An Injectable Oxygen Release System to Augment Cell Survival and Promote Cardiac Repair Following Myocardial Infarction.

An Injectable Oxygen Release System to Augment Cell Survival and Promote Cardiac Repair Following Myocardial Infarction.
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可注射的氧气释放系统,可增强细胞存活并促进心肌梗塞后心脏修复。

DOI:
10.1038/s41598-018-19906-w
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发表时间:
2018-01-22
期刊:
影响因子:
4.6
通讯作者:
Guan J
Guan J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fan Z;Xu Z;Niu H;Gao N;Guan Y;Li C;Dang Y;Cui X;Liu XL;Duan Y;Li H;Zhou X;Lin PH;Ma J;Guan J

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心肌梗死(MI)后缺氧导致大量心脏细胞死亡。保护心脏细胞和促进心脏修复是关键的治疗目标。这些目标可以通过将氧气重新引入梗塞区域来实现。然而,目前的全身氧气输送方法不能有效地将氧气扩散到具有极低血流量的梗塞区域中。在这项工作中,我们开发了一种新的氧气输送系统,可以特异性地输送到梗死组织,并持续释放氧气以保护心肌细胞。该系统是基于一个热敏的,可注射和快速凝胶化水凝胶,和氧气释放微球。快速凝胶化水凝胶用于增加微球在心脏组织中的保留。该系统能够连续释放氧气4周。释放的氧气显着增加心肌细胞的存活率下的缺氧条件(1%O2)模仿的梗死心脏。在低氧条件下(1%O2),它也减少了肌成纤维细胞的形成。植入梗死心脏4周后,释放的氧气显著增加了细胞存活,降低了巨噬细胞密度,减少了胶原沉积和肌成纤维细胞密度,并刺激了组织血管生成,导致心脏功能显著增加。
Oxygen deficiency after myocardial infarction (MI) leads to massive cardiac cell death. Protection of cardiac cells and promotion of cardiac repair are key therapeutic goals. These goals may be achieved by re-introducing oxygen into the infarcted area. Yet current systemic oxygen delivery approaches cannot efficiently diffuse oxygen into the infarcted area that has extremely low blood flow. In this work, we developed a new oxygen delivery system that can be delivered specifically to the infarcted tissue, and continuously release oxygen to protect the cardiac cells. The system was based on a thermosensitive, injectable and fast gelation hydrogel, and oxygen releasing microspheres. The fast gelation hydrogel was used to increase microsphere retention in the heart tissue. The system was able to continuously release oxygen for 4 weeks. The released oxygen significantly increased survival of cardiac cells under the hypoxic condition (1% O2) mimicking that of the infarcted hearts. It also reduced myofibroblast formation under hypoxic condition (1% O2). After implanting into infarcted hearts for 4 weeks, the released oxygen significantly augmented cell survival, decreased macrophage density, reduced collagen deposition and myofibroblast density, and stimulated tissue angiogenesis, leading to a significant increase in cardiac function.
持续释放基于肽的基质金属蛋白酶 2 抑制剂可减轻心肌梗死后的不良心脏重塑并改善心脏功能
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