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Ultrasound for rapid and uniform rewarming of large volumes of cells and tissues after cryopreservation

Funder: UK Research and InnovationProject code: MR/T019166/1
Funded under: FLF Funder Contribution: 1,074,470 GBP

Ultrasound for rapid and uniform rewarming of large volumes of cells and tissues after cryopreservation

Description

Over 120,000 people in the USA and over 6000 people in the UK are waiting for organ transplants, and many more are suffering from organ failure. Many donor organs are not transplanted (approximately 60% of donor hearts and 20% of kidneys are not used), often because they can only be kept for a short time. Long term preservation would mean better matching with recipients over larger geographical areas, reducing the chances of rejection and increasing the number of organs that could be used. One potentially transformative method of preserving organs for a longer time is cryopreservation. This involves freezing the organs at very low temperatures and then defrosting them when needed. However, this is currently limited to small volumes (<3 ml), largely due to the difficulty in rewarming the tissues without damage after freezing. To avoid damage on rewarming, tissues must be heated quickly and uniformly. This is not possible with existing water bath methods so the development of new methods for volumetric rewarming of large tissue volumes is critical. The aim of this fellowship is to develop a novel method of tissue rewarming using ultrasound. As ultrasound passes through frozen tissue, it loses energy which is deposited as heat. By controlling the pattern of the ultrasound waves entering the tissue, heat can be deposited as needed to raise the temperature of the tissue quickly and uniformly. First, the ultrasound parameters will be optimised for maximum cell viability and optimal heating rate using small volumes of cells. An ultrasound array based on these parameters will then be developed with methods of steering and shaping the acoustic field to uniformly and rapidly heat larger volumes of cells. This will be extended to warming tissues with inhomogeneous acoustic and thermal properties and larger volumes, using real time feedback to control the heating distribution, with the ultimate vision of creating a fully flexible tool that can be used to rewarm whole organs. Ultrasonic volumetric warming has the potential to enable long-term storage of tissues and organs which would transform the availability of organs for transplant. It would also have many other applications such as increasing access to therapies involving implanting cells and tissues in the body for diseases such as type 1 diabetes or for restoration of fertility after cancer therapy.

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