Gao Zhe, Namsrai Baterdene, Han Zonghu, Joshi Purva, Rao Joseph Sushil, Ravikumar Vasanth, Sharma Anirudh, Ring Hattie L, Idiyatullin Djaudat, Magnuson Elliott C, Iaizzo Paul A, Tolkacheva Elena G, Garwood Michael, Rabin Yoed, Etheridge Michael, Finger Erik B, Bischof John C
Department of Mechanical Engineering, University of Minnesota, 111 Church St. SE., Minneapolis, MN 55455, USA.
Department of Surgery, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Adv Mater Technol. 2022 Mar;7(3). doi: 10.1002/admt.202100873. Epub 2021 Oct 1.
To extend the preservation of donor hearts beyond the current 4-6 h, this paper explores heart cryopreservation by vitrification-cryogenic storage in a glass-like state. While organ vitrification is made possible by using cryoprotective agents (CPA) that inhibit ice during cooling, failure occurs during convective rewarming due to slow and non-uniform rewarming which causes ice crystallization and/or cracking. Here an alternative, "nanowarming", which uses silica-coated iron oxide nanoparticles (sIONPs) perfusion loaded through the vasculature is explored, that allows a radiofrequency coil to rewarm the organ quickly and uniformly to avoid convective failures. Nanowarming has been applied to cells and tissues, and a proof of principle study suggests it is possible in the heart, but proper physical and biological characterization especially in organs is still lacking. Here, using a rat heart model, controlled machine perfusion loading and unloading of CPA and sIONPs, cooling to a vitrified state, and fast and uniform nanowarming without crystallization or cracking is demonstrated. Further, nanowarmed hearts maintain histologic appearance and endothelial integrity superior to convective rewarming and indistinguishable from CPA load/unload control hearts while showing some promising organ-level (electrical) functional activity. This work demonstrates physically successful heart vitrification and nanowarming and that biological outcomes can be expected to improve by reducing or eliminating CPA toxicity during loading and unloading.
为了将供体心脏的保存时间延长至目前的4 - 6小时以上,本文探索了通过玻璃化 - 低温储存将心脏保存在类玻璃状态。虽然使用在冷却过程中抑制结冰的冷冻保护剂(CPA)使器官玻璃化成为可能,但在对流复温过程中会出现失败,原因是复温缓慢且不均匀,导致冰晶形成和/或破裂。在此探索了一种替代方法“纳米复温”,即通过血管系统灌注加载二氧化硅包覆的氧化铁纳米颗粒(sIONP),这使得射频线圈能够快速且均匀地使器官复温,以避免对流失败。纳米复温已应用于细胞和组织,一项原理验证研究表明在心脏中也是可行的,但仍缺乏适当的物理和生物学特征描述,尤其是在器官方面。在此,使用大鼠心脏模型,展示了对CPA和sIONP进行可控的机器灌注加载和卸载、冷却至玻璃化状态以及快速且均匀的纳米复温而不出现结晶或破裂。此外,经纳米复温的心脏在组织学外观和内皮完整性方面优于对流复温,与CPA加载/卸载对照心脏无差异,同时显示出一些有前景的器官水平(电)功能活性。这项工作证明了心脏玻璃化和纳米复温在物理上的成功,并且可以预期通过减少或消除加载和卸载过程中CPA的毒性来改善生物学结果。
Adv Mater Technol. 2022-3
Adv Sci (Weinh). 2021-10
Ann Biomed Eng. 2023-3
Cryo Letters. 2022
Adv Sci (Weinh). 2020-1-7
Sci Transl Med. 2017-3-1
Cryobiology. 2025-6
Clin Transplant Res. 2024-12-31
Front Transplant. 2023-6-8
Biomater Sci. 2024-7-23
Adv Healthc Mater. 2020-10
Adv Sci (Weinh). 2020-1-7
Am J Transplant. 2020-1
Magn Reson Med. 2020-5