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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated,oxygen-generating biomaterials
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Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated,oxygen-generating biomaterials

机译:通过水解激活的产氧生物材料防止低氧诱导的β细胞和胰岛细胞死亡

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摘要

A major hindrance in engineering tissues containing highly metabolically active cells is the insufficient oxygenation of these implants, which results in dying or dysfunctional cells in portions of the graft. The development of methods to increase oxygen availability within tissue-engineered implants, particularly during the early engraftment period, would serve to allay hypoxiainduced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated solid calcium peroxide, PDMS-CaO_2. Encapsulation of solid peroxide within hydrophobic PDMS resulted in sustained oxygen generation, whereby a single disk generated oxygen for more than 6 wk at an average rate of 0.026 mM per day. The ability of this oxygen-generating material to support cell survival was evaluated using a β cell line and pancreatic rat islets. The presence of a single PDMS-CaO_2 disk eliminated hypoxia-induced cell dysfunction and death for both cell types, resulting in metabolic function and glucose-dependent insulin secretion comparable to that in normoxic controls. A single PDMS-CaO_2 disk also sustained enhanced p cell proliferation for more than 3 wk under hypoxic culture conditions. Incorporation of these materials within 3D constructs illustrated the benefits of these materials to prevent the development of detrimental oxygen gradients within large implants. Mathematical simulations permitted accurate prediction of oxygen gradients within 3D constructs and highlighted conditions under which supplementation of oxygen tension would serve to benefit cellular viability. Given the generality of this platform, the translation of these materials to other cell-based implants, as well as ischemic tissues in general,is envisioned.
机译:在含有高代谢活性细胞的工程组织中的主要障碍是这些植入物的氧合不足,这会导致移植物部分的细胞死亡或功能失调。开发增加组织工程植入物内的氧利用率的方法,尤其是在早期植入期间,将有助于减轻低氧诱导的细胞死亡。在这里,我们设计并开发了一种水解活化的产氧生物材料,其形式为聚二甲基硅氧烷(PDMS)包裹的固体过氧化钙PDMS-CaO_2。固体过氧化物在疏水性PDMS中的包封导致持续的氧气生成,从而单个磁盘以每天平均0.026 mM的速度生成6 wk以上的氧气。使用β细胞系和胰腺大鼠胰岛评估了这种产生氧气的物质支持细胞存活的能力。单个PDMS-CaO_2盘的存在消除了两种细胞类型的低氧诱导的细胞功能障碍和死亡,从而产生了与正常氧对照组相当的代谢功能和葡萄糖依赖性胰岛素分泌。在缺氧培养条件下,单个PDMS-CaO_2盘在3周内也能持续增强p细胞增殖。将这些材料并入3D构造中说明了这些材料在防止大型植入物中有害的氧气梯度发展方面的优势。数学模拟可以准确预测3D构造中的氧梯度,并强调了补充氧张力可有益于细胞活力的条件。考虑到该平台的普遍性,可以设想将这些材料翻译成其他基于细胞的植入物以及一般的缺血组织。

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  • 作者单位

    Diabetes Research Institute and Departments of University of Miami, Miami, FL 33136,Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33134;

    Diabetes Research Institute and Departments of University of Miami, Miami, FL 33136,Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33134;

    Diabetes Research Institute and Departments of University of Miami, Miami, FL 33136,Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33134;

    Diabetes Research Institute and Departments of University of Miami, Miami, FL 33136,Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33134,Surgery University of Miami, Miami, FL 33136,Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136;

    Diabetes Research Institute and Departments of University of Miami, Miami, FL 33136,Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33134,SurgeryUniversity of Miami, Miami, FL 33136;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    tissue engineering; encapsulation; bioartificial pancreas; diabetes;

    机译:组织工程;封装生物人工胰腺糖尿病;

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