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胰腺α和β细胞中的氧化应激作为生物相容性生物材料的选择标准。

Oxidative stress in pancreatic alpha and beta cells as a selection criterion for biocompatible biomaterials.

机构信息

Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, the Netherlands.

Department of Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.

出版信息

Biomaterials. 2021 Jan;267:120449. doi: 10.1016/j.biomaterials.2020.120449. Epub 2020 Oct 24.

Abstract

The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets.

摘要

胰岛移植的临床成功率受到导致移植物失功的因素限制,这些因素包括炎症、急性缺血、急性期反应和血管化不足。缺血和血管化不足都会导致高水平的氧化应激,而胰岛包裹、炎症和不理想的细胞-生物材料相互作用进一步加重了这种情况。为了确定不会进一步增加破坏性氧化应激水平且适合制造胰岛包封设备的生物材料,我们研究了五种临床批准的聚合物对氧化应激和胰岛(α和β细胞)功能的影响。我们发现,300 聚(对苯二甲酸乙二酯)55/聚(对苯二甲酸丁二酯)45(PEOT/PBT300)比其他生物材料更不易断裂且更有弹性,这对于其免疫保护功能很重要。此外,它不会在 MIN6 β细胞系中诱导氧化应激或降低细胞活力,甚至在 7 天内促进保护性内源性抗氧化剂表达。重要的是,PEOT/PBT300 是我们研究的生物材料之一,它不会干扰人胰岛中的胰岛素分泌。

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