated clusters with a diameter of 100–200 µm, similar to the original pancreatic islets in the construct. In an in vivo study using type 1 diabetes mice, animals implanted with bioprinted constructs showed three times higher insulin secretion and controlled glucose levels at 8 weeks after implantation. Because the implanted, bioprinted constructs had a positive effect on insulin secretion in the experimental animals, the survival rate of the implanted group (75%) was three times higher than that of the non-implanted group (25%). The results suggest that the proposed, 3D-bioprinted, subcutaneous construct can be a better alternative to portal vein islet transplantation.

韩国嘉泉大学Kuk H. Son等 | 生物打印开发含有产生胰岛素的β细胞的3D皮下植入物

本研究论文聚焦生物3D打印胰岛对I型糖尿病的治疗研究。I型糖尿病是由朗格汉斯胰岛β细胞缺失引起的胰岛素缺乏导致的。在严重的情况下,一般会将胰岛移植到门静脉中。然而,由于移植胰岛的丧失和胰岛功能的衰竭,这些患者的5年胰岛素独立率小于50%。在这项研究中,我们开发了一种长期促进胰岛素分泌的3D生物打印结构,植入皮下以防止胰岛丢失。采用β细胞(小鼠胰岛素瘤-6:MIN-6)包封海藻酸盐生物墨水和聚己内酯生物降解聚合物的多层生物打印结构。葡萄糖反应测定显示,该结构在4周的体外培养期间可以正常增殖和释放胰岛素。生物打印的MIN-6细胞会聚集成为直径为100-200 μm的簇,类似于所打印结构的原始胰岛。本研究采用患有I型糖尿病的小鼠模型进行体内研究,植入生物打印结构的动物在术后8周显示出胰岛素分泌水平提高三倍并可以控制血糖水平。由于植入的生物打印结构对实验动物的胰岛素分泌有积极影响,因此植入组(75%)的存活率是对照组(25%)的三倍。结果表明,本文所提出的3D生物打印的皮下结构可能是比门静脉胰岛移植的更好替代方案。

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