New Warming Breakthrough for Cryopreserved Organs?
Although not of immediate concern to cryonics, warming has always been more of a challenge than cooling for cryopreservation by vitrification. This is because the initial formation of ice crystals is most rapid at very low temperature, such as -120°C, but crystal growth is faster at warmer temperatures. Tissue being warmed from the very cold temperatures of vitrification therefore often contains many tiny crystals that are ready to grow during passing through warmer temperatures until the melting point is reached. The warming rate required for successful recovery from vitrification therefore tends to be about ten times faster than the minimum cooling rate.
Since Fahy first proposed vitrification for organ cryopreservation in the 1980s, it was envisioned that a technique called radiofrequency warming (RF warming) would be used to recover organs from vitrification. In RF warming, a rapidly oscillating electric field at a frequency ranging from tens to hundreds of megahertz is applied during warming. The oscillating electric field causes water molecules to vibrate and heat the organ uniformly from the inside similar to a microwave oven. However RF warming uses frequencies much lower than microwave ovens to achieve more uniform heating without “hot spots.” Ruggera and Fahy at the U.S. FDA and American Red Cross published the first paper specifically studying RF warming of vitrified organs in 1990. In the decade that followed, Pegg, Evans and their research group at Cambridge University published numerous papers on technical aspects of RF warming of organs. In 2013 Wowk, Corral and Fahy resumed development of RF warming for recovery of organs from vitrification at 21st Century Medicine, Inc.
In 2014 Etheridge and Bischof et al at the University of Minnesota published a new idea for warming of vitrified organs. Magnetic nanoparticles were to be added to the cryoprotectant solution inside blood vessels, and the nanoparticles warmed by a radiofrequency magnetic field instead of electric field. This new method, called “nanowarming,” received a great deal of publicity in March of this year in connection with a new paper about it in the journal Science Translational Medicine. While having the disadvantage of warming occurring only in blood vessels, which could cause overheating of very large blood vessels, the method has a distinct advantage over classical RF warming. The energy absorption efficiency, and therefore heating efficiency, of classical RF warming varies with viscosity and temperature of tissue. This can be used beneficially to maximize warming rates during the most critical phases of rewarming. However classical RF warming is unavoidably inefficient at very low temperatures, below -100°C.
Nanowarming, in contrast, warms smoothly and efficiently at all temperatures, even the very lowest. Nanowarming may therefore be especially useful for uniform warming through the “glass transition” – the very low temperature at which vitrified organs change from being solid to liquid in their behavior – a critical phase of warming for avoiding thermal stress injuries.
With the development of nanowarming, there are now two independent technologies for achieving the necessary rapid warming of organs from the vitrified state, bringing us closer to an era of transplantable organ banking. The relevance of these technologies to cryonics remains speculative at this stage. In one envisioned resuscitation scenario, repairs of the brain and/or body would be conducted at cryogenic temperatures. It is reasonable to assume that these molecular machines would also introduce novel (ice-blocking) technologies that completely eliminate the risk of ice formation upon re-warming.
Another concern is cost. At this point adding high-quality nanoparticles to the perfusate would be prohibitively expensive.
This column was written with extensive input from a notable cryobiology researcher.
Originally published as a column in Cryonics magazine, July-August, 2017