“We have assembled an outstanding team to develop a bio-synthetic whole-blood product that can be freeze-dried for easy portability, storage, and reconstitution,” said study principal investigator Allan Doctor, MD, Professor of Pediatrics and Director of the Center for Blood Oxygen Transport and Hemostasis (CBOTH) at UMSOM. “It will be designed for easy use in the field by medics at the point of injury, and will perform like a traditional blood transfusion to, for example, stabilize a patient’s blood pressure or facilitate blood clotting.”
To achieve this goal, the program will employ sophisticated artificial intelligence, state-of-the-art experimental platforms, and multiple complementary animal models. The product will be tested for efficacy and safety in trauma victims who have complex multiple injuries including shock and traumatic brain injury.
Bleeding is the most common cause of potentially survivable death in trauma, in both military and civilian settings. Whole blood transfusions remain the gold standard but present logistical challenges such as the dependence on available donors, the requirement for cold storage, and the limited viability of about 40 days. Rapid evacuation of patients who are rapidly bleeding out due to a gunshot wound or other trauma is not always an option. For this reason, there is an urgent need for an artificial blood product with a long shelf life that is easy to transport.
To conduct this project, Dr. Doctor has assembled a consortium comprising faculty members from UMSOM and UMSOP to work on the artificial oxygen carrier (red blood cell) component that he pioneered in earlier studies and on pharmacology, computational modeling, and machine learning to optimize the combined product, which will also include synthetic platelets and freeze-dried plasma.
This product will consist of ErythroMer, the artificial blood product made by KaloCyte, a company co-founded by Dr. Doctor in 2016 with bioengineer and synthetic chemist Dipanjan Pan, Ph.D., MSc, professor in nanomedicine at Penn State University, and Philip Spinella, MD, a military transfusion medicine expert at the University of Pittsburgh.
It will also include a synthetic platelet product developed by Anirban Sen Gupta, Ph.D. of Case Western Reserve University that is under development by Haima Therapeutics, and a freeze-dried plasma product made by Telefex.
Dr. Doctor is a founding partner, Chief Scientific Officer, and Chair of the Board of Directors for KaloCyte, which could potentially benefit from this research. His interest in the company has been reviewed in accordance with the university’s conflicts of interest policy to ensure objectivity in the research.
“We are well-positioned to support this highly complex project that requires the use of advanced modeling and simulation, and a scientific machine learning software system to optimize the prototypes and to test for safety and efficacy in models of complex trauma with multiple complications,” said the study co-investigator Joga Gobburu, Ph.D., MBA, Professor of Practice, Sciences, and Health Outcomes Research, and Director of the Center for Translational Medicine at UMSOP.
The first phase of the study will be to integrate multiple bio-artificial and synthetic components to deliver oxygen, stop bleeding, and replace volume; these are key therapeutic functions of whole blood in resuscitation. In the second phase, the team will evaluate efficacy and safety in increasingly complex and realistic trauma models. This phase will also involve developing strategies for stabilizing the product for months under ambient climate conditions in extreme environments.
Throughout both phases, the team will also plan, develop, and refine manufacturing methods. This will address the real-world pragmatic challenges of production, scaling, packaging, and quality control that must be surmounted to enable the effective transition of the developed products to successful clinical trials and, eventually, to safe and efficient clinical utility.
While UMSOM and UMSOP will be leading this effort, the consortium also includes leading scientists and complimentary experts from Case Western Reserve University, Charles River Laboratories, Latham Biopharm Group, Ohio State University, Pumas-AI Inc., Southwest Research Institute, University of California San Diego, University of Pittsburgh, Oregon Health Sciences University, the University of Texas Austin and the University of North Carolina, in addition to the companies developing the bio-synthetic blood components themselves: Haima Therapeutics, KaloCyte, and Teleflex.
“About 20,000 Americans each year bleed to death before they can be brought to the hospital. Transfusion at the point of injury is required to stablilize them and limit other organ injury,” said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. “This project will utilize cutting edge technologies like artificial intelligence to predict interactions among the blood components in various trauma model systems, which would not have been possible a decade ago.”
DARPA’s Fieldable Solutions for Hemorrhage with bio-Artificial Resuscitation Products (FSHARP) program aims to develop a field-deployable, shelf-stable whole blood equivalent that can be used to resuscitate trauma patients when donated blood products are not available. Other subcontractors have the potential to join the consortium pending the exercise of additional options in the FSHARP award.
