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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.
Bibliographical noteFunding Information:
Z.G. and B.N. contributed equally to this work. E.B.F. and J.C.B. contributed equally as co‐senior authors. The authors thank Lakshya Gangwar for help with the fiber optic calibration, and Dr. Michael Etheridge for suggestions and discussions. The authors also thank UMN's Charfac Facility, Department of Earth Science, and Research Analytical Lab for providing instruments and assistance in characterization. The authors gratefully acknowledge the editorial assistance of Dr. Sarah Cook in the preparation of this manuscript. J.S.R. was supported by Schulze Diabetes Institute and Division of Transplantation at the Department of Surgery, University of Minnesota. The authors acknowledge Schulze Diabetes Institute, Department of Surgery for their confocal microscope and BioNet histology lab for tissue preparation. This work was funded by NIH R01 HL135046, R01 DK117425, and NSF EEC 1941543. The views, opinions, and findings contained in this report are those of the authors and should not be construed as an official Department of Army position, policy, or decision unless so designated by other documentation.
© 2021 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH
- iron oxide nanoparticle
- radio frequency warming
PubMed: MeSH publication types
- Journal Article
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- 1 Active
ATP-Bio: NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio)
9/1/20 → 8/31/25
Project: Research project