Heat-emitting nanoparticles enable organ reheating

A new technique that uses heat-emitting nanoparticles could enable doctors to reheat organs rapidly enough to prevent ice recrystallization, which cracks and destroys organs. If successful, the research could make it possible to routinely freeze and reuse donated kidneys, livers, and other organs the way physicians now do with blood.

The ability to bank organs solves a major problem. Each year in the United States, only 25% of people awaiting an organ transplant receive one.

This is not due to a lack of organ donors alone. A key barrier is time: Once doctors harvest an organ, they must transplant it within a few hours or it will deteriorate beyond use. Hearts, for example, last only four hours, which is why more than three out of five donated hearts never make it to a patient.

Being able to safely cryocool and warm organs for reuse would allow hospitals to store, ship, and use organs that are now thrown away. Hospitals could bank organs, match them more closely with recipients, and ship them further distances without worrying about degrading their viability.

True organ banking would also give hospitals the time to schedule transplants with the best possible surgical teams, instead of working against the clock to round up whatever physicians are available while the organ is still viable.

John C. Bischof, a professor of mechanical engineering at University of Michigan, hopes to make this possible.

He came to his work by a circuitous route. He originally wanted to destroy cancer cells by freezing. About 10 years ago, he began studying nanoparticles as a way to heat cells. Naomi Halas, a chemist at Rice University, pioneered a similar approach to heat and kill cancer tissues, which is now undergoing clinical testing.

Bischof, however, took his research in a different direction. He and his multidisciplinary team began to investigate how to use nanoparticles that absorb electromagnetic radiation and emit heat to restore cryocooled organs rapidly and uniformly.

Scientists have long been able to cryocool organs. After harvesting the organ, they immediately perfuse it with an antifreeze-like solution of chemicals called a cryopreservative. It spreads through the organ, filling even the smallest arterial and venal vessels. It suppresses the formation of ice crystals, which would otherwise expand within the solidifying organ and destroy the structure of its cells and tissues.

Only then do scientists rapidly drop the temperature to 160°C and 196°C. Chilling the organ rapidly works hand in glove with the cryopreservative to prevent formation of ice crystals. The process, which turns watery liquids in the organ turn into glasslike solids, is called vitrification.

Unfortunately, problems arise when researchers thaw the organ. If heating is too slow or uneven, the organ will linger in regions where ice recrystallizes despite the cryopreservative. The ice turns the delicate internal structure of the organs to mush.

Researchers have tried several methods to reheat organs to move rapidly past recrystallization temperatures. While powerful microwaves could reheat organs fast enough, they also created hot spots that burned and killed tissue.

Bischof thought he could address both heating speed and uniformity by adding iron oxide nanoparticles to the mix. When he suspended the nanoparticles in a liquid and subjected it to an alternating electromagnetic induction field, they vibrate fast enough to generate heat. In fact, they warm samples at rates of 100-200°C per minute, roughly 10 to 100 times faster than previous methods. Since he perfused the nanoparticles throughout the organ, the warming is also highly uniform.

Bischof patented the process, then worked with colleague Christy Hanes, a professor of chemistry at the University of Michigan, to coat the nanoparticles with silica to improve its biocompatibility.

The technology’s scalability gives it promise. “Once you accept that these nanoparticles can create a uniform heat-generation system inside of a system, it shouldn’t matter if it’s one milliliter or 50 milliliters or one full liter,” Bischof said “If we scale up the fields, we have essentially the same system.”

The group has shown that it can rethaw pig heart valves and blood vessels without any signs of damage, and wash the nanoparticles out of the blood stream when they were done. Bischof found no sign that the nanoparticles entered the organ’s cells.

The researchers are also tweaking the process, looking at how a range of cryopreservative compositions and vitrification temperatures interact with the nanoparticles. They are also exploring the best ways to perfuse nanoparticles into organs and wash them out.

Meanwhile, the team is currently working on rabbit kidneys and human donor skin, muscle, and blood vessels. Ultimately, it hopes to demonstrate that it can take a heart, infuse it with nanoparticles, and bring it back without damaging it, Bischof said.

While other researchers have vitrified, warmed, and implanted a functioning rabbit kidney, nobody has put vitrification solution into the heart, brought it back and transplanted it, Bischof said.

The research team members are on the verge of testing to see if they can freeze and warm hearts of rabbits without harming the organ and then transplant them into the animals.

“Everyone wants to be at the human stage, but we’re years away from that,” he said.

Still, Bischof’s research into rapid warming promises to move us closer to that goal, and to true organ banking.