Did you know that blood can only be stored for up to 6 weeks when refrigerated? Because synthetic blood is not available in the clinic, blood supplies must be continually replenished from healthy donors. Even if there is a surge in blood donations at one point in time, 6 weeks later there could be shortages if continued donations do not meet the current demand. Blood can be frozen for a decade or more but significant challenges in processing blood for frozen storage limit this option to specific situations such as for rare blood types or military use. The freezing process currently utilizes high concentrations of glycerol to protect red blood cells during frozen storage but this compound must be removed prior to transfusion, and the de-glycerolization process is very sensitive and time-consuming. Therefore, most hospitals and medical centers utilize refrigeration for blood storage.

What if, instead of refrigerating or freezing blood, there was a method to freeze-dry blood for long-term storage as a dry powder, similar to the process used for astronaut food? This could enable long-term blood storage at room temperature, and when the blood is needed for transfusion the cells could be quickly reconstituted simply by adding sterile water. Not only would this offer another option for long-term storage, it would be particularly useful in situations where refrigeration or freezing is not available, such as in some remote medical centers or for the military in far-forward settings. In addition, this method could enable stockpiles of strategic blood reserves in order to maintain an adequate blood supply during disasters such as hurricanes, which disrupt blood donations.

Electron microscopy image of red blood cells after drying/rehydration following ultrasound-mediated loading with preservative compounds.

The idea of turning blood into a dry powder and then rehydrating it for transfusion may sound like science fiction, but could it become a reality? Can nature provide clues to help us solve this problem? There are many cases in history where significant scientific breakthroughs were achieved by studying nature. For example, the Wright brothers studied the characteristics of birds’ wings during flight to discover an effective design for airplane wings. Also, Alessandro Volta invented the battery after carefully studying the electric organ in torpedo fish. In the context of cell preservation, it has been found that some organisms can survive complete desiccation for long periods of time. For example, tardigrades and brine shrimp (“water bears” and “sea monkeys”) can be dried out and remain in a state that approaches “suspended animation” for decades, but when they are rehydrated they return to normal physiological function and can even reproduce. This led us to ask the question, if these complex multicellular animals can survive desiccation, why not individual red blood cells? Scientists have found that these organisms produce protective compounds, including certain sugars and proteins, which prevent damage to their membranes during drying and rehydration.

Unfortunately, human cells do not have the transporters in their membranes that enable internalization of the protective compounds found in organisms that can survive desiccation. Therefore, an active loading method is required. We realized that the process of ultrasound-mediated drug delivery via sonoporation could potentially be applied to solve this problem and enable delivery of protective compounds into human red blood cells. In the past, most ultrasound research has either ignored red blood cells or attempted to minimize sonoporation in these cells. But what if we could intentionally sonoporate red blood cells outside of the body in order to actively load them with protective compounds so that they could be stored as a dry powder at room temperature until needed for transfusion?

Our initial efforts to load red blood cells with protective compounds for storage as a dry powder have been promising. We prepared solutions containing red blood cells, preservative compounds, and microbubbles followed by treatment with B-mode ultrasound for ~60 seconds. After ultrasound treatment, the cells were freeze-dried and stored as a dried powder at room temperature (21–23 °C) for 6 weeks or longer. Cells were rehydrated with water and we measured up to 30% recovery of viable red blood cells. In addition, we performed electron microscopy imaging of the rehydrated red blood cells and observed evidence of normal biconcave-discoid shape. Our next steps involve testing the rehydrated cells in an animal model of acute hemorrhage in order to assess the function and safety of the red blood cells in vivo after dry storage at room temperature.

Research studies are currently ongoing and much more work remains to be done before clinical translation is possible, but if it is successful this approach could have a significant impact on blood supply, particularly in locations where refrigeration and freezing are not available. In addition, this approach could potentially enable dry storage of other cell products. As I consider the possibilities of this approach, I wonder if there are other things that we can learn from nature that could also transform medical practice.

Have you learned something else from nature that has been incorporated into your medical practice? Do you have any ideas that could potentially transform medical practice? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Jonathan Kopechek is an Assistant Professor of Bioengineering at the University of Louisville. His Twitter handle is @ProfKope.