Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials
Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials
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DOI：
10.1073/pnas.1113560109
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发表时间：
2012-03-13
影响因子：
11.1
通讯作者：
Stabler, Cherie L.
中科院分区：
文献类型：
--
作者：
Pedraza, Eileen;Coronel, Maria M.;Stabler, Cherie L.
在工程组织含有高代谢活性细胞的主要障碍是这些植入物的氧合不足，这导致在移植物的部分死亡或功能障碍的细胞。开发增加组织工程植入物内的氧可用性的方法，特别是在早期植入期间，将有助于减轻缺氧诱导的细胞死亡。在此，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）封装的固体过氧化钙，PDMS-CaO 2。在疏水性PDMS内的固体过氧化物的封装导致持续的氧气产生，其中单个盘以0.026 mM/天的平均速率产生氧气超过6周。使用β细胞系和胰腺大鼠胰岛评估这种产氧材料支持细胞存活的能力。单个PDMS-CaO2盘的存在消除了两种细胞类型的缺氧诱导的细胞功能障碍和死亡，导致代谢功能和葡萄糖依赖性胰岛素分泌与常氧对照相当。在低氧培养条件下，单个PDMS-CaO2盘也持续增强β细胞增殖超过3周。将这些材料纳入3D结构中说明了这些材料在防止大型植入物内形成有害氧梯度方面的益处。数学模拟允许准确预测3D结构内的氧梯度，并突出显示补充氧张力将有利于细胞活力的条件。考虑到该平台的一般性，设想将这些材料转化为其他基于细胞的植入物以及一般的缺血组织。
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 hypoxia-induced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated solid calcium peroxide, PDMS-CaO2. 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 beta cell line and pancreatic rat islets. The presence of a single PDMS-CaO2 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-CaO2 disk also sustained enhanced beta 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.