Alemdar Neslihan, Leijten Jeroen, Camci-Unal Gulden, Hjortnaes Jesper, Ribas Joao, Paul Arghya, Mostafalu Pooria, Gaharwar Akhilesh K, Qiu Yiling, Sonkusale Sameer, Liao Ronglih, Khademhosseini Ali
Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, United States.
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
ACS Biomater Sci Eng. 2017 Sep 11;3(9):1964-1971. doi: 10.1021/acsbiomaterials.6b00109. Epub 2016 Jun 20.
Oxygen is essential to cell survival and tissue function. Not surprisingly, ischemia resulting from myocardial infarction induces cell death and tissue necrosis. Attempts to regenerate myocardial tissue with cell based therapies exacerbate the hypoxic stress by further increasing the metabolic burden. In consequence, implanted tissue engineered cardiac tissues suffer from hypoxia-induced cell death. Here, we report on the generation of oxygen-generating hydrogels composed of calcium peroxide (CPO) laden gelatin methacryloyl (GelMA). CPO-GelMA hydrogels released significant amounts of oxygen for over a period of 5 days under hypoxic conditions (1% O). The released oxygen proved sufficient to relieve the metabolic stress of cardiac side population cells that were encapsulated within CPO-GelMA hydrogels. In particular, incorporation of CPO in GelMA hydrogels strongly enhanced cell viability as compared to GelMA-only hydrogels. Importantly, CPO-based oxygen generation reduced cell death by limiting hypoxia-induced necrosis. The current study demonstrates that CPO based oxygen-generating hydrogels could be used to transiently provide oxygen to cardiac cells under ischemic conditions. Therefore, oxygen generating materials such as CPO-GelMA can improve cell-based therapies aimed at treatment or regeneration of infarcted myocardial tissue.
氧气对细胞存活和组织功能至关重要。毫不奇怪，心肌梗死导致的局部缺血会引发细胞死亡和组织坏死。试图通过基于细胞的疗法来再生心肌组织会因进一步增加代谢负担而加剧缺氧应激。因此，植入的组织工程心脏组织会遭受缺氧诱导的细胞死亡。在此，我们报告了由负载过氧化钙（CPO）的甲基丙烯酰化明胶（GelMA）组成的产氧水凝胶的生成情况。在缺氧条件（1%氧气）下，CPO-GelMA水凝胶在5天多的时间里释放了大量氧气。释放的氧气被证明足以缓解包裹在CPO-GelMA水凝胶中的心脏侧群细胞的代谢应激。特别是，与仅含GelMA的水凝胶相比，在GelMA水凝胶中加入CPO可显著提高细胞活力。重要的是，基于CPO的产氧通过限制缺氧诱导的坏死减少了细胞死亡。当前研究表明，基于CPO的产氧水凝胶可用于在缺血条件下为心脏细胞短暂提供氧气。因此，诸如CPO-GelMA之类的产氧材料可改善旨在治疗或再生梗死心肌组织的基于细胞的疗法。
