Inductive heating of Magnetic Nanoparticles enables safe thawing of cryopreserved transplant organs

A new study reveals that nanotechnology can be used to rapidly rewarm cryogenically treated samples without damaging delicate frozen tissues, which may someday help make organ cryopreservation a reality. More than 60% of the hearts and lungs donated for transplantation must be discarded annually, because these tissues cannot be kept on ice for longer than four hours. According to recent estimates, if only half of unused organs were successfully transplanted, transplant waiting lists could be eliminated within two years. Long-term preservation methods like vitrification – which involves super-cooling biological samples to a glassy state – could establish tissue storage banks and reduce transplant rejection rates, greatly facilitating the process to find matching donors when needed.

* we have been able to vitrify organs since the 1980s but have not been able to safely thaw them
* we need to evenly and rapidly heat cryopreserved organs
* microwaving leaves hotspots that damage thawed organs
* magnetic nanoparticles enable the necessary rapid heating (100 degrees per minute) but without hotspots

Unlike convective warming, the new nanowarming method prevents tissue damage by evenly reheating cryogenically preserved tissues. This material relates to a paper that appeared in the March 1 2017 issue of Science, published by AAAS. The paper, by N. Manuchehrabadi at University of Minnesota in Minneapolis, MN, and colleagues was titled, “Improved tissue cryopreservation using inductive heating of magnetic nanoparticles.” CREDIT Manuchehrabadi et al., Science Translational Medicine (2017)

Science Translational Medicine – Improved tissue cryopreservation using inductive heating of magnetic nanoparticles

Unfortunately, while sophisticated cryopreservation methods exist to keep samples cold, tissues often suffer damage and even crack during the thawing process. Navid Manuchehrabadi and colleagues developed a unique approach to quickly warm up frozen tissues without compromising their cellular viability. The researchers mixed silica-coated iron oxide nanoparticles into a solution and generated uniform heat throughout the samples by applying an external magnetic field. After rewarming, none of the tissues displayed signs of harm, unlike control samples rewarmed slowly over ice. What’s more, the nanoparticles were successfully washed away from the sample following thawing. The scientists also tested their set-up using frozen human skin cells, segments of pig heart tissue, and sections of pig arteries in larger-sized volumes amounting to 50 milliliters. Although scaling up the system to accommodate whole organs will require further optimization, the authors say the technology might be applied beyond cryogenics, including delivering lethal pulses of heat to cancer cells.

Improved tissue cryopreservation with nanowarming

Organ transplantation is limited by the availability of viable donor organs. Although storage at very low temperatures (cryopreservation) could extend the time between organ harvest and transplant, the current gold standard for rewarming (convection) leads to cracking and crystallization in samples larger than a few milliliters. Manuchehrabadi et al. demonstrate the rewarming of cells and tissues by radiofrequency inductive heating using magnetic nanoparticles suspended in a cryoprotectant solution. This nanowarming technique rapidly and uniformly rewarmed cryopreserved fibroblasts, porcine arteries, and porcine heart tissues in systems up to 50 ml in volume, yielding tissues with higher viability than convective rewarming.

Abstract
Vitrification, a kinetic process of liquid solidification into glass, poses many potential benefits for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue matching for transplantation. To date, however, successful rewarming of tissues vitrified in VS55, a cryoprotectant solution, can only be achieved by convective warming of small volumes on the order of 1 ml. Successful rewarming requires both uniform and fast rates to reduce thermal mechanical stress and cracks, and to prevent rewarming phase crystallization. We present a scalable nanowarming technology for 1- to 80-ml samples using radiofrequency-excited mesoporous silica–coated iron oxide nanoparticles in VS55. Advanced imaging including sweep imaging with Fourier transform and microcomputed tomography was used to verify loading and unloading of VS55 and nanoparticles and successful vitrification of porcine arteries. Nanowarming was then used to demonstrate uniform and rapid rewarming at >130°C/min in both physical (1 to 80 ml) and biological systems including human dermal fibroblast cells, porcine arteries and porcine aortic heart valve leaflet tissues (1 to 50 ml). Nanowarming yielded viability that matched control and/or exceeded gold standard convective warming in 1- to 50-ml systems, and improved viability compared to slow-warmed (crystallized) samples. Last, biomechanical testing displayed no significant biomechanical property changes in blood vessel length or elastic modulus after nanowarming compared to untreated fresh control porcine arteries. In aggregate, these results demonstrate new physical and biological evidence that nanowarming can improve the outcome of vitrified cryogenic storage of tissues in larger sample volumes.

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