Soft Liquid Metal Nanoparticles as Superior Ice-Growth Inhibitors Achieving Reduced Crystal Nucleation and Ultrarapid Rewarming for Cryopreservation

Abstract

High warming rates during cryopreservation are crucial and essential for successful vitrification. However, realizing faster warming rate in low concentration cryoprotective agents appears to be challenging for conventional warming process via convective heat transfer. Here a liquid metal nanosystem which can act as a spatial source to significantly enhance the warming rates with near-infrared laser irradiation during warming process is developed. It demonstrates that the synthetic Pluronic F127-liquid metal nanoparticles (PLM NPs) displayed multiple performances with uniform particle size, superior photothermal conversion efficiency (52%), repeatable photothermal stability, and low cytotoxicity. Specifically, liquid PLM NPs with less surface free energy are more difficult to form crystal nucleation compared with other solid NPs such as gold and Fe₃O₄, which is beneficial for the cooling process during cryopreservation. The viability of human bone marrow derived mesenchymal stem cells post-cryopreservation reached 77.9±3.4% which is 3-fold higher than that obtained by conventional warming method (25.3±6.43%). Additionally, the cells post-cryopreservation maintained their normal attachment, proliferation, surface marker expression and intact multilineage differentiation properties. Moreover, the results of mouse tails cryopreservation showed relatively improved intact structure when using PLM NPs rewarming compared with convective warming. The new liquid metal nanosystem provides a universal platform for cryopreservation that is expected to have widespread applications, especially the potential in bioengineering, cell-based medicine and clinical translation.