Physical vitrification and nanowarming at human organ scale to enable cryopreservation.

Organ banking by vitrification could revolutionize transplant medicine. However, vitrification and rewarming have never been demonstrated at the human organ scale. Using modeling and experimentation, we tested the ability to vitrify and rewarm 0.

Kidney tissue loading reduces the critical cooling and warming rates of VS55 and VMP cryoprotective solutions.

Critical cooling and warming rates (CCR and CWR) are two important calorimetric properties of cryoprotective agents (CPA) solutions, and achieving these rates is generally regarded as the critical criterion for successful vitrification and rewarming. In 1996, Peyridieu et al. discovered that the measured critical rates are reduced inside kidney tissue equilibrated with 30 % (w/w) 2,3-butanediol compared to its free CPA solution.

A Low-Cost, Tabletop LOD-EPR System for Nondestructive Quantification of Iron Oxide Nanoparticles in Tissues.

Iron oxide nanoparticles (IONPs) have wide utility in applications from drug delivery to the rewarming of cryopreserved tissues. Due to the complex behavior of IONPs (e.g.

CPA toxicity screening of cryoprotective solutions in rat hearts.

In clinical practice, donor hearts are transported on ice prior to transplant and discarded if cold ischemia time exceeds ∼5 h. Methods to extend these preservation times are critically needed, and ideally, this storage time would extend indefinitely, enabling improved donor-to-patient matching, organ utilization, and immune tolerance induction protocols. Previously, we demonstrated successful vitrification and rewarming of whole rat hearts without ice formation by perfusion-loading a cryoprotective agent (CPA) solution prior to vitrification.

Model-Guided Design and Optimization of CPA Perfusion Protocols for Whole Organ Cryopreservation.

Vitrification could enable long-term organ preservation, but only after loading high-concentration, potentially toxic cryoprotective agents (CPAs) by perfusion. In this paper, we combine a two-compartment Krogh cylinder model with a toxicity cost function to theoretically optimize the loading of CPA (VMP) in rat kidneys as a model system. First, based on kidney perfusion experiments, we systematically derived the parameters for a CPA transport loading model, including the following: V = 86.

Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model.

Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform.

Cryopreservation of Whole Rat Livers by Vitrification and Nanowarming.

Liver cryopreservation has the potential to enable indefinite organ banking. This study investigated vitrification-the ice-free cryopreservation of livers in a glass-like state-as a promising alternative to conventional cryopreservation, which uniformly fails due to damage from ice formation or cracking. Our unique "nanowarming" technology, which involves perfusing biospecimens with cryoprotective agents (CPAs) and silica-coated iron oxide nanoparticles (sIONPs) and then, after vitrification, exciting the nanoparticles via radiofrequency waves, enables rewarming of vitrified specimens fast enough to avoid ice formation and uniformly enough to prevent cracking from thermal stresses, thereby addressing the two main failures of conventional cryopreservation.