In emergency medicine, time is oxygen—and blood loss remains the number one cause of death in trauma patients under 46. The problem? Traditional blood transfusions rely on donor supply, cold storage, and logistical infrastructure that simply doesn’t exist in many critical settings. Now, a team led by Dipanjan Pan at Penn State believes they may have a fix: freeze-dried synthetic blood that mimics not just the function but also the form of natural red blood cells.

Funded by a five-year, $2.7 million grant from the National Heart, Lung, and Blood Institute, Pan’s team is developing Nano-RBC—a deformable, nanoparticle-based red blood cell substitute loaded with hemoglobin, the oxygen-carrying protein in real blood. Unlike previous artificial blood attempts that often failed due to toxicity or poor oxygen delivery, Nano-RBC aims to replicate both the shape and oxygen transport behavior of native cells.

“Mother nature is hard to mimic, but we’re getting closer,” said Pan, the Dorothy Foehr Huck & J. Lloyd Chair Professor in Nanomedicine. “Our goal is to design and optimize a blood substitute prototype that is similar in shape to red blood cells and incorporates high-per-particle payloads of hemoglobin.”

That shape isn’t just aesthetic. It’s functional. The team’s Nano-RBCs are designed with a high surface-to-volume ratio and a biconcave, donut-like geometry—just like human erythrocytes—to enhance biological interaction, reduce immune response, and improve oxygen delivery efficiency. Remarkably, these synthetic cells are one-tenth the size of natural red blood cells but can carry equivalent hemoglobin loads.

From ErythroMer to Nano-RBC: Building the Future of Blood

This isn’t Pan’s first dive into artificial blood. Over the past decade, his team developed ErythroMer, a nanoparticle-based blood substitute that emulates red blood cell physiology. With over $14 million in funding from agencies including the NIH and the Department of Defense, the technology advanced to late-stage animal trials and helped launch KaloCyte, Inc., a startup co-founded by Pan, Allan Doctor (University of Maryland School of Medicine), and Philip Spinella (University of Pittsburgh).

ErythroMer’s standout feature? Lyophilization—the ability to freeze-dry the product for room-temperature storage and reconstitution with saline. That same property will be carried over to Nano-RBC, making the product ideal for field hospitals, remote areas, and crisis zones where traditional blood storage is impossible.

“Artificial blood is described as the ‘Holy Grail’ of trauma medicine,” said Pan. “Researchers have been battling to develop it for 150 years, with many failures along the way.”

Earlier generations of synthetic blood were plagued by complications—from poor oxygen release in hypoxic tissues to toxic iron overload. Pan’s team is designing Nano-RBC to sidestep those pitfalls, combining insights from past research with new computational modeling and materials science.

The project is highly interdisciplinary, with collaborators including Allan Doctor (oxygen release mechanisms), Paul Buehler (biodistribution), and Narayana Aluru at the University of Texas at Austin (computational modeling and design optimization). Together, they aim to create a next-gen oxygen therapeutic that’s safe, scalable, and shelf-stable.

“The inventiveness of materials researchers in health and medicine is limitless,” Pan said. “And we’re demonstrating that in this ambitious and highly collaborative project.”